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Quinones are chemical compounds produced from the oxidation of phenols. Among the quinones, naphthoquinones stand out as potential antitumor agents. Bladder tumour is the tenth most diagnosed in the world. Based on this, using a urothelial carcinoma cell line (T24), two naphthoquinones had their cytotoxicity tested by the MTT colorimetric method and were submitted to assays of clonogenic survival, morphology, cell cycle, cell migration and species reactive oxygen. The results showed 8-methoxy-α-lapachone and lausone presented selectivity indexes (19.5 and 28.0, respectively) for T24 cells. Moreover, the two naphthoquinones reduced the cell viability, interfered with the process of cell migration, changed the cell cycle kinectics and induced the production of species reactive oxygen (ROS). Additionaly, 8-methoxy-α-lapachone altered the morphology of the cells. In conclusion, the studied naphthoquinones showed potential antiproliferative effects in bladder cancer cells, interfering in cellular processes, possibly through oxidative stress. more...

Background: Methotrexate (MTX), a folic acid antagonist used in chemotherapy, faces limitations due to cancer cell resistance, high toxicity, and low bioavailability. Objective: This study developed nanoparticles (NPs) of chitosan (QS) and hydroxypropylmethylcellulose phthalate (HPMCP) to encapsulate MTX for potential effect investigation on glioblastoma cell targeting and P-gp efflux inhibition. Method: NPs were produced by the polyelectrolyte complexation method and were characterized by DLS, PDI, DSC, FTIR, PXRD, MEV, drug release profile, and an in vitro mucoadhesion test. Cell viability, flow cytometry, and LSCM using U251MG (glioblastoma) and CCD 1059Sk (fibroblasts) cells were used to evaluate glioblastoma and the P-gp efflux effect. Results: NPPM29 (QS3:1) showed 91.72% encapsulation efficiency, a mean diameter of 452.6 nm, and a zeta potential of +22.5 mV. DSC, FTIR, and PXRD confirmed the QS-HPMCP supramolecular interaction. Liquid falling mucoadhesion tests demonstrated strong retention of NPPM29 (84%) compared to free MTX (10.5%). In vitro release studies indicated controlled drug release at pH 7.4. Cytotoxicity assays in U251MG revealed enhanced efficacy of NPPM29 (IC 50 = 68.79 µg/mL) compared to free MTX ( IC 50 = 80.54 µg/mL), with minimal impact on fibroblasts, confirming tumor specificity. Flow cytometry and LSCM confirmed improved cellular internalization and P-gp inhibition. Conclusions: These findings highlight the potential of MTX-QS-HPMCP-NPs for glioblastoma therapy. more...

Digitaria insularis poses a significant challenge in weed control due to its perennial habit, dense clumping growth, and the widespread presence of herbicide-resistant biotypes. Our research investigates whether single or multiple herbicide resistance biotypes of D. insularis experience fitness costs, specifically affecting their germination. To determine the resistance factor, a dose-response curve was employed using glyphosate and haloxyfop-P-methyl herbicides separately in a completely randomized design (CRD) with four replicates per dose (nine doses total). Shoot dry mass was measured at 100 days after herbicide application (DAA), with control assessments performed at 14, 28, and 42 DAA. Subsequently, a separate CRD experiment examined the germination rate as a function of temperature and photoperiod for each biotype. This factorial scheme tested six temperatures across three biotypes (susceptible and two resistant types) under three light exposure periods (0, 8, and 12 hours). Germination percentage and the germination speed index (GSI) were calculated for 14 days, with counts of healthy seedlings recorded daily. Statistical analysis confirmed the resistance/susceptibility of the biotypes based on the dose-response curve. For the susceptible and simple resistance biotypes, the most favorable temperatures for germination were 20, 30 and 40 °C, at which the highest germination percentages and a higher germination speed index were observed. On the other hand, for the biotype with multiple resistance, the temperatures of 25, 30 and 35 °C were more favorable, promoting superior results in both parameters studied. more...

This report describes the occurrence of the rabies virus in two species of wild animals in the urban area of Montes Claros (MOC), Minas Gerais State, Brazil, in May 2023. The virus has been detected in frugivorous chiropterans (Artibeus sp) and marmosets (Callithrix penicillata). This is the first notified case of the rabies virus in the species C. penicillata in the urban area of MOC. Our findings show that the rabies virus is circulating in the urban area of MOC; therefore, permanent preventive measures must be adopted to avoid infection of other animals and humans. more...

The aim of this study was to evaluate the effects of pregnant ewe nutrition on the performance of offspring in terms of meat, wool production, and reproduction. Foetal programming in sheep has focused on several aspects related to foetal growth, postnatal production, behaviour, and immunological performance. Currently, significant efforts are being made to understand the endocrine, metabolic, and epigenetic mechanisms involved in offspring development. Current studies have not only evaluated the foetal period, despite the pre-conception parental nutrition has demonstrated an effect on the foetal, embryonic, and pre-implantation periods and can generate permanent effects in the foetal and postnatal phases. The performance of offspring is the result of interactions between the genome, epigenome, and environmental interventions during conception. Several factors influence the expression of phenotypic characteristics in progenies; however, this study focused on presenting data on the effect of pregnant ewe nutrition alone on foetal growth and the productive aspects of their offspring., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced in this article, entitled “Foetal programming in sheep: Reproductive and productive implications”., (Copyright © 2024 Elsevier B.V. All rights reserved.) more...

Water is a scarce, strategic resource and the most important input for economic development, especially in agricultural countries such as Brazil. Cocoa production is directly related to water availability, and, as climate changes, selecting drought-tolerant genotypes is vital to keep cacao crops sustainable. Here, we evaluated cacao genotypes under irrigated and water-stressed conditions and selected drought-tolerant ones based on nutritional and physiological traits. Thirty-nine genotypes were monitored for three years for agronomic traits and higher fruit yield. After this evaluation, the 18 most promising genotypes were evaluated in a randomized block design, under a 2 (with and without irrigation)  ×  18 (genotypes) factorial arrangement, with three replicates and five plants per plot. We evaluated seven physiological and 11 nutritional traits, selecting genotypes based on the Genotype-by-Trait Biplot approach. Significant effects (p < 0.05) were observed for the nutritional traits N, P, Mg, S, Zn, Cu, Mn and for the physiological traits CO 2 assimilation rate (A), stomatal conductance (gs), transpiration (E), intercellular and atmospheric CO 2 concentrations (Ci/Ca), intrinsic water use efficiency (A/gs), instantaneous water use efficiency (A/E), and instantaneous carboxylation efficiency (A/Ci), as determined by analysis of variance. The genotype  ×  irrigation treatment interaction was significant (p < 0.05) for the traits A, gs, and E. Genotypes CP 41, CP 43, and CCN 51 exhibited superior performance for both nutritional and physiological traits (A, gs, and E). In the irrigated environment, CP 41 showed superiority in traits such as P, A/E, A/gs, Mn, S, and Zn. Conversely, under non-irrigated conditions, CP 43 exhibited better performance in nutritional properties, specifically Mn, Mg, and Zn. Notably, in both irrigated and non-irrigated environments, CCN 51 excelled in key physiological traits, including A/Ci, A/E, and A/gs. This robust performance across diverse conditions suggests that these three genotypes possess physiological mechanisms to endure water-stressed conditions. Our research can generate valuable insights into these genotypes informing suitable choices for cocoa cultivation, especially in the context of global climate change., (© 2024. The Author(s).) more...

Key Message: We propose an "enviromics" prediction model for recommending cultivars based on thematic maps aimed at decision-makers. Parsimonious methods that capture genotype-by-environment interaction (GEI) in multi-environment trials (MET) are important in breeding programs. Understanding the causes and factors of GEI allows the utilization of genotype adaptations in the target population of environments through environmental features and factor-analytic (FA) models. Here, we present a novel predictive breeding approach called GIS-FA, which integrates geographic information systems (GIS) techniques, FA models, partial least squares (PLS) regression, and enviromics to predict phenotypic performance in untested environments. The GIS-FA approach enables: (i) the prediction of the phenotypic performance of tested genotypes in untested environments, (ii) the selection of the best-ranking genotypes based on their overall performance and stability using the FA selection tools, and (iii) the creation of thematic maps showing overall or pairwise performance and stability for decision-making. We exemplify the usage of the GIS-FA approach using two datasets of rice [Oryza sativa (L.)] and soybean [Glycine max (L.) Merr.] in MET spread over tropical areas. In summary, our novel predictive method allows the identification of new breeding scenarios by pinpointing groups of environments where genotypes demonstrate superior predicted performance. It also facilitates and optimizes cultivar recommendations by utilizing thematic maps., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) more...

Background: Longitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19., Methods: We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both., Results: Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44-18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53)., Conclusions: In our global cohort, death was the outcome in >10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2023.) more...

Objective: The objective of this study was to estimate the seroprevalence of severe acute respiratory syndrome coronavirus 2 antibodies in patients with tuberculosis., Methods: This cross-sectional study was conducted at an outpatient tuberculosis clinic in Alvorada, RS, Brazil, with data collection between October and December 2020. Outpatients aged>18 years with active pulmonary tuberculosis, no prior history of coronavirus disease 2019, and no suspected coronavirus disease 2019 were included in the study. Whole blood samples were collected to perform the severe acute respiratory syndrome coronavirus 2 antibodies test., Results: During the study period, 52 patients met the inclusion and were included in the analysis. Severe acute respiratory syndrome coronavirus 2 antibodies were positive in 16 (30.8%) patients. Male sex was more frequent among patients with negative severe acute respiratory syndrome coronavirus 2 antibodies than in patients with positive severe acute respiratory syndrome coronavirus 2 antibodies (86.1 vs. 56.3%, p=0.031). Contact with coronavirus disease 2019 case was more common in patients with positive severe acute respiratory syndrome coronavirus 2 antibodies compared with patients with negative severe acute respiratory syndrome coronavirus 2 antibodies (87.5 vs. 8.3%, p<0.0001). In a multivariate analysis, in a model including the variables such as male sex and contact with coronavirus disease 2019 case, only contact with coronavirus disease 2019 was independently associated with positive severe acute respiratory syndrome coronavirus 2 antibodies (OR 77.0, 95%CI 11.5-512.4, p<0.0001)., Conclusion: This study revealed a seroprevalence of 30.8% severe acute respiratory syndrome coronavirus 2 among patients with tuberculosis. more...

Naphthoquinones are natural plants products or synthesized compounds. They have α, β-cyclic aromatic dienones structure with a naphthalene skeleton. Little is known about naphthoquinone and nothing about naphtho [2,3-b] thiophen-4,9-quinone effects on bladder cancer. In this study, a naphthoquinone containing a hetero sulfur atom was synthesized using classical synthetic method. The molecular structure was elucidated by NMR techniques and the antitumor effects were evaluated on bladder tumor cell lines with different TP53 status using tripan blue and MTT cytotoxic method, quantification of reactive oxygen species (ROS), wound healing, cell morphology and cell cycle progression assays. The results showed selective cytotoxicity, colonies reduction, morphological change, inhibition of the cell migration process, induction of ROS production and cell cycle arrest. Naphtho [2,3- b ] thiophen-4,9-quinone presents antiproliferative activity regardless TP53 status and may be a promising agent in the treatment of bladder cancer, as they have an oxidizing effect and interfere with cell cycle. more...

Thermography has grown in use in recent years. It is a valuable tool for measuring animal heat tolerance under heat stress conditions since it is a non-invasive, safe and practical methodology. Physiological variables such as respiration rate and eye temperature, and environmental variables such as air temperature and wet bulb temperature were analysed in animals from nine cattle breeds (Angus, Braford, Brangus, Canchim, Charolais, Hereford, Nelore, Simmental and Santa Gertrudis) and one bubaline (Mediterranean) at Rio Grande do Sul, Brazil. Positive correlations were observed between air temperature and respiration rate and eye temperature. Furthermore, the breed strongly influenced the eye temperature and respiration rate of the animals. Eye temperature showed strong correlation with air temperature and wet bulb temperature. Simmental and Nelore animals presented higher eye temperature values. Simmental presented alteration in respiratory rate before the other breeds and Nelore was the last breed to present this alteration. The inflection points in the broken line analysis indicated the environmental temperature limits at which breeds begin to change their respiration to compensate for environmental variation. The use of thermography has proven to be a technique with possible application to evaluate the temperature of animals. Logistic regression analysis allows us to observe how each breed behaves with the temperature change. Using respiration rates and eye temperatures it was possible to identify physiological limits for comfort in different breeds of bovine. In the future it would be interesting to conduct additional studies using other physiological variables and also other indices of climatic conditions., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.) more...

This study aimed to investigate the effect of age at weaning of calves on non-esterified fatty acids (NEFA) and reproductive parameters of beef cows. Animals (n = 65) were randomly assigned to three treatments after calving: hyper-early weaning (W30) at 32 ± 0.89 days, early weaning (W75) at 77 ± 0.95 days, and conventional weaning (W180) at 183 ± 0.82 days. Body weight (BW) and body condition score (BCS) were evaluated at parturition (AP) and at 30, 45, 64, 81, 100 and 115 days postpartum (dPP). Blood samples were collected to analyze NEFA levels and progesterone (P4) at 30, 45, 64 and 81 dPP. Higher BW and BCS were observed from 64 to 115 dPP in W30 cows than W180 ones (p < 0.05). Cows subjected to W30 condition had higher levels of NEFA at 30 dPP compared to 64 and 81 dPP (p < 0.05). We also observed that cows from W180 group showed decreased levels of NEFA at 30 dPP compared to 45 (p < 0.01) and 64 dPP (p < 0.05). The highest P4 level was observed at 64 dPP in W30 cows compared to W75 and W180 (p < 0.05). We also observed higher CR of W30 (86%) compared to W180 (47%) at 45 dPP (p < 0.05). The overall pregnancy rate (PR) was higher for W30 (95.5%) than W180 (73.9%). In addition, higher BW at calving and P4 levels at 30 dPP were positively correlated with the possibility of pregnancy (p < 0.05). Improvement in BW and BCS were observed in cows subjected to hyper-early weaning management. However, levels of NEFA decreased as the postpartum period progressed. We concluded that cows who weaned calves hyper-early have greater chances of increasing cyclicity and PRs., (© 2022 Wiley-VCH GmbH.) more...

This experiment was conducted to determine the effect of earlier weaning in addition to biocholine supplementation on age at puberty of Brangus heifers. Brangus calves were randomized and divided into three weaning ages groups, at 30 (Hyper-early weaning; HW), 75 (Early weaning; EW) and 180 days (Conventional weaning; CW). Then, calves were supplemented using the additive Biocholine (BIO) or not (CON). Animals were subjected to puberty induction and the presence of estrus was observed for 7 days. In addition, transrectal ultrasonography was performed to assess the ovarian activity and the presence of corpus luteum to determine heifer puberty. We also evaluated the body weight (BW; Kg), hip height (HH; cm), thoracic perimeter (TP; cm) and BW:HH ratio during the experimental period. BIO group showed higher ADG (>226 g/day) when the animals were exposed to ryegrass pasture compared to CON (P < 0.05). We observed an interaction between weaning x biocholine and CW-BIO heifers showed greater HH more compared to CW-CON (P < 0.05). Overall, animals that have reached puberty at day 8 after puberty induction showed 331.0 ± 5.04 kg BW, 122.0 ± 0.56 cm HH and 165.4 ± 0.75 cm TP and 2.7 ± 0.03 BW:HH. At the time of ovulation detection, the heifers from the HW group had 32.1 kg BW, 3.93 cm HH and 0.18 cm BW:HH greater compared to CW (P < 0.05). The BIO supplementation together with ryegrass pasture, led to an increase in ADG weight throughout the evaluated period. We concluded that HW heifers showed an adequate body development throughout the experimental period until puberty appearance at the same age as others weaned groups., (Copyright © 2022 Elsevier Ltd. All rights reserved.) more...

Evidence of sylvatic yellow fever was first reported in Atlantic Forest areas in Espírito Santo, Brazil, during a yellow fever virus (YFV) outbreak in 1931. An entomological survey was conducted in six forest sites during and after an outbreak reported ~80 years after the last case in the area. Among 10,658 mosquitoes of 78 species, Haemagogus leucocelaenus, and Hg. janthinomys / capricornii were considered the main vectors as they had a relatively high abundance, co-occurred in essentially all areas, and showed high YFV infection rates. Sabethes chloropterus , Sa. soperi , Sa. identicus , Aedes aureolineatus , and Shannoniana fluviatilis may have a secondary role in transmission. This is the first report of Sa. identicus , Ae. aureolineatus , and Sh. fluviatilis infected with YFV. Our study emphasizes the importance of entomological monitoring and maintenance of high vaccination coverage in receptive areas to YFV transmission. more...

The present systematic review and meta-analysis aim to summarize the effects of maternal undernutrition or overnutrition during pregnancy on the absolute weight and relative weight of the organs (liver, kidneys, heart, spleen, and lung) and glands (adrenal, pancreas, and thyroid) measured during gestation, birth and the postnatal period in lambs. After completing the search, selection, and data extraction steps, the measure of effect was generated by the individual comparison of each variable response compared with the average of the control and treated group (undernutrition or overnutrition) using the DerSimonian and Laird method for random effects. The liver was the organ most affected by maternal undernutrition, as the absolute weight of the liver was reduced during pregnancy, birth, and the postnatal period. The extent of this effect is related to the duration of the intervention. Reductions in the absolute fetal weight of the lungs and spleen have also been observed. No change in organs weight were observed when the results were expressed as relative weight. For overnutrition, the fetal weight of the liver was reduced to both absolute and relative values. In contrast, the relative weight of the kidneys has been increased. For the glands analyzed, no changes in weight were observed in either scenario (absolute or relative weight). Thus, the organs are more likely to suffer weight changes, especially during pregnancy, as a result of maternal nutrition. However, this change in organ weight seems to be closely related to the reduction in body weight of the progeny as a whole., Competing Interests: Declaration of Competing Interest The authors declare there are no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.) more...

Biomass valorization is essential, particularly in emerging countries. Here, hydrochar from arabica coffee straw was functionalized with a triazole group (HD-TRz) for use as a support of palladium nanoparticles (PdNPs-HD-TRz) applied in the Ullmann coupling reaction for the first time. It provided remarkably excellent selectivities, conversions at a temperature as low as 45 °C and catalyst recyclability, surpassing previous literature performances. Hydrochar was obtained by one-pot reaction via hydrothermal synthesis, using NaOH solution as activating agent and functionalized with a 1,3-triazole group by CuAAC "click" reaction. The PdNPs were prepared via reduction of hydrochar-bound Pd(II) using NaBH 4 . Hydrochar functionalization was monitored by infrared spectroscopy, and X-ray diffraction (XRD) allowed to observe carbon and palladium planes in hydrochar and PdNPs HD-TRz structures. The PdNPs presented a spherical shape with 2.1 ± 0.1 nm size, homogeneously distributed in the carbon coverslips. The HD-TRz-supported PdNPs were used as a catalyst in the Ullmann reaction of iodobenzene, using ethanol as solvent with 100% of conversion and 91% selectivity at 45 °C. The material was reused, presenting 100% of conversion and selectivities of 92, 84 and 73% for the 1st, 2nd and 3rd cycle, respectively. The scope of the reaction was expanded to other molecules showing the potential of this and other triazole-hydrochar-supported nanocatalysts., 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 © 2022 Elsevier Ltd. All rights reserved.) more...

This study evaluated the effect of climate change on andrological parameters of beef bulls raised under tropical, subtropical, and temperate conditions. Bull ejaculates were collected to evaluate seminal quality parameters, sperm membrane integrity, and redox status (SOD; GPx; GSH; GRx; CARB; DCF; and SOD/GPx ratio). Bulls located in the temperate region showed a higher sperm motility rate and percentage of viable sperm (P < 0.05). When evaluating regions independently, we observed a lower GPx activity from animals in the tropical region (P < 0.05). In contrast, we found that SOD and GRx activities, GSH content, and CARB oxidative levels were higher in the tropical region, while oxidation values of DCF were lower (P < 0.05). Braford bulls showed higher CARB and DCF levels (1.23 ± 0.61 nmol/mg and 1453.60 ± 828.63 nmol/mg, respectively) compared to Hereford bulls (1.00 ± 0.43 nmol/mg and 1138.70 ± 423.24 nmol/mg, respectively) in the temperate region. However, Nellore bulls showed higher DCF levels (650.50 ± 401.53 nmol/mg) than Braford bulls (409.40 ± 286.97 nmol/mg). In addition, the SOD/GPx ratio was lower in Braford (12.44 ± 7.64 U/mg) compared to Nellore bulls in tropical conditions (87.25 ± 2.83 U/mg). A positive correlation was found in temperate conditions between DCF levels, SOD, and GRx activities (0.51, 0.58; P < 0.01, respectively), as well as in subtropical conditions between DCF levels and GRx activity (0.53; P < 0.01). A negative correlation between the temperature-humidity index and CARB content was found in subtropical and tropical regions (-0.44; P < 0.01). We concluded that Braford breeds showed lower seminal motility, DCF contents and SOD/GPx ratios compared to Nellore bulls in tropical climate conditions. Finally, in temperate environmental conditions, Braford bulls also showed lower seminal motility but higher levels of CARB and DCF contents compared to Hereford bulls. Therefore, the existence of climatic differences between the temperate and tropical regions evaluated affected Braford bulls' seminal motility and seminal redox homeostasis., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest that could be perceived as reducing the impartiality of the research reported., (Copyright © 2022 Elsevier Ltd. All rights reserved.) more...

Objective: Psoriasis is a chronic inflammatory skin disorder. Oral or subcutaneous methotrexate (MTX) is a first-line antipsoriatic treatment, whose adverse effects can be observed even at low doses. To minimize systemic side effects, antipsoriatic drugs should be administered topically, since they could permeate the stratum corneum. As liquid crystals with lamellar phase (LP) can be helpful in promoting skin permeation, this work evaluated two MTX-loaded LPs (C1CH and C1CHCE), based on stearic acid, cholesterol and ceramides, like topical treatments for mice with imiquimod-induced psoriasis., Methods: C1CH and C1CHCE were topically administered to mice with imiquimod-induced psoriasis. Dexamethasone cream was used as positive treatment control. Skin histology and inflammation biomarkers were assessed., Key Findings: C1CH and C1CHCE exhibited marked immunomodulatory effects and induced extensive microstructural skin remodelling on the epidermis and dermis. These formulations increased keratinization score, epidermis thickness, inflammatory infiltrate, hair follicle hypertrophy and vascular congestion in the dermis. C1CH and C1CHCE also attenuated IL-10 upregulation and upregulated IL-1, IFN-γ, TNF-α and prostaglandin E2 levels, as well as myeloperoxidase, N-acetyl-β-d-glucosaminidase and cyclooxygenase 2 activity compared with untreated psoriatic animals., Conclusion: Although liquid crystals have been reported as good options for carrying topical drugs, they need to be carefully assessed on a case-by-case basis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. 
For permissions, please e-mail: journals.permissions@oup.com.) more...

Mosquito species of the subgenus Decamyia Dyar, 1919 of genus Wyeomyia Theobald, 1901 are known to have immature stages mostly associated with Heliconia plants. Currently, the subgenus includes five species, some of which are poorly characterized. Here, we redescribe and illustrate the larval, pupal and adult life stages of Wy. felicia (Dyar Nez Tovar, 1927). In addition, Wyeomyia monticola, a new species of Decamyia from Trinidad, close to Wy. felicia, is described. The new species can be distinguished by morphological characters of the male genitalia, larva and pupa. more...

Purpose: The present study aims a) to assess the agreement between the measured resting metabolic rate (RMR) using indirect calorimetry and different predictive equations (predicted RMR), and b) to propose and cross-validate two new predictive equations for estimating the RMR in high-level athletes., Methods: The RMR of 102 athletes (44 women) was assessed using indirect calorimetry, whereas the body composition was assessed using skinfolds. Comparisons between measured and predicted RMR values were performed using one-way ANOVA. Mean difference, root mean square error (RMSE), simple linear regression, and Bland-Altman plots were used to evaluate the agreement between measured and predicted RMR. The accuracy of predictive equations was analyzed using narrower and wider accuracy limits (±5% and ±10%, respectively) of measured RMR. Multiple linear regression models were employed to develop the new predictive equations based on traditional predictors (equation 1) and the stepwise method (equation 2)., Results: The new equations 1 and 2 presented good agreement based on the mean difference (3 and -15 kcal·d -1 ), RMSE (200 and 192 kcal·d -1 ), and R2 (0.71 and 0.74), respectively, and accuracy (61% of subjects between the limit of ±10% of measured RMR). Cunningham's equation provided the best performance for males and females among the existing equations, whereas Jagim's equation showed the worst performance for males (mean difference = -335 kcal·d -1 ; RMSE = 386 kcal·d -1 ). Compared with measured RMR, most predictive equations showed heteroscedastic distribution (linear regression's intercept and slope significantly different from zero; P ≤ 0.05), mainly in males., Conclusions: The new proposed equations can estimate the RMR in high-level athletes accurately. Cunningham's equation is a good option from existing equations, and Jagim's equation should not be used in high-level male athletes., (Copyright © 2022 by the American College of Sports Medicine.) more...

Altered fear learning is a strong behavioral component of anxiety disorders such as post-traumatic stress disorder (PTSD). Recent efforts have attempted to combine exposure therapies with drugs that target fear memory retrieval and memory reconsolidation, in order to improve treatment efficacy. The noradrenergic (NA) signaling system is of particular interest, due to its role in regulating the stress response and its involvement in fear and learning processes. Importantly, propranolol (P), a non-selective β-adrenergic antagonist, has shown the potential in decreasing exaggerated fear in both humans and animal models. In a previous study, we utilized an activity-dependent tagging murine model to determine the neural mechanisms by which propranolol attenuates learned fear. We found that propranolol acutely decreased memory trace reactivation specifically in the dorsal dentate gyrus (dDG), but not in CA3 or CA1. Here, we extended our previous study by investigating whether propranolol additionally altered activity in the hilus, a polymorphic layer that consists of neurons, mossy cells, and GABAergic interneurons. We found that propranolol acutely reduced overall hilar activity in both the dorsal and ventral hilus. Moreover, we report that propranolol significantly altered the activity of parvalbumin (PV) + cells in the ventral (vDG), but not dorsal DG (dDG). Together, these results suggest that a β-adrenergic blockade may affect the activity of excitatory and inhibitory cell types in the hilar layer of the DG, and that these alterations may contribute to manipulating fear memory traces., Competing Interests: SL, VP, and CD were employed by Research Foundation for Mental Hygiene, Inc. The remaining 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 Leal Santos, Chen, Pereira, Pham and Denny.) more...

This study offers a novel oral pregabalin (PG)-loaded drug delivery system based on chitosan and hypromellose phthalate-based polymeric nanocomposite in order to treat neuropathic pain (PG-PN). PG-PN has a particle size of 432 ± 20 nm, a polydispersity index of 0.238 ± 0.001, a zeta potential of +19.0 ± 0.9 mV, a pH of 5.7 ± 0.06, and a spherical shape. Thermal and infrared spectroscopy confirmed nanocomposite generation. PG-PN pharmacokinetics was studied after a single oral dose in male Wistar rats. PG-PN showed greater distribution and clearance than free PG. The antinociceptive effect of PG-PN in neuropathic pain rats was tested by using the chronic constriction injury model. The parameter investigated was the mechanical nociceptive threshold measured by the von Frey filaments test; PG-PN showed a longer antinociceptive effect than free PG. The rota-rod and barbiturate sleep induction procedures were used to determine adverse effects; the criteria included motor deficit and sedative effects. PG-PN and free PG had plenty of motors. PG-PN exhibited a less sedative effect than free PG. By prolonging the antinociceptive effect and decreasing the unfavorable effects, polymeric nanocomposites with pregabalin have shown promise in treating neuropathic pain. more...

Paulownin, a natural compound obtained from the tree Tecoma stans var. stans , was chemically modified by alkylation of its hydroxyl position. Thirteen novel lignans derivatives synthesized via a copper-catalyzed cycloaddition (CuAAC), known as click reaction, using different organic azides and lignan terminal alkyne. Characterization by mass spectrometry, NMR ( 1 H and 13 C) and infrared spectroscopy. These novel molecules were submitted to biological tests, using the MTT colorimetric technique aiming at the verification of their antitumor properties with six different cells lines. Biological evaluation was satisfactory and one of compounds showed selectivity index ten times higher than podophyllotoxin. more...

Psoriasis is an autoimmune, inflammatory and chronic skin disease in which cell growth and proliferation are increased, causing erythema, lesions and skin's peeling. Oral methotrexate (MTX) is the first-choice drug when phototherapy or retinoid treatment are not effective. Topical administration can be advantageous to better orientate the drug's delivery; however, the stratum corneum performs as a barrier for hydrofilic drugs penetration. This study sought to evaluate two different types of vehicles for MTX on the psoriasis treatment - hydrogel and liquid crystal systems (LCs). Lamellar and hexagonal liquid crystalline phases were selected from a ternary phase diagram based on polysorbate 80, isopropyl miristate and water. The hydrogel was based on alkylated carbomer (ACH). Rheological analysis showed ACH was more elastic than lamellar and hexagonal phases. ACH interacted better with pig skin than LCs in bioadhesion assay. Preclinical study revealed the ACH decreased inflammation in mice with induced psoriasis, being as effective as dexamethasone to regulate epidermis thickness, COX-2 and myeloperoxidase activity and TNF-α level, while LCs demonstrated inflammatory effect. Therefore, MTX-loaded hydrogel based platforms are indicated for local treatment of psoriasis and present great potential for further studies., (Copyright © 2021 Elsevier B.V. All rights reserved.) more...

This work proposes new methotrexate (MTX) loaded drug delivery systems (DDS) to treat rheumatoid arthritis via the intra-articular route: a poloxamer based thermosensitive hydrogel (MTX-HG), oligochitosan and hypromellose phthalate-based polyelectrolyte complexes (MTX-PEC) and their association (MTX-PEC-HG). MTX-PEC showed 470 ± 166 nm particle size, 0.298 ± 0.108 polydispersity index, +26 ± 2 mV and 74.3 ± 5.8% MTX efficiency entrapment and particle formation was confirmed by infrared spectroscopy and thermal analysis. MTX-HG and MTX-PEC-HG gelled at 36.7°C. MTX drug release profile was prolonged for MTX-HG and MTX-PEC-HG, and faster for MTX-PEC and free MTX. The in vivo effect of the MTX-DDSs systems was evaluated in induced arthritis rats as single intra-articular dose. The assessed parameters were the mechanical nociceptive threshold, the plasmatic IL-1β level and histological analysis of the tibiofemoral joint. MTX-HG and MTX-PEC-HG performance were similar to free MTX and worse than oral MTX, used as positive control. All DDSs showed some irritative effect, for which further studies are required. MTX-PEC was the best treatment on recovering cartilage damage and decreasing allodynia. Thus, MTX-PEC demonstrated potential to treat rheumatoid arthritis, with the possibility of decreasing the systemic exposure to the drug., (Copyright © 2021 Elsevier B.V. All rights reserved.) more...

Although nanoparticles, polymeric micelles, liposomes, nanoemulsions, and microemulsions were extensively evaluated as formulations for nasal administration of drugs, lyotropic liquid crystal (LLC) mesophases have been few studied. The phase transition from a low-viscosity microemulsion to a more viscous LLC may improve the mucoadhesion of the formulation. Donepezil is a drug administered orally in the treatment of Alzheimer's disease, and with gastrointestinal side effects that are typical of acetylcholinesterase inhibitors. Based on this, donepezil administration by nasal pathway using a mucoadhesive LLC may be a feasible alternative. A colloidal formulation was selected from a ternary diagram, combining CETETH-10, oleic acid, and water (40:45:15, w/w). Donepezil was incorporated into the formulation, and the characterisation included in vitro studies, such as mucoadhesion and drug release. Pharmacokinetics in Wistar rats included evaluations by the nasal pathway with donepezil incorporated into microemulsion. A phase transition from an isotropic to an anisotropic system was observed after the swelling of the microemulsion with artificial nasal fluid (12-20 %). The release of donepezil in vitro occurred in a sustained manner. Significant levels of donepezil were achieved in the brain after nasal administration of the microemulsion, as a promising strategy for the treatment of Alzheimer's disease., (Copyright © 2021 Elsevier B.V. All rights reserved.) more...

The aim of this study was to compare the biometric testicular characteristics, skin thickness and haemodynamics of the testicular artery of 12- and 24-month-old bulls using Doppler ultrasonography, the study was conducted using 48 indicus-taurus animals. The scrotal circumference (SC) and biometry characteristics of the bulls were measured to calculate the testicular volume. Doppler ultrasonography was used to obtain the haemodynamic values of the testicular artery. The skin thickness and volume were lower (p<.01) in the younger bulls (12 months:4.68 ± 0.68 mm; 168.76 ± 47.96 cm 3 ) versus 24 months (5.05 ± 0.89; 499.73 ± 129.24 cm 3 ) animals (p<.01). During diastole, mean velocity was lower in the 12 months (7.98 ± 3.83) than in the 24 months (11.37 ± 4.15) animals (p <.05). The 12-month-old animals had higher pulsatility and resistivity indices (0.49 ± 0.02; 0.51 ± 0.20) compared to the 24-month-old animals (0.32 ± 0.16; 0.40 ± 0.15) (p < .05). The final testicular end velocity was lower in animals with long/moderate-shaped (L/M) (7.31 ± 2.91) than in those moderate/oval-shaped (M/O) (11.48 ± 3.88) testicles (p < .05). Animals with L/M testes presented higher pulsatility values and resistivity indices (0.51 ± 0.05; 0.55 ± 0.04) compared to animals with M/O shape (0.29 ± 0.20; 0.36 ± 0.15). We showed that the blood flow of the supra testicular artery between the two evaluated ages differed, and that 24-month-old bulls presented better thermoregulation capacity. Animals with a long/moderate testicular format presented a greater vascular resistance, which was imposed on the blood flow due to the anatomical differences in the testicular artery, resulting in lower velocity, and indicating better heat dissipation in this format., (© 2021 Wiley-VCH GmbH.) more...

Acyclovir is an antiviral drug poorly absorbed in the gastrointestinal tract due to its hydrophilicity, with low oral bioavailability (~20%). Although acyclovir is prescribed in the management of herpes simplex encephalitis (HSE), the disease has a poor prognosis, particularly if the treatment is delayed, reaching mortality rates of 70% if left untreated. Thus, high acyclovir doses are administered by intravenous (IV) infusion, usually at a dosage of 10 mg kg -1 8-hourly in adults with normal renal function. However, the mortality related to HSE treated with acyclovir remains high (~20%) and permanent sequelae are commonly reported after 1 year (~50%). This review analyzed clinical trials following IV acyclovir administration. Novel insights aiming to improve drug bioavailability were reviewed, including acyclovir or its prodrugs, leading to the systemic distribution of the drug or drug targeting. Much research effort has been made to improve antiviral therapy, searching for delivery systems increasing acyclovir bioavailability by non-invasive pathways, such as oral and nasal pathways, or parenterally administered nanotechnology-based systems leading to drug targeting. Nanocarriers administered by non-invasive pathways represent feasible alternatives to treat HSE, even though not be industrially manufactured yet., (Copyright © 2021 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.) more...

The therapeutic potential of cannabidiol (CBD) has been explored to treat several pathologies, including those in which pain is prevalent. However, the oral bioavailability of CBD is low owing to its high lipophilicity and extensive first-pass metabolism. Considering the ability of the nasal route to prevent liver metabolism and increase brain bioavailability, we developed nanostructured lipid carriers (NLCs) for the nasal administration of CBD. We prepared particles with a positively charged surface, employing stearic acid, oleic acid, Span 20 Ⓡ , and cetylpyridinium chloride to obtain mucoadhesive formulations. Characterisation of the CBD-NLC dispersions showed uniform nano-sized particles with diameters smaller than 200 nm, and high drug encapsulation. The mucoadhesion of cationic particles has been related to interactions with negatively charged mucin. Next, we added in-situ gelling polymers to the CBD-NLC dispersion to obtain a CBD-NLC-gel. A thermo-reversible in-situ forming gel was prepared by the addition of Pluronics Ⓡ . CBD-NLC-gel was characterised by its gelation temperature, rheological behaviour, and mucoadhesion. Both formulations, CBD-NLC and CBD-NLC-gel, showed high mucoadhesion, as assessed by the flow-through method and similar in vitro drug release profiles. The in vivo evaluation showed that CBD-NLC dispersion (without gel), administered intranasally, produced a more significant and lasting antinociceptive effect in animals with neuropathic pain than the oral or nasal administration of CBD solution. However, the nasal administration of CBD-NLC-gel did not lessen mechanical allodynia. These findings demonstrate that in-situ gelling hydrogels are not suitable vehicles for highly lipophilic drugs such as CBD, while cationic CBD-NLC dispersions are promising formulations for the nasal administration of CBD., (Copyright © 2021. Published by Elsevier B.V.) more...

The present study aimed to propose and assess the physiological responses of a novel graded karate test. Ten male national-level karate athletes (age 26 ± 5 yrs; body mass 69.5 ± 11.6 kg; height 1.70 ± 0.09 m) performed two exercise tests (separated by 2-7 days): 1) a running-based cardiopulmonary exercise test; 2) a graded karate test. The cardiopulmonary exercise test was comprised of an individualized ramp protocol for treadmill running, and the graded karate test was comprised of a sequence of 'kisami-gyaku-zuki" punching at a fixed frequency of a stationary target that becomes progressively distant. Cardiorespiratory responses, blood lactate concentration, and perceived exertion were measured. A verification phase was also performed in both tests to confirm the maximal physiological outcomes. The graded karate test evoked similar maximal responses to the running protocol: V̇O 2 (57.4 ± 5.1 vs 58.3 ± 3.5 mL·kg -1 ·min -1 ; p = 0.53), heart rate (192 ± 6 vs 193 ± 10]beats.min -1 ; p = 0.62) and blood lactate (14.6 ± 3.4 vs 13.1 ± 3.0 mmol·L -1 ; p = 0.14) with a shorter duration (351 ± 71 vs 640 ± 9 s; p < 0.001). Additionally, the graded karate test evoked higher V̇O 2 (72.6 ± 6.5 vs 64.4 ± 4.3 %V̇O 2MAX ; p = 0.005) and heart rate (89.4 ± 4.6 vs 77.3 ± 7.2 %HR MAX p < 0.001) at the ventilatory threshold and a higher heart rate (97.0 ± 2.4 vs 92.9 ± 2.2 %HR MAX ; p = 0.02) at the respiratory compensation point. Incremental and verification phases evoked similar responses in V̇O 2 and minute-ventilation during both tests. This novel displacement-based sport-specific test evoked similar maximal and higher submaximal responses, indicating a superior pathway to assess karate athletes., (© Journal of Sports Science and Medicine.) more...

A viscous solution of low molecular weight chitosan (CH) at 5% w/v (10.2 kDa, 75 % deacetylated, 1451 cP at 25 °C) was associated with a microemulsion (ME) that undergoes a phase transition after water absorption in situ (≈28 % w/w), forming a more viscous liquid crystal, which was potentially evaluated as a topical vehicle. The ME was selected from a phase diagram, selecting a composition based on Tween® 80 (52 %), myristate isopropyl (28 %), and the aqueous phase (water and polyethylene glycol 400, 60:40 w/w) (20 %), which was after replaced by CH and herbal medicines (HM). HM are alternatives to treat candidiasis, and Stryphnodendron adstringens shell extract, characterized by molecular networking, and Melaleuca alternifolia Chell essential oil (46 % of terpinen-4-ol), showed in vitro activity against Candida albicans. Associating CH in ME improved the mechanical properties of the topical formulation, as adhesiveness, which is an advantageous feature for the topical treatment of vulvovaginal candidiasis., (Copyright © 2020 Elsevier Ltd. All rights reserved.) more...

Purpose: Considering the current recommendation of the World Health Organization to replace sputum smear microscopy with Xpert MTB/RIF as an initial diagnostic test for tuberculosis (TB), and that culture takes time to provide results, the cycle threshold (C T ) of the Xpert test may be the only way to assess bacillary load. The objective of this study is to evaluate the association of bacillary load, measured by the Xpert C T , with the TB treatment outcomes., Methods: In cohort study, Xpert C T values were evaluated in cured and non-cured (failure and death) patients. Multivariate analysis was performed to evaluate if C T is independently associated with TB treatment outcomes., Results: During this study period, 155 patients (84 cured and 71 non-cured) met the inclusion and were included in the analysis. The mean C T value for Xpert MTB/RIF test was 20.7 ± 5.6 in cured patients and 17.1 ± 5.6 in non-cured patients (p < 0.0001). Previous TB was more frequent in non-cured (28.2%) than in cured patients (7.1%) (p < 0.0001). Non-cured patients were younger than cured ones (37.1 ± 13.3 vs 43.6 ± 16.2; p = 0.006). HIV was more frequent in non-cured (28.2%) than in cured patients (15.5%), although this difference was not statistically significant (p = 0.054). In multivariate analysis, C T values, age, previous TB, and HIV were independently associated with non-cure., Conclusions: Lower Xpert MTB/RIF C T values were independently associated with worse treatment outcomes. The information from even a single test performed before starting treatment proved to be a relatively good predictor of TB treatment outcome. more...

The use of anticorrosive coatings has been a powerful method to be applied on the surface of metallic materials to mitigate the corrosive process. In this study, the focus is composite coatings that are commonly used on the internal surface of storage tanks in petrochemical industries. The development of non-destructive methods for inspection of faults in this field is desired due to unhealthy access and mainly because undercoating corrosion is difficult to detect by visual inspection. Pulsed thermography (PT) was employed to detect undercoating corrosion and adhesion loss of anticorrosive composite coatings defects. Additionally, a computational simulation model was developed to complement the PT tests. According to the experimental results, PT was able to detect all types of defects evaluated. The results obtained by computational simulation were compared with experimental ones. Good correlation (similarity) was verified, regarding both the defect detection and thermal behavior, validating the developed model. Additionally, by reconstructing the thermal behavior according to the defect parameters evaluated in the study, it was estimated the limit of the remaining thickness of the defect for which it would be possible to obtain its detection using the pulsed modality., Competing Interests: The authors declare no conflict of interest more...

The oviposition behavior of mosquitoes varies between species. We documented the unusual mechanism of egg laying in the mosquito Sabethes albiprivus Theobald with the aid of high speed video recordings in the laboratory. A sapucaia (Lecythis pisonis Camb.) nut oviposition trap, described herein, was used to simulate a tree hole with a small opening, which is the natural larval habitat of Sa. albiprivus. We showed that females approach the opening and perform a sequence of rapid, short up-and-down flights before egg laying. At this time, the egg is already visible externally, being held at the very tip of the abdomen. Females catapult one egg at a time by rapidly curling their abdomen downward, sending the egg through the opening while their legs are positioned in different configurations throughout the event. The estimated velocity of the catapulted eggs was almost 1 m/s. more...

Background: Plant species from the genus Tecoma are found in tropical and subtropical regions around the world. Some of them are grown as ornamental plants and others can be used as medicinal plants. In the present study, ethanolic extracts from trunks and leaves of Tecoma species were tested in vitro using assays against the Zika virus., Methods: There was a total of 8 extracts obtained from different anatomical parts of three Tecoma species. The Tecoma castaneifolia, T. garrocha, T. stans var. angustata and T. stans var. stans were prepared by percolation with ethanol. The antiviral activity was assayed in vitro against the Zika virus by the MTT colorimetric method (n = 3). The UPLC-DAD-MS analysis of ethanolic extracts was performed from all the studied species. The biofractionation of T. stans var. stans trunk extract using different separation techniques led to the isolation of crenatoside compound., Results: Ethanolic extract from Tecoma species leaves were more active against the Zika virus (EC 50 149.90 to 61.25 μg/mL) when compared to the trunk extracts tested (EC 50 131.0 to 66.79 μg/mL and two were not active). The ethyl acetate and aqueous fractions obtained from T. stans var. stans trunk were active against the Zika virus with EC 50 values of 149.90 and 78.98 μg/mL, respectively. Crenatoside is a phenylethanoid glycoside isolated from the ethyl acetate of T. stans var. stans trunk extract. This compound was tested and exhibited EC 50 34.78 μM (21.64 μg/mL), thus demonstrating a better result than the original ethanolic extracts as well as others extracts of Tecoma species, and it was more active than the positive control, ribavirin (386.84 μM). Furthermore, its selectivity index was at least 2.5 times higher than the tested ethanolic extracts and 11.1 times more potent than ribavirin., Conclusion: The Tecoma species demonstrated interesting in vitro activity against the Zika virus. The crenatoside, phenylethanoid glycoside that was for the first time isolated from Tecoma stans var. stans, exhibited a potent and relevant anti-Zika virus activity, being more active than ribavirin (positive control). The data show that crenatoside, was a promising compound with in vitro antiviral activity against the Zika virus. more...

Background: Although a highly common practice in hospital care, tablet splitting can cause dose variation and reduce drug stability, both of which impair drug therapy., Objective: To determine the overall prevalence of tablet splitting in hospital care as evidence supporting the rational prescription of split tablets in hospitals., Methods: Data collected from inpatients' prescriptions were analyzed using descriptive statistics and used to calculate the overall prevalence of tablet splitting and the percentage of split tablets that had at least one lower-strength tablet available on the market. The associations between the overall prevalence and gender, age, and hospital unit of patients were also assessed. The results of laboratory tests, performed with a commercial splitter, allowed the calculation of the mass loss, mass variation, and friability of the split tablets., Results: The overall prevalence of tablet splitting was 4.5%, and 78.5% of tablets prescribed to be split had at least one lower-strength tablet on the market. The prevalence of tablet splitting was significantly associated with the patient's age and hospital unit. Laboratory tests revealed mean values of mass loss and variation of 8.7% (SD 1.8) and 11.7% (SD 2.3), respectively, both of which were significantly affected by the presence of coating and scoreline. Data from laboratory tests indicated that the quality of 12 of the 14 tablets deviated in at least one parameter examined., Conclusions: The high percentage of unnecessary tablet splitting suggests that more regular, rational updates of the hospital's list of standard medicines are needed. Also, inappropriate splitting behavior suggests the need to develop tablets with functional scores., Competing Interests: CONFLICT OF INTEREST No conflicts of interest have been declared., (Copyright: © Pharmacy Practice and the Authors.) more...

Seminal plasma (SP) contributes to sperm physiology and metabolism, prevents premature capacitation, and protects sperm against oxidative stress. In order to evaluate the impact of heat stress in the semen of tropically adapted Brangus breed and in their seminal plasma proteome, we studied the effects of scrotal insulation for 72 h. Semen samples from six bulls, between 7 and 8 years of age, were collected prior to scrotal insulation (pre-insulation), and at 4 and 11 wk after insulation. Seminal plasma samples were analyzed by 2D SDS-PAGE and liquid chromatography coupled with mass spectrometry (LC-MS/MS). Insulation caused decrease in vigour, gross and total motility after 4 wk of scrotal insult (P < 0.001). Total defects in sperm were higher after 4 wk compared to pre-insulation and 11 wk after scrotal insulation (P < 0.001). The analysis of the 2D protein profile of the SP resulted in the identification 183 unique protein spots in all gels evaluated. There was no difference in mean number of protein spots amongst time points. Eight protein spots were more abundant in SP after scrotal insulation, returning to the same expression level at 11 wk post-insulation. One spot had higher abundance at 11 wk post-insulation, and one spot had decreased abundance 4 wk after insulation. The ten protein spots with differential abundance amongst time points were identified as Seminal plasma protein PDC-109, Seminal plasma protein A3, Seminal plasma protein BSP-30 kDa, Spermadhesin-1 and Metalloproteinase inhibitor 2. The validation of these five proteins as biomarkers for thermal testicular stress in Brangus breed would allow the development of new biotechnologies that could improve bovine semen analysis in breeding systems in tropical and subtropical conditions. A close association between the identified BSP and Spermadhesin-1 was evidenced in protein-protein interaction analysis. Based on gene ontology analysis, variation in sperm function after insulation could be explained by variation in the expressed proteins in the SP. Further studies are required to verify if these proteins could be used as biomarkers for the identification of bulls with increased seminal resistance to heat stress in Brangus breed., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest that may have influenced that discussion presented herein., (Copyright © 2020 Elsevier Inc. All rights reserved.) more...

The present study assessed the exposure to methylparaben (MP) and propylparaben (PP) from antiperspirants in serum of 24 women aged 20-30 years old and an in vitro skin assay. An effective liquid chromatography-tandem mass spectrometry method for the determination of MP and PP levels in serum was developed and validated in the range of 10-100 μg/L; the method was fast, simple, sensitive, linear, precise, and accurate. In addition, a simple and rapid liquid chromatography-ultraviolet detection method for the determination of MP and PP levels in antiperspirants was developed and validated in the range of 2-26 mg/L, which presented satisfactory linearity, precision, and accuracy. Using these two methods, 20 commercial antiperspirants were evaluated, and only three showed MP and PP in the formulation. The antiperspirant containing 0.2% and 0.1% w/w MP and PP, respectively, was given to the volunteers, to estimate the internal dose, and submitted to a pig ear skin permeation assay in Franz diffusion cells, presenting a permeation flux of 32% for MP and 71% for PP. In this assay, both MP and PP permeated the skin; however, there was no correlation between antiperspirant use and paraben serum concentration in the volunteers. Graphical abstract. more...

Introduction: Since 2018, World Health Organization (WHO) recommended the Xpert MTB/RIF Ultra use for pulmonary and extrapulmonary TB diagnosis, and suggested that Xpert Ultra should be tested in various populations, with different geographical and epidemiological settings., Methods: Cross-sectional study with prospective data collection. Outpatients aged >18 years with respiratory symptoms suggestive of pulmonary TB were invited to participate. Sensitivity, specificity, positive and negative predictive values of the test were calculated and compared with the traditional Xpert MTB/RIF., Results: During the study period, 180 patients met the inclusion and were included in the analysis. Xpert MTB/RIF Ultra test was positive in 33 patients (18.3%), and RIF resistance was detected in 1 (3.1%) patient. Considering culture as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of Xpert MTB/RIF Ultra were 100.0% (95% CI 85.2-100.0), 93.6% (95% CI 88.6-96.9), 69.7% (95% CI 55.8-80.7), and 100.0% (95% CI 87.2-100.0), respectively. The area under the ROC curve was 0.97 for the Xpert MTB/RIF Ultra test (95% CI 0.93 to 0.99; p < 0.0001). There was no difference statistically significant between sensitivities and specificities of Xpert MTB/RIF and Xpert MTB/RIF Ultra (p > 0.05)., Conclusions: This is the first study in Brazil to evaluate the accuracy of Xpert MTB/RIF Ultra in individuals with presumptive pulmonary TB. The test showed an excellent sensitivity and a high specificity, demonstrating that it is a useful tool for pulmonary TB diagnosis., 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 © 2020 Elsevier Ltd. All rights reserved.) more...

The identification of new therapeutics to treat leishmaniasis is desirable, since available drugs are toxic and present high cost and/or poor availability. Therefore, the discovery of safer, more effective and selective pharmaceutical options is of utmost importance. Efforts towards the development of new candidates based on molecule analogs with known biological functions have been an interesting and cost-effective strategy. In this context, quinoline derivatives have proven to be effective biological activities against distinct diseases. In the present study, a new chloroquinoline derivate, AM1009, was in vitro tested against two Leishmania species that cause leishmaniasis. The present study analyzed the necessary inhibitory concentration to preclude 50% of the Leishmania promastigotes and axenic amastigotes (EC 50 value), as well as the inhibitory concentrations to preclude 50% of the murine macrophages and human red blood cells (CC 50 and RBC 50 values, respectively). In addition, the treatment of infected macrophages and the inhibition of infection using pre-treated parasites were also investigated, as was the mechanism of action of the molecule in L. amazonensis. To investigate the in vivo therapeutic effect, BALB/c mice were infected with L. amazonensis and later treated with AM1009. Parasitological and immunological parameters were also evaluated. Clioquinol, a known antileishmanial quinoline derivate, and amphotericin B (AmpB), were used as molecule and drug controls, respectively. Results in both in vitro and in vivo experiments showed a better and more selective action of AM1009 to kill the in vitro parasites, as well as in treating infected mice, when compared to results obtained using clioquinol or AmpB. AM1009-treated animals presented significantly lower average lesion diameter and parasite burden in the infected tissue and organs evaluated in this study, as well as a more polarized antileishmanial Th1 immune response and low renal and hepatic toxicity. This result suggests that AM1009 should be considered a possible therapeutic target to be evaluated in future studies for treatment against leishmaniasis., (Copyright © 2019 Elsevier B.V. All rights reserved.) more...

Scrotal circumference (SC) is considered a useful tool for predicting age at puberty and is performed to improve the reproductive performance in beef cattle industry. We aimed to fit several nonlinear mixed models for SC measurements of five different breeds to better predict testicular growth. Data of SC (cm), body weight (BW; kg), and age (A; days), farm location, sire and dam, and birth dates of 169,094 beef bulls were collected from five breeds: Nelore (N) (n = 110,814); Angus (AA) (n = 6541); Brangus (BA) (n = 42,910); Polled Hereford and Hereford (HH) (n = 4640); and Braford (BH) (n = 7480). Data comprise a total of 8640 sires and 115,172 dams and grouped in 2908 contemporary groups (CG). The full model development for SC was defined as: SC = CG + A + A*A + BW + BW*BW + Ɛ. Bulls from HH (34.1 ± 3.2) and AA (33.5 ± 3.0) had the highest value of SC, followed by BH (32.2 ± 3.7), BA (30.6 ± 4.1), and N (26.9 ± 3.6). There was a curvilinear effect of BW on the SC measurements of HH and AA bulls, reaching the maximum point around 600 kg, whether both breeds presented a similar testicular growth pattern. In British breeds, inflection points of average daily SC growth of 0.039 and 0.042 cm/kg were obtained from 700 kg HH and 600 kg AA bulls, respectively. Scrotal circumference values of 0.042 and 0.046 cm/kg reaching the maximum growth point at 450 kg BW were obtained for BH and BA bulls, respectively. We also observed SC values of 0.044 and 0.048 cm/d reaching the maximum growth point at 550 d of age for BH and BA bulls, respectively. Thus, estimate testicular size at maturity should be measured between 500 and 600 kg BW in British genotypes and between 550 and 600 d in Bos indicus and crossbreeds animals. Therefore, SC adjustment can be used by breed-specific criteria associated with BW and/or age to determine testis growth as a selection criterion in beef cattle breeding programs., (Copyright © 2019 Elsevier Inc. All rights reserved.) more...