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In the present work, the influence of a corrosive environment and temperature on the corrosion resistance properties of duplex stainless steel S31803 was evaluated. The corrosive process was carried out using solutions of 1.5% HCl (m/m) and 6% FeCl 3 (m/m), at temperatures of 25 and 50 °C. The microstructure of UNS S31803 duplex stainless steel is composed of two phases, ferrite and austenite, oriented in the rolling direction, containing a ferrite percentage of 46.2% in the rolling direction and 56.1% in the normal direction. Samples, when subjected to corrosive media and temperature, tend to decrease their mechanical property values. It was observed, in both corrosive media, that with increasing test temperature, there is an increase in the corrosion rate, both uniform and pitting. The sample in HCl solution obtained a uniform corrosion rate of 0.85% at 25 °C and 0.92% at 50 °C and pitting rates of 0.77% and 1.47% at the same temperatures, respectively. When tested in FeCl 3 solution, it obtained uniform corrosion of 0.0006% and 0.93% and pitting of 0.53% and 18.5%, at the same temperatures. A reduction in dissolution potentials is also noted, thus characterizing greater corrosion in the samples with increasing temperature.

Aim: This study evaluates the in vitro efficacy of 8-hydroxyquinoline (8HQ) derivatives in controlling the phytopathogenic fungus Phaeomoniella chlamydospora., Methods and Results: The in vitro tests assessed the susceptibility to the minimum inhibitory concentration (MIC), checkerboard assay, mycelial growth (MG) inhibition, and EC50 determination. Among the seven agricultural fungicides tested, tebuconazole (TEB) displayed the lowest MIC, 1.01 µg mL-1, followed by captan (CAP), thiophanate methyl (TM), and mancozeb with MICs of 4.06, 5.46, and 10.62 µg mL-1, respectively. The 8HQ derivatives used in this study were clioquinol and PH 151 (PH) with MICs of 1.09 and 2.02 µg mL-1, respectively. PH associated with TEB and CAP showed synergism and inhibited 95.8% of MG at the highest dose. TEB inhibited 100% of MG at the three highest doses, while associated with PH exhibited the lowest EC50 (0.863 + 0.0381 µg mL-1)., Conclusions: We concluded that the 8HQ derivatives tested controlled effectively the P. chlamydospora in vitro. PH associated with CAP and TEB exhibited a synergistic effect. The association between PH and TM was considered indifferent., Impact Statement: This study expands the list of active ingredients tested against P. chlamydospora, with the PH 151 and clioquinol derivatives being tested for the first time. The in vitro efficacy and synergistic action with other fungicides suggest a potential use as a grapevine wound protectant. This association makes it possible to reduce doses and increase the potency of both drugs, reducing the risk of resistance development and harm to humans and the environment., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

New-generation sequencing (NGS) techniques have brought the opportunity for genomic monitoring of several microorganisms potentially relevant to public health. The establishment of different methods with different mechanisms provides a wide choice, taking into account several aspects. With that in mind, the present aim of the study was to compare basic genomic sequencing metrics that could potentially impact genotyping by nanopores from Oxford Nanopore Technologies and by synthesis from Illumina in clinical samples positive for Chikungunya (CHIKV). Among the metrics studied, running time, read production, and Q score were better represented in Illumina sequencing, while the MinIOn platform showed better response time and greater diversity of generated files. That said, it was possible to establish differences between the studied metrics in addition to verifying that the distinctions in the methods did not impact the identification of the CHIKV virus genotype., (© 2023. Academy of Scientific Research and Technology.)

This study aimed to evaluate the yield, physical-chemical properties, fatty acid (FA) profile, and sensory traits of goat milk under different nutritional strategies in a Brazilian semiarid environment. Eighteen lactating crossbred dairy goats were distributed in a completely randomized design with three nutritional strategies: Caatinga strategy (1.5% of body weight with a concentrate supplementation), Corn-based confined strategy, and Spineless Cactus confined strategy. Daily milk yield was recorded, and milk samples were collected from all animals. Goats fed the spineless cactus-based diet presented a higher milk yield than goats feed the other strategies. Moreover, milk from goats fed with a spineless Cactus confined strategy presented higher saturated FA (SFA), and a lower proportion of cis- monounsaturated FA, trans-monounsaturated FA, and c9,t11-18:2 than milk from goats feed the other strategies. Milk from goats in the pasture system presented the highest proportions of 18:2n-6, 18:3n-3, and thus of polyunsaturated FA, when compared with milk from confined goats. We assume that milk from goats grazing in Caatinga pastures presents more benefits to human health due to the positive effects of this diet on the milk's fat content and FA profile, and this feeding strategy also results in a better sensory evaluation that may increase the acceptability of goat milk by consumers. All nutritional strategies evaluated herein and adopted in the semiarid region of Brazil are recommended for maintaining the yield, physical-chemical properties, and acceptability of milk goats., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Carbon dots (CDs) correspond to carbon-based materials (CBM) with sizes usually below 10 nm. These nanomaterials exhibit attractive properties such us low toxicity, good stability, and high conductivity, which have promoted their thorough study over the past two decades. The current review describes four types of CDs: carbon quantum dots (CQDs), graphene quantum dots (GQDs), carbon nanodots (CNDs), and carbonized polymers dots (CPDs), together with the state of the art of the main routes for their preparation, either by "top-down" or "bottom-up" approaches. Moreover, among the various usages of CDs within biomedicine, we have focused on their application as a novel class of broad-spectrum antibacterial agents, concretely, owing their photoactivation capability that triggers an enhanced antibacterial property. Our work presents the recent advances in this field addressing CDs, their composites and hybrids, applied as photosensitizers (PS), and photothermal agents (PA) within antibacterial strategies such as photodynamic therapy (PDT), photothermal therapy (PTT), and synchronic PDT/PTT. Furthermore, we discuss the prospects for the possible future development of large-scale preparation of CDs, and the potential for these nanomaterials to be employed in applications to combat other pathogens harmful to human health. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease., (© 2023 Wiley Periodicals LLC.)

Background: Since the muscles of chewing are involved in the region of the mandibular angle, important structures in surgical and orthodontic procedures, to study its morphological aspects and the possible influence of different patterns of skeletal development would be of interest. Thus, this study aimed to assess the influence of patient characteristics - such as sex, skeletal malocclusion (Class I, Class II, and Class III) and facial type (brachycephalic, mesocephalic, and dolichocephalic) - on the width, height, thickness, and volume of the mandibular angle, using cone-beam computed tomography (CBCT) scans., Methods: CBCT scans were assessed - 144 men and 154 women, total of 298 - and classified according to skeletal patterns (skeletal malocclusions and facial types). Width, height, and thickness of the mandibular angle were measured using OnDemand 3D software. The volumetric measures of the mandibular angle were obtained using the ITK-SNAP software. Analysis of Variance (multiway ANOVA) with Tukey's post-hoc test compared the data, with a 5% significance level., Results: Among the factors studied, sex significantly influenced all the analyzed variables (height, width, thickness, and volume of the mandibular angle) (p < 0.05); in general, male individuals presented higher values than females. In some cases, the skeletal malocclusion and facial type factors influenced only the width and height variables (p < 0.05); in general, the Class III and dolichocephalic individuals presented higher values in relation to the other types of skeletal malocclusions and facial types., Conclusions: Variations in the craniofacial growth pattern, considering the different skeletal malocclusions and facial types, had some influence in the width and height dimensions of the mandibular angle. Furthermore, sex influenced all the studied variables., (© 2023. The Author(s).)

In South Brazil, the incidence of pediatric adrenocortical carcinoma (ACC) is higher than in other regions and countries worldwide. The ACC treatment includes therapy with mitotane, the only adrenolytic drug approved by the FDA. The mitotane metabolism occurs via two main reactions: the β-hydroxylation, which yields the final product o,p'-DDA, and the α-hydroxylation, which will give the final product o,p'-DDE. It is speculated that o,p'-DDE may be an active metabolite since it has a cytotoxic effect on adrenocortical carcinoma cells (H295R). No further studies have been conducted to confirm this hypothesis; however, it was found that mitotane and its metabolites are present at significantly different concentrations in the plasma of the patients. Our study aimed to assess the in vitro effects of o,p'-DDE and o,p'-DDD in cell death pathways, oxidative parameters, and interaction with adrenal CYP's involved in the steroidogenic process in the H295R cell line. It was found that o,p'-DDE had a different effect than the o,p'-DDD on apoptosis, inhibiting this cell death pathway, but it promotes cell necrosis at higher concentrations. In contrast to o,p'-DDD, the o,p'-DDE did not have effects on the different oxidative parameters evaluated, but exhibited stimulatory interactions with steroidogenic CYP's, at intermediate concentrations. Therefore, we demonstrated important cell effects of o,p'-DDE; its plasma levels during mitotane therapy should be monitored as an important therapeutic parameter.

Competing Interests: None disclosed.

Background: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country., Methods: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil's most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning., Results: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5-21.2%) in Curitiba to 75.0% (95% CrI 70.8-80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43-3.53)., Conclusions: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread., Funding: This work was supported by Itaú Unibanco 'Todos pela Saude' program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Medicina; Programa Inova Fiocruz-CE/Funcap - Edital 01/2020 Number: FIO-0167-00065.01.00/20 SPU N°06531047/2020; JBS - Fazer o bem faz bem., Competing Interests: CP, LB, CW, TS, MO, RP, IM, LD, MB, NT, RF, VB, FM, AM, Cd, NS, SF, KF, Ld, LS, PI, LX, MC, NF, FA, LC, VP, MR, Rd, Sd, AC, MV, Md, EL, LF, SM, GN, AS, MB, MC, CD, OR, NF, VN, ES No competing interests declared, (© 2022, Prete, Buss, Whittaker et al.)

The plant Miconia albicans (Sw.) Triana has been popularly used in Brazil to treat chronic inflammatory disturbances, such as osteoarthritis. This disease affects 250 million people worldwide, and is associated with intense pain and loss of articular function. There is a lack of information about the phytochemistry and bioactivity of M. albicans . Therefore, this study determined the chemical composition of some extracts and evaluated their cytotoxicity, along with their antioxidant and anti-inflammatory, activities using in vitro models. Aqueous and ethanolic extracts were prepared. Afterwards, a liquid-liquid partition was developed using chloroform, ethyl acetate, and n -butanol. The extracts were characterized by LC-MS, and their biological activities were evaluated on epithelial cells (Vero), tumoral hepatic cells (Hep-G2), and THP-1 macrophages. LC-MS analyses identified several flavonoids in all fractions, such as quercetin, myricetin, and their glycosides. The crude extracts and n -butanol fractions did not present cytotoxicity to the cells. The non-toxic fractions presented significant antioxidant activity when evaluated in terms of DPPH scavenging activity, lipid peroxidation, and ROS inhibition. THP-1 macrophages treated with the n -butanol fraction (250 µg/mL) released fewer pro-inflammatory cytokines, even in the presence of LPS. In the future, it will be necessary to identify the phytochemicals that are responsible for anti-inflammatory effects for the discovery of new drugs. In vivo studies on M. albicans extracts are still required to confirm their possible mechanisms of action.

During the first semester of 2021, all of Brazil has suffered an intense wave of COVID-19 associated with the Gamma variant. In July, the first cases of Delta variant were detected in the state of Rio de Janeiro. In this work, we have employed phylodynamic methods to analyse more than 1 600 genomic sequences of Delta variant collected until September in Rio de Janeiro to reconstruct how this variant has surpassed Gamma and dispersed throughout the state. After the introduction of Delta, it has initially spread mostly in the homonymous city of Rio de Janeiro, the most populous of the state. In a second stage, dispersal occurred to mid- and long-range cities, which acted as new close-range hubs for spread. We observed that the substitution of Gamma by Delta was possibly caused by its higher viral load, a proxy for transmissibility. This variant turnover prompted a new surge in cases, but with lower lethality than was observed during the peak caused by Gamma. We reason that high vaccination rates in the state of Rio de Janeiro were possibly what prevented a higher number of deaths.

SARS-CoV-2 serologic surveys estimate the proportion of the population with antibodies against historical variants, which nears 100% in many settings. New approaches are required to fully exploit serosurvey data. Using a SARS-CoV-2 anti-Spike (S) protein chemiluminescent microparticle assay, we attained a semi-quantitative measurement of population IgG titers in serial cross-sectional monthly samples of blood donations across seven Brazilian state capitals (March 2021−November 2021). Using an ecological analysis, we assessed the contributions of prior attack rate and vaccination to antibody titer. We compared anti-S titer across the seven cities during the growth phase of the Delta variant and used this to predict the resulting age-standardized incidence of severe COVID-19 cases. We tested ~780 samples per month, per location. Seroprevalence rose to >95% across all seven capitals by November 2021. Driven by vaccination, mean antibody titer increased 16-fold over the study, with the greatest increases occurring in cities with the highest prior attack rates. Mean anti-S IgG was strongly correlated (adjusted R2 = 0.89) with the number of severe cases caused by Delta. Semi-quantitative anti-S antibody titers are informative about prior exposure and vaccination coverage and may also indicate the potential impact of future SARS-CoV-2 variants.

The immunopathology associated with Leishmaniasis is a consequence of inflammation. Upon infection with Leishmania , the type of host-immune response is determinant for the clinical manifestations that can lead to either self-healing or chronic disease. Multiple pathways may determine disease severity. A comparison of systemic immune profiles in patients with cutaneous leishmaniasis caused by L. guyanensis and healthy individuals with the same socio-epidemiological characteristics coming from the same endemic areas as the patients is performed to identify particular immune profile and pathways associated with the progression of disease development. Twenty-seven plasma soluble circulating factors were evaluated between the groups by univariate and multivariate analysis. The following biomarkers pairs IL-17/IL-9 (ρ=0,829), IL-17/IL-12 (ρ=0,786), IL-6/IL-1ra (ρ=0,785), IL-6/IL-12 (ρ=0,780), IL-1β/G-CSF (ρ=0,758) and IL-17/MIP-1β (ρ=0,754) showed the highest correlation mean among the patient while only INF-γ/IL-4 (ρ=0.740), 17/MIP-1β (ρ=0,712) and IL-17/IL-9 (ρ=0,707) exhibited positive correlation among the control group. The cytokine IL-17 and IL1β presented the greater number of positive pair correlation among the patients. The linear combinations of biomarkers displayed IP-10, IL-2 and RANTES as the variables with the higher discriminatory activity in the patient group compared to PDGF, IL-1ra and eotaxin among the control subjects. IP-10, IL-2, IL-1β, RANTES and IL-17 seem to be predictive value of progression to the development of disease among the Lg -infected individuals., 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 Mesquita, Junior, Silva, Silva, Araújo, Pinheiro, Kerr, Silva, Souza, Almeida, Queiroz, Souza, Silva, Sequera, Souza, Barbosa, Pontes, Guerra and Ramasawmy.)

Neuropathic and postoperative pain are clinical conditions that impair the patient's quality of life. The current pharmacotherapy of both painful states is ineffective and accompanied by several side effects. In order to develop new therapeutics targets, the secondary metabolites of plants have been extensively studied. Acmella oleracea ("jambu") is a native plant from the Amazon region and rich in alkylamides, bioactive compounds responsible for inducing anesthetic and chemesthetic sensations. We previously demonstrated that the intraplantar administration of an hexanic fraction (HF) rich in alkylamides from jambu and the synthetic isobutylalkyl amide (IBA) at 0.1 μg/20 μL can promote antinociceptive and anti-inflammatory effects. Thus, this study aimed to evaluate the local effect of HF and IBA (0.1 μg/20 μL) on neuropathic (partial sciatic nerve ligation, PSNL) and postoperative pain (plantar incision surgery, PIS) models in mice. Seven days after the PSNL, the mechanical (von Frey test) and cold (acetone-evoked evaporative cooling) allodynia, and digital gait parameters were analyzed. The intraplantar HF and IBA treatments attenuated the mechanical and cold allodynia as well as the static (max. Contact and print area) and dynamic (stand duration) parameters of digital gait analyses. On the day after PIS, the mechanical allodynia, heat hyperalgesia (hot plate, 52 ± 0.1°C), and spontaneous nociception scores were evaluated. Topical treatment with HF reduced the mechanical allodynia, heat hyperalgesia, and spontaneous nociception scores. In contrast, IBA treatment only partially reduced the mechanical allodynia. In summary, the local treatment with HF was effective on both neuropathic and postoperative pain, as opposed to IBA, which only had an effect on neuropathic pain., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Dengue, Zika, chikungunya, and yellow fever are arboviruses transmitted by Aedes aegypti mosquito. In this regard, a number of techniques have emerged aiming to combat its proliferation. Elimination of Aedes aegypti larvae by photodynamic action has been reported as an efficient approach. In this regard, this study was aimed at synthetize and characterize formulations with different proportions (w/w) of the plant-based photolarvicidal curcumin and d-mannitol (CCD 1-4) and their evaluation on sublethal photolarvicidal efficiency, photodegradation profile,solubility, internalization, elimination time, persistence in simulated field, growth of microorganisms in water and the toxicity using an animal models (Zebrafish). CCD 3 (curcumin:d-mannitol 50:50 w/w) showed the best efficacy (LC 50-24h  = 0.01 mg/L), and also presented the shortest internalization and longest elimination time, 60 min and 8 days, respectively. This formulation caused an extrusion into the intestine and peritrophic membrane. Moreover, CCD 3 showed a photodegradation of 50% (in 24 h) under white fluorescent lamps. In a small-scale field trial, CCD 3 had a residual time of 14 days and abnormal microbial growth was not observed. Finally, CCD 3 did not present any toxicity in Zebrafish, after exposition for 24 h at 100 mg/L. Overall, these results raise the possibility of reducing virus transmission through the controlled photoinactivation of Aedes aegypti larvae using a non-toxic plant-based formulated photolarvicide., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Metabolic associated fatty liver disease (MAFLD) affects a quarter of the worldwide population, but no drug therapies have yet been developed. Croton urucurana Baill. (Euphorbiaceae) is a medicinal species, that is, widely distributed in Brazil. It is used in popular medicine to treat gastrointestinal, cardiovascular, and endocrine system diseases. However, its hepatoprotective and lipid-lowering effects have not yet been scientifically investigated. Aim of the study: The present study investigated the effects of an extract of C. urucurana in a rat model of MAFLD that was associated with multiple risk factors, including hypertension, smoking, and dyslipidemia. Material and Methods: The phytochemical composition of C. urucurana was evaluated by liquid chromatography-mass spectrometry. Spontaneously hypertensive rats received a 0.5% cholesterol-enriched diet and were exposed to cigarette smoke (9 cigarettes/day for 10 weeks). During the last 5 weeks, the animals were orally treated with vehicle (negative control [C-] group), C. urucurana extract (30, 100, and 300 mg/kg), or simvastatin + enalapril (two standard reference drugs that are commonly used to treat dyslipidemia and hypertension, respectively). One group of rats that were not exposed to these risk factors was also evaluated (basal group). Blood was collected for the analysis of cholesterol, triglyceride, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. The liver and feces were collected for lipid quantification. The liver was also processed for antioxidant and histopathological analysis. Results: The main constituents of the C. urucurana extract were flavonoids, glycosides, and alkaloids. The model successfully induced MAFLD, reflected by increases in AST and ALT levels, and induced oxidative stress in the C- group. Treatment with the C. urucurana extract (300 mg/kg) and simvastatin + enalapril decreased plasma and hepatic lipid levels. In contrast to simvastatin + enalapril treatment, C. urucurana reduced AST and ALT levels. Massive lesions were observed in the liver in the C- group, which were reversed by treatment with the C. urucurana extract (300 mg/kg). Conclusion: C. urucurana extract exerted promising hepatoprotective and lipid-lowering effects in a preclinical rat model of MAFLD., 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 Auth, da Silva, Amaral, Bortoli, Manzano, de Souza, Lovato, Ribeiro-Paes, Gasparotto Junior and Lívero.)

This study evaluated the cytotoxic, genotoxic, and the modulatory effects on DNA damage of hypericin in Chinese hamster lung fibroblasts (V79 cells). The hypericin is a natural polycyclic quinone, mainly extracted from St. John's Wort ( Hypericum perforatum L.). Along with hyperforin, the hypericins are responsible for the antidepressant activity of St. John's Wort. Cytotoxicity was assessed by the XTT colorimetric assay and the nuclear division index (NDI). The genotoxic activity was studied by the micronucleus test at concentrations of 30, 60, 120, and 240 μg/mL. Mutagenic agents, methyl methanesulfonate (MMS, 44 μg/mL), doxorubicin (DXR, 0.5 μg/mL), and etoposide (VP16, 1 μg/mL) were used in combination with different concentrations of hypericin in order to evaluate the modulatory effect on DNA damage. Results showed that the hypericin was cytotoxic at concentrations above 156.2 μg/mL and genotoxic above 120 μg/mL. The hypericin significantly reduced DNA damage frequency induced by DXR, at concentrations of 30 and 60 μg/mL, and MMS at a concentration of 30 μg/mL, but was unable to reduce damage when combined with VP-16. These results demonstrate the non-photoactivated hypericin toxicological safety limits, its protective effect on DNA damage and provide a basis for future studies that may characterize better its chemopreventive mechanism.

The SARS-CoV-2 responsible for the ongoing COVID pandemic reveals particular evolutionary dynamics and an extensive polymorphism, mainly in Spike gene. Monitoring the S gene mutations is crucial for successful controlling measures and detecting variants that can evade vaccine immunity. Even after the costs reduction resulting from the pandemic, the new generation sequencing methodologies remain unavailable to a large number of scientific groups. Therefore, to support the urgent surveillance of SARS-CoV-2 S gene, this work describes a new feasible protocol for complete nucleotide sequencing of the S gene using the Sanger technique. Such a methodology could be easily adopted by any laboratory with experience in sequencing, adding to effective surveillance of SARS-CoV-2 spreading and evolution., Competing Interests: The authors have declared that no competing interests exist.

Introduction: As the Coronavirus Disease 2019 (COVID-19) pandemic unfolds around the world; answers related to the antibody response against the virus are necessary to develop treatment and prophylactic strategies. We attempted to understand part of the immune response of convalescent plasma donation candidates., Method: We carried out a cross-sectional, observational, non-intervention study, testing 102 convalescent plasma donation candidates for antibodies against the virus, relating these data to the time interval between symptom onset and sample collection, age, disease severity, and gender., Results: In our sample, the individuals who developed a greater antibody response were the ones who had a longer time interval between symptom onset and sample collection, the ones who had been hospitalized and the subjects above 35 years old. Moreover, 17 individuals did not present any reactive antibodies., Conclusion: These results are important in that they raise questions about the role of the humoral response against the virus, as some individuals do not develop antibodies to fight it. In addition, they help develop recruitment strategies for convalescent plasma donors, who should be asymptomatic for at least 21 days and are possibly more likely to have reactive antibodies after 35 days without symptoms., Competing Interests: None., (© 2021 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U.)

Croton urucurana Baill. is a native Brazilian tree, popularly known as "sangra-d'água" or "sangue-de-dragão," based on the red resinous sap of the trunk. Its use has been transmitted through generations based on popular tradition that attributes analgesic, anti-inflammatory, and cardioprotective properties to the tree. However, its cardioprotective effects have not yet been scientifically investigated. Thus, the present study investigated the pharmacological response to an ethanol-soluble fraction from the leaves of C. urucurana in Wistar rats exposed to smoking and dyslipidemia, two important cardiovascular risk factors. The extract was evaluated by high-performance liquid chromatography. Wistar rats received a 0.5% cholesterol-enriched diet and were exposed to cigarette smoke (9 cigarettes/day for 10 weeks). During the last 5 weeks, the animals were orally treated with vehicle (negative control group), C. urucurana extract (30, 100, and 300 mg/kg), or simvastatin (2.5 mg/kg) + enalapril (15 mg/kg). One group of rats that was not exposed to these risk factors was also evaluated (basal group). Electrocardiograms and systolic, diastolic, and mean blood pressure were measured. Blood was collected to measure total cholesterol, triglycerides, urea, and creatinine. The heart and kidneys were collected and processed for oxidative status and histopathological evaluation. The phytochemical analysis revealed different classes of flavonoids and condensed tannins. The model induced dyslipidemia and cardiac and renal oxidative stress and increased levels of urea and creatinine in the negative control group. Treatment with the C. urucurana extract (300 mg/kg) and simvastatin + enalapril decreased cholesterol and triglyceride levels. In contrast to simvastatin + enalapril treatment, the C. urucurana extract exerted cardiac and renal antioxidant effects. No alterations of electrocardiograms, blood pressure, or histopathology were observed between groups. These findings indicate that C. urucurana exerts lipid-lowering, renal, and cardioprotective effects against oxidative stress in a preclinical model of multiple risk factors for heart disease., Competing Interests: The authors declare that they have no conflicts of interest related to this research., (Copyright © 2021 Priscila Megda João Job Zago et al.)

In the present study, we provide a retrospective genomic epidemiology analysis of the SARS-CoV-2 pandemic in the state of Rio de Janeiro, Brazil. We gathered publicly available data from GISAID and sequenced 1927 new genomes sampled periodically from March 2021 to June 2021 from 91 out of the 92 cities of the state. Our results showed that the pandemic was characterized by three different phases driven by a successive replacement of lineages. Interestingly, we noticed that viral supercarriers accounted for the overwhelming majority of the circulating virus (>90%) among symptomatic individuals in the state. Moreover, SARS-CoV-2 genomic surveillance also revealed the emergence and spread of two new variants (P.5 and P.1.2), firstly reported in this study. Our findings provided important lessons learned from the different epidemiological aspects of the SARS-CoV-2 dynamic in Rio de Janeiro. Altogether, this might have a strong potential to shape future decisions aiming to improve public health management and understanding mechanisms underlying virus dispersion.

Aim: The purpose of this study was to evaluate the in vitro and in vivo efficiency of derivatives of 8-Hydroxyquinoline (8HQ) in controlling the fungus Ilyonectria liriodendri., Methods and Results: The in vitro tests consisted of assessing its susceptibility to the minimal inhibitory concentration (MIC) and the inhibition of mycelial growth. While the in vivo tests consisted of applying and assessing the most effective products for the protection of wounds, in both preventive + curative and curative forms. The MIC values for PH 151 (6·25 µg ml -1 ) showed better results when compared to the fungicides tebuconazole (>50 µg ml -1 ) and mancozeb (12·5 µg ml -1 for strain 176 and 25 µg ml -1 for strain 1117). PH 151 significantly inhibited mycelial growth, while mancozeb did not differ from the control. In in vivo tests, PH 151 again demonstrated excellent results in vitro, especially when applied preventively., Conclusions: The derivative of 8HQ PH 151 was effective in controlling the fungus I. liriodendri in vitro and proved to be a promising option for protecting wounds., Significance and Impact of the Study: This study points to the prospect of an effective and safe preventive antifungal product, which would enable the use of pesticides in vine culture to be reduced., (© 2021 The Society for Applied Microbiology.)

Mitotane is the only adrenolytic drug approved by the Food and Drug Administration for treating adrenocortical carcinoma (ACC). This drug has cytotoxic effects on tumour tissues; it induces cell death and antisecretory effects on adrenal cells by inhibiting the synthesis of adrenocortical steroids, which are involved in the pathogenesis of ACC. However, high doses of mitotane are usually necessary to reach the therapeutic plasma concentration, which may result in several adverse effects. This suggests that important pharmacological processes, such as first pass metabolism, tissue accumulation and extensive time for drug elimination, are associated with mitotane administration. Few studies have reported the pharmacological aspects and therapeutic effects of mitotane. Therefore, the aim of this review was to summarize the chemistry, pharmacokinetics and pharmacodynamics, and therapeutic and toxic effects of mitotane. This review also discusses new perspectives of mitotane formulation that are currently under investigation. Understanding the pharmacological profile of mitotane can improve the monitoring and efficacy of this drug in ACC treatment and can provide useful information for the development of new drugs with specific action against ACC with fewer adverse effects., (© 2020 British Pharmacological Society.)

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Resistant populations of Ae. aegypti have been a major problem in arboviruses epidemic areas, generating a strong demand for novel methods of vector control. In this regard, our group has demonstrated the use of curcumin as an efficient photoactive larvicide to eliminate Ae. aegypti larvae. This work was aimed to evaluate the Ae. aegypti (Rockefeller) development under sublethal conditions, using a curcumin/d-mannitol (DMC) formulation. The photolarvicidal efficacy under semi-field and field conditions (wild populations) was also analyzed, as well as the photobleaching and residual activity of DMC., Results: A delay in development time when larvae were exposed to sublethal concentrations of DMC was observed, followed by significant changes in sex ratio and reduction in longevity. DMC also presented a low residual activity when compared to usual larvicides, and had a substantial photolarvicidal activity against wild populations in field trials, achieving 71.3% mortality after 48 h., Conclusions: Overall, these findings are of great biological importance for the process of enabling the implementation of DMC as a new product in the control of Ae. aegypti larvae, and contributes to the improvement of new plant-based larvicides. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

In a cross-sectional study of women in a nursing team at a university hospital in southern Brazil, we studied DNA damage, salivary cortisol levels, and cognition. DNA damage was measured in blood leukocytes with the comet assay and the micronucleus test. Salivary cortisol levels were determined upon waking, 30 min later, and at bedtime. Cognition was evaluated according to the Stroop, Digit span and Word span tests. Cortisol levels on waking up were associated negatively with the number of years the employee worked at the institution and positively with the DNA damage in comet assay. Cognitive scores were lower when the cortisol levels were low at awakening and high at bedtime; and were associated positively with educational level. Cortisol status may influence overall health as well as essential work skills, such as attention., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Pain is a common and distressing symptom of many diseases and its clinical treatment generally involves analgesics and anti-inflammatory drugs. This study evaluated the toxicity of Ilex paraguariensis A. St.-Hil. (Aquifoliaceae) aqueous extract (leaves, petioles and branches) and its performance in a nociceptive response. Hepatotoxicity, psycho-stimulant test and evaluation of enzyme markers for liver damage were also tested. Chromatographic analysis by UPLC-MS demonstrated a series of isomeric monocaffeoylquinic acids, isomers of dicaffeoylquinic acid, flavonol glycosides, and saponins. Phase I and II of nociception were obtained for meloxicam, dexamethasone and aqueous Ilex paraguariensis extract. Ilex paraguariensis extract concentration was negatively correlated ( R = -0.887) with alanine aminotransferase ( p < 0.05) in acetaminophen-induced hepatotoxicity test, indicating hepatoprotective activity of this extract. Ilex paraguariensis extract also presented analgesic properties equivalent to drugs that already have proven efficacy. Notably, the administration of multiple doses of Ilex paraguariensis extract was considered safe from the therapeutic point of view., (© 2021 Luciana C. Nowacki et al., published by Sciendo.)

Barks of trees of the genus Handroanthus are known for their antitumor activity, which is attributed to naphthoquinones. Another class of molecules that has shown antitumor activity are the polysaccharides, however those from Handroanthus barks have never been studied. Accordingly, the aim of this study was to extract polysaccharides from H. heptaphyllus and H. albus barks, to characterize them structurally and to evaluate their cytotoxic effects on the human colon and human breast cancer cell lines, Caco-2 and MCF-7, respectively. The polysaccharides were extracted with boiling water and fractionated by freeze-thawing process. The soluble polysaccharide fractions HHBSF and HABSF were characterized by monosaccharide composition, methylation and NMR analyses, and their effects on proliferation of Caco-2 and MCF-7 cells were evaluated using MTT cell viability assay. HHBSF and HABSF were mainly constituted of galactoglucomannan, type II arabinogalactan (AGII) and type I rhamnogalacturonan (RGI), however, only HABSF significantly inhibited the growth of MCF-7 (CC50 = 327 μg/mL) and Caco-2 (CC50 = 2258 μg/mL) cells. Differences in the fine structure and proportion of their polysaccharides, and maybe in the composition of associated phenolic compounds could explain the different effects of HHBSF and HABSF., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The management of germplasm banks is complex, especially when many accessions are involved. Microsatellite markers are an efficient tool for assessing the genetic diversity of germplasm collections, optimizing their use in breeding programs. This study genetically characterizes a large collection of 410 grapevine accessions maintained at the Agronomic Institute of Campinas (IAC) (Brazil). The accessions were genotyped with 17 highly polymorphic microsatellite markers. Genetic data were analyzed to determine the genetic structure of the germplasm, quantify its allelic diversity, suggest the composition of a core collection, and discover cases of synonymy, duplication, and misnaming. A total of 304 alleles were obtained, and 334 unique genotypes were identified. The molecular profiles of 145 accessions were confirmed according to the literature and databases, and the molecular profiles of more than 100 genotypes were reported for the first time. The analysis of the genetic structure revealed different levels of stratification. The primary division was between accessions related to Vitis vinifera and V. labrusca, followed by their separation from wild grapevine. A core collection of 120 genotypes captured 100% of all detected alleles. The accessions selected for the core collection may be used in future phenotyping efforts, in genome association studies, and for conservation purposes. Genetic divergence among accessions has practical applications in grape breeding programs, as the choice of relatively divergent parents will maximize the frequency of progeny with superior characteristics. Together, our results can enhance the management of grapevine germplasm and guide the efficient exploitation of genetic diversity to facilitate the development of new grape cultivars for fresh fruits, wine, and rootstock., Competing Interests: The authors have declared that no competing interests exist.

Handroanthus albus, commonly known as yellow ipê, is a native and widely distributed tree in Brazil. An aqueous soluble polysaccharide fraction (HASP) was obtained from its leaves, and monosaccharide composition, glycosidic linkage analysis by methylation and NMR spectroscopy indicated that HASP is mainly composed of a type II arabinogalactan, and suggested that other polysaccharides could also be present in a smaller proportion. HASP was able to promote antinociception in formalin-induced (second phase) and on glutamate-induced nociception tests, besides reducing the number of abdominal contortions induced by acetic acid in mice. Moreover, HASP reduced acetic acid-induced leukocyte infiltration in the peritoneal cavity and showed anti-edematogenic activity, decreasing mechanical allodynia and myeloperoxidase activity in the carrageenan-induced paw edema model. These results showed that the polysaccharide fraction HASP from H. albus leaves has interesting antinociceptive and anti-inflammatory activities., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Combating the Aedes aegypti vector is still the key to control the transmission of many arboviruses, such as Dengue, Zika, and Chikungunya. As few products are efficient for Aedes aegypti control, the search for new strategies have become pivotal., t Substances with photodynamic activity, such as curcumin and their formulations, are strongly encouraged, due to their multi-target mechanism of action. In this study, we evaluated the photolarvicidal and ovicidal activity of curcumin in the presence of sucrose (named SC) and d-mannitol (named DMC). To support the understanding of the larvicidal action of these formulations, Raman micro-spectroscopy was employed. We also studied the morphological changes in Danio rerio (Zebrafish) gills, a non-target organism, and demonstrate that this is an environmentally friendly approach. Both SC and DMC presented a high photo-larvicidal potential. DMC showed the highest larval mortality, with LC 50-24h values between 0.01 and 0.02 mg.L -1 . DMC also significantly decreased egg hatchability, reaching a hatching rate of 10 % at 100 mg.L -1 . The analysis of molecular mechanisms via Raman micro-spectroscopy showed that DMC is highly permeable to the peritrophic membrane of the larva, causing irreversible damage to the simple columnar epithelium of the digestive tube. Histological changes found in the D. rerio gills were of minimal or moderate pathological importance, indicating an adaptive trait rather than detrimental characteristics. These findings indicate that curcumin in sugar formulations is highly efficient, especially DMC, proving it to be a promising and safe alternative to control Aedes mosquitoes. Moreover, Raman micro-spectroscopy demonstrated high potential as an analytical technique to understand the mechanism of action of larvicides., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aedes aegypti is the vector of important diseases like dengue, zika, chikungunya, and yellow fever. Vector control is pivotal in combating the spread of these mosquito-borne illnesses. Photoactivable larvicide curcumin obtained from Curcuma longa Linnaeus has shown high potential for Ae. aegypti larvae control. However, the toxicity of this photosensitizer (PS) might jeopardize non-target aquatic organisms. The aim of this study was to evaluate the toxicity of this PS to Daphnia magna and Danio rerio, besides assessing its mode of action through larvae biochemical and histological studies. Three PS formulations were tested: PS in ethanol+DMSO, PS in sucrose, and PS in D-mannitol. The LC 50 of PS in ethanol+DMSO to D. rerio was 5.9 mg L -1 , while in D. magna the solvents were extremely toxic, and LC 50 was not estimated. The PS formulations in sugars were not toxic to neither of the organisms. Reactive oxygen species (ROS) were generated in D. magna exposed to 50 mg L -1 of PS in D-mannitol, and D. rerio did not elicit this kind of response. D. magna feeding rates were not affected by the PS in D-mannitol. Concerning Ae. aegypti larvae, there were changes in reduced glutathione and protein levels, while catalase activity remained stable after exposure to PS in D-mannitol and sunlight. Histological changes were observed in larvae exposed to PS in sucrose and D-mannitol, most of them irreversible and deleterious. Our results show the feasibility of this photolarvicide use in Ae. aegypti larvae control and its safety to non-target organisms. These data are crucial to this original vector control approach implementation in public health policies.

Ethnopharmacological Relevance: Euphorbia tirucalli L. is an African plant that grows well in Brazil. Individuals diagnosed with cancer frequently consume latex from E. tirucalli, dissolved in drinking water. In vitro studies confirm the antitumor potential of E. tirucalli latex, but in vivo evaluations are scarce., Aim of the Study: To evaluate the effect of intake of an aqueous solution of E. tirucalli latex on tumor growth, cachexia, and immune response in Walker 256 tumor-bearing rats., Materials and Methods: Latex from E. tirucalli was collected and analyzed by LC-MS. Sixty male Wistar rats (age, 90 days) were randomly divided into four groups: C, control group (without tumor); W, Walker 256 tumor-bearing group; SW1, W animals but treated with 25 μL latex/mL water; and SW2, W animals but treated with 50 μL latex/mL water. Animals received 1 mL of latex solution once a day by gavage. After 15 d, animals were euthanized, tumor mass was determined, and glucose and triacylglycerol serum levels were measured by using commercial kits. Change in the body weight during tumor development was calculated, and proliferation capacity of tumor cells was assessed by the Alamar Blue assay. Phagocytosis and superoxide anion production by peritoneal macrophages and circulating neutrophils were analyzed by enzymatic and colorimetric assays. Data are analyzed by one-way ANOVA followed by Tukey's post-hoc test, with the significance level set at 5%., Results: The analysis of the latex revealed the presence of triterpenes. The ingestion of the latex aqueous solution promoted 40% and 60% reduction of the tumor mass in SW1 and SW2 groups, respectively (p < 0.05). The proliferative capacity of tumor cells from SW2 group was 76% lower than that of cells from W group (p < 0.0001). Animals treated with latex gained, on average, 20 g (SW1) and 8 g (SW2) weight. Glucose and triacylglycerol serum levels in SW1 and SW2 animals were similar to those in C group rats. Peritoneal macrophages and blood neutrophils from SW1 and SW2 animals produced 30-40% less superoxide anions than those from W group animals (p < 0.05), but neutrophils from SW2 group showed an increased phagocytic capacity (20%, vs. W group)., Conclusions: E. tirucalli latex, administered orally for 15 d, efficiently reduced tumor growth and cachexia in Walker 256 tumor-bearing rats. Decreased tumor cell proliferative capacity was one of the mechanisms involved in this effect. Further, the data suggest immunomodulatory properties of E. tirucalli latex. The results agree with folk data on the antitumor effect of latex ingestion, indicating that it may be useful as an adjunct in the treatment of cancer patients. For this, further in vivo studies in animal and human models need to be conducted., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Acmella oleracea ("jambu") is an Amazonian plant rich in alkylamides. Its flowers are widely used in folk medicine to treat toothache due to tingling, numbness, and local anaesthesia caused in the mouth. Our group previously demonstrated that the intraplantar (i.pl.) injection of an alkylamide-rich hexane fraction (HF) obtained from jambu flowers and a synthetic isobutylalkyl amide (IBA) displayed antinociceptive and anesthetic effects in acute pain models. Thus, here we evaluated the effects of HF and IBA on carrageenan-induced acute inflammation. Mice were pretreated with HF or IBA (0.01, 0.1, and 1 µg/20 µL, i.pl.) 15 min before carrageenan injection (300 µg/20 µL, i.pl.). Mechanical allodynia and paw oedema were evaluated previously (basal) and at 0.5 until 6 h following carrageenan. Both HF and IBA at 0.1 µg promoted effective and long-lasting antiallodynic and anti-oedematogenic activities until 3 and 5 h, respectively, in comparison to the different doses evaluated. At the inflammatory peak, the plantar surfaces were excised for measurement of inflammatory and oxidative stress parameters. HF and IBA (0.1 µg) reduced the myeloperoxidase activity, TNF-α and IL-1β levels, prevented the production of lipid hydroperoxides, and the decrease of antioxidant agents, namely superoxide dismutase and catalase activities, and glutathione contents. Furthermore, only HF maintained IL-10 levels and decreased PGE 2 synthesis. On the basis of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, HF and IBA are devoid of antioxidant activity in vitro. Collectively, our results demonstrated the promising anti-inflammatory effect of local pretreatment with alkylamides, supporting the potential of these molecules to treat acute inflammatory pain conditions.

Background: Given the aging of the population, nephrologists are ever more frequently assisting nonagenarians with acute kidney injury (AKI). The management of these patients presents unique characteristics, including bioethical dilemmas, such as the utilization of renal replacement therapy (RRT) at this extreme age., Methods: We conducted a retrospective cohort study at a tertiary hospital. Over a 10-year period, 832 nonagenarians were hospitalized for two or more days. A random sample of 461 patients was obtained; 25 subjects were excluded due to lack of essential data. AKI was defined and staged according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria., Results: We analyzed data from 436 patients, mean age 93.5 ± 3.3 years, 74.3% female; 76.4% required intensive care unit (ICU). The incidence of AKI was 45%. Length of hospital stay, ICU admission, vasopressors, and mechanical ventilation (MV) were independent predictors of AKI. Overall in-hospital mortality was 43.1%. Mortality was higher in the AKI compared to the no AKI group (66.8% vs. 23.8%, p < 0.001). Only 13 patients underwent RRT; all were critically ill, requiring vasopressors and 76.9% in MV. Mortality for this RRT group was 100% but not significantly higher than that observed in 26 non-RRT controls (96.1%, p = 1.0) obtained by proportional random sampling, matched by variables related to illness severity. In multivariable analysis, age, Charlson's score, vasopressors, MV, and AKI - but not RRT - were independent predictors of mortality., Conclusions: AKI is common in hospitalized nonagenarians and carries a grave prognosis, especially in those who are critically iil. The use of RRT was not able to change the fatal prognosis of this subgroup of patients. Our data may help guide informed decisions about the utility of RRT in this scenario.

The aim of the study was to investigate the association between blood and tissue levels of selenium and thyroid cancer through a systematic review. We searched for observational studies written in English, Spanish, and Portuguese indexed in PubMed, LILACS, and Scielo without date restriction, that evaluated the association between selenium levels in whole-blood, serum, or plasma and/or thyroid tissue and thyroid cancer, both in individuals with cancer of thyroid as in healthy individuals. Then data were extracted and analyzed. Of the 570 articles identified, five cross-sectional studies were included in the review. In one study, lower concentrations of selenium were found in whole-blood (0.543 μg/ml) and in the thyroid (0.88 μg/g) of thyroid cancer patients compared to controls. Another study showed a decrease in serum selenium concentrations in patients with follicular carcinoma and papillary types (0.077 ± 0.021 μg/ml and 0.080 ± 0.020 μg/ml, respectively). On the other hand, other studies showed no difference in plasma selenium content or glutathione peroxidase activity among patients and healthy volunteers. The available evidence on this issue is inconclusive. Additional studies are needed to elucidate the association between serum and/or tissue levels of selenium and the development of thyroid cancer.

A polysaccharide fraction from Handroanthus heptaphyllus leaves was obtained with a simple and quick purification method. Methylation analysis and NMR spectroscopy indicated the presence of a complex polysaccharide fraction mainly constituted by a type II arabinogalactan. This is the first report in literature on structural elucidation of polysaccharides of species from genus Handroanthus. Oral and intraperitoneal administration of the polysaccharide fraction from Handroanthus heptaphyllus (HHSF) protected the gastric mucosa in an acute model of gastric lesion induced by ethanol, preserving gastric mucus. Furthermore, in the indomethacin model, HHSF reduced wounded area and inhibited mucus and GSH depletion. HHSF also accelerated gastric ulcer healing, accompanied by the maintenance of GSH levels. In addition, in an oxidative stress model with human epithelial cell line (Caco-2), HHSF was able to preserve GSH levels and was not toxic to cells. Collectively, these results showed that HHSF has an interesting antiulcerogenic activity and could constitute an interesting option for the treatment of gastric ulcer., (Copyright © 2019 Elsevier Ltd. All rights reserved.)