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Reporter alleles are essential for advancing research with human induced pluripotent stem cells (hiPSCs), notably in developmental biology and disease modeling. This study investigates the state-of-the-art gene-editing techniques tailored for generating reporter alleles in hiPSCs, emphasizing their effectiveness in investigating cellular dynamics and disease mechanisms. Various methodologies, including the application of CRISPR/Cas9 technology, are discussed for accurately integrating reporter genes into the specific genomic loci. The synthesis of findings from the studies utilizing these reporter alleles reveals insights into developmental processes, genetic disorder modeling, and therapeutic screening, consolidating the existing knowledge. These hiPSC-derived models demonstrate remarkable versatility in replicating human diseases and evaluating drug efficacy, thereby accelerating translational research. Furthermore, this review addresses challenges and future directions in refining the reporter allele design and application to bolster their reliability and relevance in biomedical research. Overall, this investigation offers a comprehensive perspective on the methodologies, applications, and implications of reporter alleles in hiPSC-based studies, underscoring their essential role in advancing both fundamental scientific understanding and clinical practice.

Objective: The aim of this study was to analyze the factors associated with elder abuse according to the levels of social determinants., Methodology: This is a quantitative and multicentric study, with a cross-sectional cut. It was developed in two teaching hospitals in Paraíba, Brazil, with 323 older adults, from July 2019 to February 2020. Data were collected using the Hwalek-Sengstock Elder Abuse Screening Test and Conflict Tactics Scale-1 and then analyzed using descriptive and inferential statistics., Results: There was a significant association between risk for violence and female gender (p = 0.004), residing with grandchildren (p = 0.025), and having four or more comorbidities (p < 0.00). Physical violence was associated with income (p = 0.048). A positive correlation was observed between the number of comorbidities and the risk for violence score (p < 0.001), psychological violence (p = 0.004), and physical violence (p = 0.005). The probability of presenting a risk to violence increased by 2.08 times for women, 1.03 times for those who were illiterate, and 7.03 times for those with four or more comorbidities., Conclusion: The social determinants of health that integrate the macrosystem, such as income and number of comorbidities, correlate with situations of violence., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 International Association of Forensic Nurses.)

Canine leishmaniasis (CanL) caused by Leishmania infantum commonly progresses with renal and ophthalmic lesions associated with active systemic disease. As chronic inflammation related to immune complex deposits is a pathophysiological factor in the development of both glomerulonephritis and uveitis, we aimed to evaluate renal and ocular histopathological lesions and analyze whether they were related to each other and the clinical degree of the disease. For that, we evaluated 15 dogs from CanL-endemic areas. L. infantum PCR-positive dogs were studied according to disease severity into two different groups: Group-1 (G1) had data from seven dogs with mild to moderate CanL and no history of treatment, and G2 was formed with eight dogs with severe to terminal disease that had not responded to CanL treatment. Histopathological analysis of kidneys showed higher frequencies and intensities of glomerular basement membrane thickening (p = 0.026), deposits in glomeruli (p = 0.016), epithelial necrosis (p = 0.020), tubular dilatation (p = 0.003) and interstitial fibrosis (p = 0.04) in G2 dogs than in G1 dogs. Surprisingly, the histopathology of eye bulbs showed a higher frequency and intensity of retinitis (p = 0.019) in G1 dogs than in G2 dogs. The comparative analysis showed that there was no correspondence between histopathological findings in kidneys versus eyes in milder or more severe CanL. Our findings suggested that (1) clinically undetectable eye alterations can be more precocious than those in kidneys in the development of CanL, and (2) the lower frequency of eye lesions and higher frequency of renal lesions in dogs with terminal disease even after treatment indicate that therapy may have been effective in reducing CanL-associated ophthalmic disease but not proportionally in reducing kidney disease., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Maternal Zika virus (ZIKV) infection during pregnancy has been associated with severe intrauterine growth restriction (IUGR), placental damage, metabolism disturbances, and newborn neurological abnormalities. Here, we investigated the impact of maternal ZIKV infection on placental nutrient transporters and nutrient-sensitive pathways. Immunocompetent (C57BL/6) mice were injected with Low (10 3 PFU-ZIKV PE243 ) or High (5 × 10 7 PFU-ZIKV PE243 ) ZIKV titers at gestational day (GD) 12.5, and tissue was collected at GD18.5 (term). Fetal-placental growth was impaired in male fetuses, which exhibited higher placental expression of the ZIKV infective marker, eukaryotic translation initiation factor 2 (eIF2α), but lower levels of phospho-eIF2α. There were no differences in fetal-placental growth in female fetuses, which exhibited no significant alterations in placental ZIKV infective markers. Furthermore, ZIKV promoted increased expression of glucose transporter type 1 (Slc2a1/Glut1) and decreased levels of glucose-6-phosphate in female placentae, with no differences in amino acid transport potential. In contrast, ZIKV did not impact glucose transporters in male placentae but downregulated sodium-coupled neutral amino acid 2 (Snat2) transporter expression. We also observed sex-dependent differences in the hexosamine biosynthesis pathway (HBP) and O-GlcNAcylation in ZIKV-infected pregnancies, showing that ZIKV can disturb placental nutrient sensing. Our findings highlight molecular alterations in the placenta caused by maternal ZIKV infection, shedding light on nutrient transport, sensing, and availability. Our results also suggest that female and male placentae employ distinct coping mechanisms in response to ZIKV-induced metabolic changes, providing insights into therapeutic approaches for congenital Zika syndrome., (© 2024 Federation of American Societies for Experimental Biology.)

Genomic DNA methylation patterns play a crucial role in the developmental processes of plants and mammals. In this study, we aimed to investigate the significant effects of epigenetic mechanisms on the development of soybean seedlings and metabolic pathways. Our analyses show that 5-azaC-treatment affects radicle development from two Days After Imbibition (DAI), as well as both shoot and root development. We examined the expression levels of key genes related to DNA methylation and demethylation pathways, such as DRM2, which encodes RNA-directed DNA Methylation (RdDM) pathway, SAM synthase, responsible for methyl group donation, and ROS1, a DNA demethylase. In treated seedling roots, we observed an increase in DRM2 expression and a decrease in ROS1 expression. Additionally, 5-azaC treatment altered protein accumulation, indicating epigenetic control over stress response while inhibiting nitrogen assimilation, urea cycle, and glycolysis-related proteins. Furthermore, it influenced the levels of various phytohormones and metabolites crucial for seedling growth, such as ABA, IAA, ethylene, polyamines (PUT and Cad), and free amino acids, suggesting that epigenetic changes may shape soybean responses to pathogens, abiotic stress, and nutrient absorption. Our results assist in understanding how hypomethylation shapes soybean responses to pathogens, abiotic stress, and nutrient absorption crucial for seedling growth, suggesting that the plant's assimilation of carbon and nitrogen, along with hormone pathways, may be influenced by epigenetic changes., (© 2024 Scandinavian Plant Physiology Society.)

Objective: This systematic review accompanied by a meta-analysis aimed to estimate the prevalence of syphilis in pregnant women in Brazil and describe its associated factors., Methods: Following the establishment the search strategies and the registration of the review protocol in PROSPERO, we conducted a search for relevant articles in the Pubmed, LILACS, Science Direct, SciELO and Web of Science databases. Our inclusion criteria were cross-sectional studies published between 2005 and 2023, with no language restrictions. The combined prevalence of syphilis infection was estimated using the random effects model in the R Software with a 95% confidence interval (95% CI) and p < 0.01 as statistically significant., Results: A total of 24 articles were recruited, which together investigated 221,884 women. The combined prevalence of syphilis in pregnant women in Brazil was 1.79% (95% CI: 1.24-2.57%), and the main factors associated with its occurrence were black and brown skin color, low education and factors related to the partner., Conclusion: There was a high prevalence of syphilis in pregnancy in Brazil, mainly associated with socioeconomic factors., Competing Interests: Conflicts to interest: none to declare., (© 2024. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved.)

Disruption of the brain serotoninergic (5-HT) system during development induces long-lasting changes in molecular profile, cytoarchitecture, and function of neurons, impacting behavioral regulation throughout life. In male and female rats, we investigate the effect of neonatal tryptophan hydroxylase (TPH) inhibition by using para-chlorophenylalanine (pCPA) on the expression of 5-HTergic system components and neuropeptides related to adolescent social play behavior regulation. We observed sex-dependent 5-HT levels decrease after pCPA-treatment in the dorsal raphe nucleus (DRN) at 17 and 35 days. Neonatal pCPA-treatment increased playing, social and locomotory behaviors assessed in adolescent rats of both sexes. The pCPA-treated rats demonstrated decreased Crh (17 days) and increased Trh (35 days) expression in the hypothalamic paraventricular nucleus (PVN). There was sex dimorphism in Htr2c (17 days) and VGF (35 days) in the prefrontal cortex, with the females expressing higher levels of it than males. Our results indicate that neonatal pCPA-treatment results in a long-lasting and sex-dependent DRN 5-HT synthesis changes, decreased Crh, and increased Trh expression in the PVN, resulting in a hyperactivity-like phenotype during adolescence. The present work demonstrates that the impairment of TPH function leads to neurobehavioral disorders related to hyperactivity and impulsivity, such as attention deficit hyperactivity disorder (ADHD)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The dorsal raphe nucleus (DRN) is essential for the control of food intake. Efferent projections from the DRN extend to several forebrain regions that are involved in the control of food intake. However, the neurotransmitters released in the DRN related to the control of food intake are not known. We have previously demonstrated that a tonic α1 action on DRN neurons contributes to satiety in the fed rats. In this study we investigated the participation of norepinephrine (NE) signaling in the DRN in the satiety response. Intra-DRN administration of NE causes an increase in the 2-hour food intake of sated mice, an effect that was blocked by previous administration of yohimbine, an α2 antagonist. Similarly, Intra-DRN administration of clonidine, an α2 agonist, increases food intake in sated mice. This result indicates that in the satiated mice exogenous NE acts on α2 receptors to increase food intake. Furthermore, administration of phenylephrine, an α1 agonist, decreases food intake in fasted mice and prazosin, an α1 antagonist, increases food intake in the sated mice. Taken together these results indicate that, in a satiated condition, a tonic α1 adrenergic action on the DRN neurons inhibits food intake and that exogenous NE administered to the DRN acts on α2 adrenergic receptors to increase food intake. These data reinforce the intricate neuronal functioning of the DRN and its effects on feeding., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: We hypothesized that perinatal manipulations of the nitrergic system would affect adult animal behaviors., Methods: We tested this hypothesis by perinatally administering N(G)-Nitro-L-arginine methyl ester (L-NAME), a non-specific antagonist of nitric oxide synthase for 15 days and assessed anxiety- and depression-like behaviors in adult mice. At 70 days of age, the mice were subjected to a battery of tests consisting of the open-field, light/dark box, forced swim, and tail-flick tests. The tests were performed at two-day intervals, and the order of the tests within the battery was determined according to the progressive invasiveness degree., Results: L-NAME-treated animals exhibited decreased anxiety-like behavior in the light/dark box and open field tests, with no change in locomotor activity. Additionally, they demonstrated decreased depression-like behavior in the forced swim test and no change in pain perception in the tail-flick test., Conclusion: The nitrergic system is possibly involved in neural circuitry development that regulates behaviors since blocking perinatal nitric oxide production decreases anxiety- and depression-like behaviors in adult mice.

Chronic alcohol exposure leads to a neuroinflammatory response involving activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and proinflammatory cytokine production. Acute ethanol (EtOH) exposure activates GABAergic synapses in the central and basolateral amygdala (BLA) ex vivo , but whether this rapid modulation of synaptic inhibition is because of an acute inflammatory response and alters anxiety-like behavior in male and female animals is not known. Here, we tested the hypotheses that acute EtOH facilitates inhibitory synaptic transmission in the BLA by activating the NLRP3 inflammasome-dependent acute inflammatory response, that the alcohol-induced increase in inhibition is cell type and sex dependent, and that acute EtOH in the BLA reduces anxiety-like behavior. Acute EtOH application at a binge-like concentration (22-44 mm) stimulated synaptic GABA release from putative parvalbumin (PV) interneurons onto BLA principal neurons in ex vivo brain slices from male, but not female, rats. The EtOH facilitation of synaptic inhibition was blocked by antagonists of the Toll-like receptor 4 (TLR4), the NLRP3 inflammasome, and interleukin-1 receptors, suggesting it was mediated by a rapid local neuroinflammatory response in the BLA. In vivo , bilateral injection of EtOH directly into the BLA produced an acute concentration-dependent reduction in anxiety-like behavior in male but not female rats. These findings demonstrate that acute EtOH in the BLA regulates anxiety-like behavior in a sex-dependent manner and suggest that this effect is associated with presynaptic facilitation of parvalbumin-expressing interneuron inputs to BLA principal neurons via a local NLRP3 inflammasome-dependent neuroimmune response. SIGNIFICANCE STATEMENT Chronic alcohol exposure produces a neuroinflammatory response, which contributes to alcohol-associated pathologies. Acute alcohol administration increases inhibitory synaptic signaling in the brain, but the mechanism for the rapid alcohol facilitation of inhibitory circuits is unknown. We found that acute ethanol at binge-like concentrations in the basolateral amygdala (BLA) facilitates GABA release from parvalbumin-expressing (PV) interneuron synapses onto principal neurons in ex vivo brain slices from male rats and that intra-BLA ethanol reduces anxiety-like behavior in vivo in male rats, but not female rats. The ethanol (EtOH) facilitation of inhibition in the BLA is mediated by Toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and proinflammatory IL-1β signaling, which suggests a rapid NLRP3 inflammasome-dependent neuroimmune cascade that plays a critical role in acute alcohol intoxication., (Copyright © 2023 the authors.)

Salinity is harmful to crops when the concentration of soluble salts overcomes the salinity threshold of the crop, causing osmotic stress and limitations in plant growth. In this scenario, adopting tolerant cultivars is the most adequate strategy to minimize agricultural losses. However, the inheritance of tolerance depends on the genotype. From this perspective, this study assessed the tolerance to severe salt stress in 11 cotton cultivars based on gas exchange parameters and the free proline content. The cultivars were grown in a greenhouse and subjected to 34 days of saline irrigation (10 dS m-1), starting 45 days after seedling emergence (B1 phase). Plant growth was monitored weekly until the end of the salt stress period. The treatments consisted of a combination of two factors: eleven cultivars associated with two electrical conductivity levels of irrigation water (ECw: 0.3 and 10.0 dS m-1). The experimental design was in randomized blocks in a 11 × 2 factorial arrangement with three replications (66 plots), with the experimental unit consisting of one plant per plot. Salinity impacted plant growth, being reflected on the gas exchange and free proline data of most cultivars. However, BRS 286, FMT 705, BRS 416, and BRS Acácia, and CNPA 7MH withstood the effects of stress and osmotically adjusted to the salt stress conditions, thus minimizing the damage to growth. Those cultivars are the most indicated for improvement programs aiming at tolerance to salt stress based on the results found in this research.

Stress induces changes in nervous system function on different signaling levels, from molecular signaling to synaptic transmission to neural circuits to behavior-and on different time scales, from rapid onset and transient to delayed and long-lasting. The principal effectors of stress plasticity are glucocorticoids, steroid hormones that act with a broad range of signaling competency due to the expression of multiple nuclear and membrane receptor subtypes in virtually every tissue of the organism. Glucocorticoid and mineralocorticoid receptors are localized to each of the cellular compartments of the receptor-expressing cells-the membrane, cytosol, and nucleus. In this review, we cover the neuroendocrine effects of stress, focusing mainly on the rapid actions of acute stress-induced glucocorticoids that effect changes in synaptic transmission and neuronal excitability by modulating synaptic and intrinsic neuronal properties via activation of presumed membrane glucocorticoid and mineralocorticoid receptors. We describe the synaptic plasticity that occurs in 4 stress-associated brain structures, the hypothalamus, hippocampus, amygdala, and prefrontal cortex, in response to single or short-term stress exposure. The rapid transformative impact of glucocorticoids makes this stress signal a particularly potent effector of acute neuronal plasticity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Vasopressin (AVP) and oxytocin (OXT) are neuropeptides produced by magnocellular neurons (MCNs) of the hypothalamus and secreted through neurohypophysis to defend mammals against dehydration. It was recently demonstrated that MCNs also project to limbic structures, modulating several behavioral responses., Methods and Results: We found that 24 h of water deprivation (WD) or salt loading (SL) did not change exploration or anxiety-like behaviors in the elevated plus maze (EPM) test. However, rats deprived of water for 48 h showed reduced exploration of open field and the closed arms of EPM, indicating hypoactivity during night time. We evaluated mRNA expression of glutamate decarboxylase 1 (Gad1), vesicular glutamate transporter 2 (Slc17a6), AVP (Avpr1a) and OXT (Oxtr) receptors in the lateral habenula (LHb), basolateral (BLA) and central (CeA) amygdala after 48 h of WD or SL. WD, but not SL, increased Oxtr mRNA expression in the CeA. Bilateral pharmacological inhibition of OXTR function in the CeA with the OXTR antagonist L-371,257 was performed to evaluate its possible role in regulating the EPM exploration or water intake induced by WD. The blockade of OXTR in the CeA did not reverse the hypoactivity response in the EPM, nor did it change water intake induced in 48-h water-deprived rats., Discussion: We found that WD modulates exploratory activity in rats, but this response is not mediated by oxytocin receptor signaling to the CeA, despite the upregulated Oxtr mRNA expression in that structure after WD for 48 h., 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 © 2023 Felintro, Trujillo, dos-Santos, da Silva-Almeida, Reis, Rocha and Mecawi.)

Social media have expanded the exposure of vegan consumption decisions and practices through the greater reach of opinions issued digitally by individuals concerned about ethical and environmental issues. Some of these people have reached considerable numbers of followers virtually, becoming digital influencers with built-in credibility that makes them opinion leaders. Considering them, this study aims to analyze the relationship between source credibility and the social media use in the purchase intention of vegan products endorsed by digital influencers, focusing on the cosmetics industry. We used the cross-sectional survey method and adopted Structural Equation Modeling to analyze the relationships between the variables from 190 valid questionnaires. We identified that both the social media use and the source credibility influence the purchase intention of vegan cosmetic products. The ability of digital influencers to shape consumer intentions was recognized, even though the products they endorse do not represent the follower's philosophy of life-for example, a nonvegan follower who intends to consume a vegan cosmetic from the digital influencer endorsement. Furthermore, we identified that the source credibility influences the social media use that is the influencer also shapes the individual digital behavior., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

New Findings: What is the central question of this study? What is the effect of an obesogenic diet on the control of hydromineral balance in rats? What is the main finding and its importance? The results showed that, when dehydrated, rats fed a high-fat diet drink less water than their control-diet-fed counterparts. Changes in aquaporin-7 and peroxisome proliferator-activated receptor α expression in the white adipose tissue might be involved., Abstract: High-fat diet (HFD) increases fat accumulation, glycaemia and blood triglycerides and is used as a model to study obesity. Besides the metabolic changes, obesity likely affects water intake. We assessed the effects of HFD on behavioural and hormonal responses to water deprivation. Additionally, we measured if the adipose tissue is differentially affected by water deprivation in control and HFD-fed rats. HFD rats showed a decreased basal water intake when compared to control-fed rats. When subjected to 48 h of water deprivation, as expected, both control and HFD rats drank more water than the hydrated rats. However, the increase in water intake was lessened in HFD dehydrated rats. Similarly, the increase in haematocrit in dehydrated rats was less pronounced in HFD dehydrated rats. These results suggest that HFD diminishes drinking behaviour. White adipose tissue weight, glycaemia and plasma glycerol concentration were increased in HFD rats; however, after 48 h of water deprivation, these parameters were significantly decreased in dehydrated HFD rats, when compared to controls. The increase in adipose tissue caused by HFD may mitigate the effects of dehydration, possibly through the increased production of metabolic water caused by lipolysis in the adipocytes. Oxytocin possibly mediates the lipolytic response, since both its secretion and receptor expression are affected by dehydration in both control and HFD rats, which suggests that oxytocin signalling is maintained in these conditions. Changes in mediators of lipolysis, such as aquaporin-7 and peroxisome proliferator-activated receptor α, might contribute to the different effects observed in control and HFD rats., (© 2022 The Authors. Experimental Physiology © 2022 The Physiological Society.)

Serotonin exerts a significant role in the mammalian central nervous system embryogenesis and brain ontogeny. Therefore, we investigate the effect of neonatal treatment of d-fenfluramine (d-FEN), a serotonin (5-HT) releaser, on the behavioral expression of adult male Swiss mice. For this purpose, we divided pregnant female Swiss mice into two groups (n = 6 each and ~35 g). Their offspring were treated with d-FEN (3 mg/kg, s.c.) from postnatal days (PND) 5 to 20. At PND 21, one male puppy of each litter was euthanized; the midbrain and the hippocampus were dissected for RNA analysis. At PND 70, the male offspring underwent a behavioral assessment in the open field, elevated plus-maze, light-dark box, tail suspension, and rotarod test. The programmed animals had a decrease in 5HT1a, serotonin transporter (SERT), and brain-derived neurotrophic factor (BDNF) expression in the mesencephalic raphe region. Alternatively, there was a reduction only in the tryptophan hydroxylase (TPH2) and BDNF expression in the hippocampus. In the light-dark box test, offspring of the treated group had higher latency to light and less time on the light side than the control. Also, it was observed less time of immobility in the tail suspension test. We also observed low motor skill learning in the rotarod test. These findings suggest that programming with d-FEN during the neonatal period alters a mesencephalic and hippocampal serotonergic system, promoting anxiety, antidepressant behavior, low coordination, and motor learning in adults., (© 2022 International Society for Developmental Neuroscience.)

Peanut (Arachis hypogaea L.) is an important crop for the family-based systems in the tropics, mainly in Brazil. In the Brazilian drylands, peanuts are cropped in low technological systems, and cheap and efficient technologies are needed to improve crop yield and sustainability. Despite this importance, few data are available on selecting efficient peanut rhizobia in experiments under different edaphoclimatic conditions. This work evaluated the agronomic efficiency and the biological nitrogen fixation (BNF) by two elite Bradyrhizobium strains under four different fields in the Brazilian semiarid region. We compared a new efficient strain Bradyrhizobium sp. ESA 123 with the reference strain B. elkanii SEMIA 6144, currently used in peanut rhizobial inoculants in Brazil. Besides the inoculated treatments, two uninoculated controls were assessed (with and without 80 kg ha -1 of N-urea). The BNF was estimated by the δ 15 N approach in three out of four field assays. BNF contribution was improved by inoculation of both Bradyrhizobium strains, ranging from 42 to 51% in Petrolina and 43 to 60% in Nossa Senhora da Glória. Peanuts' yields benefited from the inoculation of both strains and N fertilization in all four assays. Nevertheless, the results showed the efficiency of both strains under different edaphoclimatic conditions, indicating the native strain ESA 123 as a potential bacterium for recommendation as inoculants for peanuts in Brazil, mainly in drylands., (© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Building occlusions usually decreases the accuracy of boundary regularization. Thus, it is essential that modeling methods address this problem, aiming to minimize its effects. In this context, we propose a weighted iterative changeable degree spline (WICDS) approach. The idea is to use a weight function for initial building boundary points, assigning a lower weight to the points in the occlusion region. As a contribution, the proposed method allows the minimization of errors caused by the occlusions, resulting in a more accurate contour modeling. The conducted experiments are performed using both simulated and real data. In general, the results indicate the potential of the WICDS approach to model a building boundary with occlusions, including curved boundary segments. In terms of F score and PoLiS , the proposed approach presents values around 99% and 0.19 m, respectively. Compared with the previous iterative changeable degree spline (ICDS), the WICDS resulted in an improvement of around 6.5% for completeness, 4% for F score , and 0.24 m for the PoLiS metric.

Anacardic acid is naturally found in various parts of the cashew tree (Anacardium occidentale L.) and marketed as calcium anacardate. This product has antibacterial, antifungal and antioxidant activity, and has been used in humans in the treatment and prevention of cardiovascular and cerebrovascular diseases and tumors. In meat and egg production systems, anacardic acid is used as a substitute for growth-promoting antibiotics. The study objective was to evaluate effects of adding calcium anacardate as source of anacardic acid in laying Japanese quail diet on bird performance and eggs quality. A total of 252 Japanese quail with 22 week-old were studied, using a completely randomized design composed of six treatments with six replicates and seven quails per experimental unit. Treatments applied were: diet without growth promoter; diet with 0,1% growth promoter; and four diets without growth promoter and addition of 0.25; 0.50; 0.75 and 1.0% calcium anacardate (CA), respectively. The data were submitted to analysis of variance and treatment means compared with a SNK test (5%). The data from treatments containing CA were submitted to regression analysis. Treatments did not influence feed intake, egg production, egg weight, egg volume, feed conversion ratio and eggs quality parameters. The addition up to 1% of calcium anacardate in laying Japanese quail diet, does not influence their performance and egg quality.

Hypovolemia induced by hemorrhage is a common clinical complication, which stimulates vasopressin (AVP) secretion by the neurohypophysis in order to retain body water and maintain blood pressure. To evaluate the role of brain L-glutamate and angiotensin II on AVP secretion induced by hypovolemia we induced hemorrhage (∼25% of blood volume) after intracerebroventricular (icv) administration of AP5, NBQX, or losartan, which are NMDA, AMPA, and AT1 receptor antagonists, respectively. Hemorrhage significantly increased plasma AVP levels in all groups. The icv injection of AP5 did not change AVP secretion in response to hemorrhage. Conversely, icv administration of both NBQX and losartan significantly decreased plasma AVP levels after hemorrhage. Therefore, the blockade of AMPA and AT1 receptors impaired AVP secretion in response to hemorrhage, suggesting that L-glutamate and angiotensin II acted in these receptors to increase AVP secretion in response to hemorrhage-induced hypovolemia.

Background: Appropriate substituents in the galloyl group could lead to significant biological properties., Objectives: Novel galloyl-substituted compounds bearing 2-substituted-1, 3, 4-oxadiazol-5-yl, 5- substituted-1,2,4-triazol-3-yl, and carboxamide groups were synthesized and evaluated for their antiproliferative activity. Additionally, galloyl hydrazide (2) was evaluated by performing cytotoxicity, membrane integrity, cell cycle, and apoptosis assays in HepG2/C3A cells., Methods: General procedure was used for the synthesis of galloyl-substituted (3-9, 11) and characterized by their spectroscopic data (1H and 13C NMR). The antiproliferative activity of all novel galloyl derivatives was evaluated against nine human tumors and one nontumoral cell line. Three response parameters (GI50, TGI, and LC50) were calculated. The cytotoxicity test was performed for the resazurin assay. The membrane integrity, cell cycle, and apoptosis assays were performed by flow cytometry., Results: The substitution of the methoxy group of the galloyl ring system for a carboxamide group (3, 4, 5, and 6) produced compounds with moderate antitumoral activity, particularly 6, against six human cancer cell lines, K-562, PC-3, NCI-ADR/RES, OVCAR, 786-0 and NCI-H460, with GI50 values ≤ 9.45 μg/mL. Triazole derivatives 7 and 8 exhibited higher antitumoral activity toward OVCAR, MCF-7 and leukemia K-562 cell lines, exhibiting GI50 values less than 10 μg/mL. Compound 11 displayed significant activity against PC-3 (GI50 = 4.31 μg/mL), OVCAR (GI50 = 8.84 μg/mL) and K-562 (GI50 = 8.80 μg/mL) cell lines. Galloyl hydrazide (2) had cytotoxic activity in HepG2/C3A cells (IC50 = 153.7 μg/mL). In membrane permeability, cell count, cell cycle, and apoptosis assays, as determined using the IC50 of compound (2) in HepG2/C3A cells, increased membrane permeability, decreased cell count, altered cell cycle, and initial apoptosis was observed compared to the control group., Conclusion: Thus, our results showed for the first time the synthesis, antiproliferative activity, and cytotoxicity of galloyl-substituted compounds. Galloyl-substitution does not have a very strong synergistic effect in the inhibition of cancer cell proliferation compared with galloyl hydrazide (2). Compound 2 demonstrated promising activity in HepG2/C3A hepatocarcinoma cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Tyrosine kinase inhibitors (TKIs) are antitumor compounds that prevent the phosphorylation of proteins in a biological environment. However, the multitarget performance of TKIs promotes them as possible candidates for drug repositioning. In this work, interaction and inhibition studies through spectroscopic and computational techniques to evaluate the binding effectiveness of lapatinib and pazopanib TKIs to acetylcholinesterase (AChE) are reported. The results indicated potent inhibition at the μM level. The types of inhibition were identified, with pazopanib acting through non-competitive inhibition and lapatinib through acompetitive inhibition. The fluorescence suppression studies indicate a static mechanism for lapatinib-AChE and pazopanib-AChE systems, with a binding constant in the order of 10 5 M -1 . The obtained thermodynamic parameters reveal interactions driven by van der Waals forces and hydrogen bonds in the lapatinib-AChE system (Δ H ° and Δ S ° < 0). In contrast, the pazopanib-AChE system shows positive Δ H ° and Δ S °, characteristic of hydrophobic interactions. The Foster resonance energy transfer study supports the fluorescence studies performed. The 3D fluorescence studies suggest changes in the microenvironment of the tryptophan and tyrosine residues of the protein in contact with lapatinib and pazopanib. The results suggest effective inhibition and moderate interaction of the drugs with AChE, making them interesting for conducting more in-depth repositioning studies as AChE inhibitors.

The beneficial features of Bacillus thuringiensis (Bt) are not limited to its role as an insecticide; it is also able to promote plant growth interacting with plants and other plant growth-promoting rhizobacterium (PGPR). The PGPR Bt strain RZ2MS9 is a multi-trait maize growth promoter. We obtained a stable mutant of RZ2MS9 labelled with green fluorescent protein (RZ2MS9-GFP). We demonstrated that the Bt RZ2MS9-GFP successfully colonizes maize's roots and leaves endophytically. We evaluated whether RZ2MS9 has an additive effect on plant growth promotion when co-inoculated with Azospirillum brasilense Ab-V5. The two strains combined enhanced maize's roots and shoots dry weight around 50% and 80%, respectively, when compared to the non-inoculated control. However, non-differences were observed comparing RZ2MS9 alone and when co-inoculated with Ab-V5, In addition, we used co-inoculation experiments in glass chambers to analyse the plant's volatile organic compounds (VOCs) production during the maize-RZ2MS9 and maize-RZ2MS9-Ab-V5 interaction. We found that the single and co-inoculation altered maize's VOCs emission profile, with an increase in the production of indoles in the co-inoculation. Collectively, these results increase our knowledge about the interaction between the Bt and maize, and provide a new possibility of combined application with the commercial inoculant A. brasilense Ab-V5., (© 2021 Society for Applied Microbiology and John Wiley & Sons Ltd.)

The dorsal raphe (DR) nucleus is involved in a myriad of physiological functions, such as the control of sleep-wake cycle, motivation, pain, energy balance, and food intake. We have previously demonstrated that in ad libitum fed rats the intra-DR administration of phenylephrine, an α-1 receptor agonist, does not affect food intake, whereas clonidine, an α-2 receptor agonist, potently stimulates food intake. These results indicated that in fed rats an increased adrenergic tonus blocked food intake, since the activation of α-2 auto-receptors, which decreases pre-synaptic release of adrenaline/noradrenaline, affected food intake. Thus, in this study we assessed whether the response to adrenergic stimuli would differ after overnight fasting, a situation of low adrenergic activity in the DR. Intra-DR administration of adrenaline and noradrenaline blocked food intake evoked by overnight fasting. Similarly, phenylephrine administration decreased hunger-induced food intake. These changes in food intake were accompanied by changes in other behaviors, such as increased immobility time and feeding duration. On the other hand, intra-DR administration of clonidine did not affect food-intake or associated behaviors. These results further support the hypothesis that in fed animals, increased adrenergic tonus in DR neurons inhibiting feeding, while in fasted rats the adrenergic tonus decreases and favors food intake. These data indicate a possible mechanism through which adrenergic input to the DRN contributes to neurobiology of feeding., 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 © 2021 Flores, Dos-Santos, Steinbach, Rodrigues-Santos, de Jesus, Antunes-Rodrigues and Paschoalini.)

The Brazilian strategy to overcome the spread of COVID-19 has been particularly criticized due to the lack of a national coordinating effort and an appropriate testing program. Here, a successful approach to control the spread of COVID-19 transmission is described by the engagement of public (university and governance) and private sectors (hospitals and oil companies) in Macaé, state of Rio de Janeiro, Brazil, a city known as the National Oil Capital. In 2020 between the 17th and 38th epidemiological week, over two percent of the 206,728 citizens were subjected to symptom analysis and RT-qPCR testing by the Federal University of Rio de Janeiro, with positive individuals being notified up to 48 h after swab collection. Geocodification and spatial cluster analysis were used to limit COVID-19 spreading in Macaé. Within the first semester after the outbreak of COVID-19 in Brazil, Macaé recorded 1.8% of fatalities associated with COVID-19 up to the 38th epidemiological week, which was at least five times lower than the state capital (10.6%). Overall, considering the successful experience of this joint effort of private and public engagement in Macaé, our data suggest that the development of a similar strategy countrywise could have contributed to a better control of the COVID-19 spread in Brazil. Quarantine decree by the local administration, comprehensive molecular testing coupled to scientific analysis of COVID-19 spreading, prevented the catastrophic consequences of the pandemic as seen in other populous cities within the state of Rio de Janeiro and elsewhere in Brazil., (© 2021. The Author(s).)

Peptic ulcer episodes cause damage to the stomach and intestine, with inflammatory cell infiltration and oxidative stress as the main players. In this study, we investigated the potential of anthocyanidin malvidin for preventive and curative peptic ulcer treatment. The anthocyanidin effects were examined in gastric ulcer mouse models induced by ethanol, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion (IR), acetic acid and duodenal ulcer induced by polypharmacy. Expression levels of oxidative and inflammatory genes were measured to investigate the mechanism of anthocyanin activity. At a dose of 5 mg·kg -1 , Malvidin prevented gastric ulcer induction by ethanol, NSAID and repaired the tissue after 6 days of IR. Moreover, the anthocyanidin accelerated the healing of acetic acid-induced ulcer, increased the gene expression of EGF and COX-1, and downregulated MMP-9. Anthocyanin treatment mitigated the effect of polypharmacy on inflammation and oxidative stress observed in the intestine. Additionally, the compound downregulated cytokine expression and TLR4 and upregulated HMOX-1 and IL-10, exhibiting protective activity in the mouse gut. Malvidin thus prevented gastric and duodenal ulcers due to prominent anti-inflammatory and antioxidative effects on the gastrointestinal tract that were related to gene expression modulation and an increase in endogenous defense mechanisms.

Objective: To analyze the risk of violence associated to functional capacity and sociodemographic characteristics of hospitalized elderly., Method: Quantitative, cross-sectional, multicenter study conducted with elderly receiving care at university hospitals of the municipalities of João Pessoa and Campina Grande, in the state of Paraíba, Brazil. The scales Katz and Hwalek-Sengstock Elder Abuse Screening Test were applied. The data was analyzed through descriptive and inferential statistics using Chi-squared Pearson test, Spearman correlation test, and multiple logistic regression., Results: The participating elderly amounted to 323. The risk of violence was predominant among female elders aged 60 to 70 who are unable to read or write, live with someone, perform no labor activity, and whose income is higher than a minimum wage. Elders who were dependent for basic and instrumental activities presented a 2.11 score (Confidence Interval = 1.22-3.64; p = 0.000) and 1.70 (1.01-2.85; p = 0.044) and a higher risk of violence., Conclusion: Elders who depended on other people to perform both complex and basic activities are the most exposed to situations of violence.

The serotoninergic system plays an important role in the ontogeny of the mammalian central nervous system, and changes in serotonin production during development may lead to permanent changes in brain cytoarchitecture and function. The present study investigated the programming effects of neonatal serotonin depletion on behavior and molecular components of the serotoninergic system in adult male and female rats. Subcutaneous para-chlorophenylalanine (pCPA) administration (100 mg kg -1 ) was performed daily on postnatal days 8-16 to deplete brain serotonin content. During adulthood, elevated plus-maze, open field, social interaction, forced swimming, and food, saline, and sucrose intake tests were performed. Relative expression of serotonin neurotransmission components in several brain areas was determined by qPCR. Additionally, serotonin immunofluorescence and neuropeptide mRNA expression were assessed in dorsal raphe (DRN) and paraventricular (PVN) nuclei, respectively. Rat performance in behavioral tests demonstrated a general increase in locomotor activity and active escape behavior as well as decreased anxiety-like behavior after neonatal brain serotonin depletion. The behavioral programming effects due to neonatal serotonin depletion were more pronounced in females than males. At the gene expression level, the mRNA of Tph1 and Tph2 were lower in DRN while Htr2c was higher in the amygdala of pCPA-treated males, while Htr1a, Htr2c, Oxt, Avp, Crh, and Trh were not different in any treatments or sex in PVN. The results indicate that neonatal serotonin depletion has long-term consequences on locomotion and anxiety-like behavior associated with long-lasting molecular changes in the brain serotoninergic system in adult rats.

Serotonin exerts a significant role in the mammalian central nervous system embryogenesis and brain ontogeny. Therefore, we investigate the effect of perinatal fluoxetine (FLX), a selective serotonin reuptake inhibitor, administration on the behavioral expression of adult male Swiss mice. For this purpose, two groups (n = 6 each, and ~ 35 g) of pregnant female Swiss mice were mated. Their offspring were treated with FLX (10 mg/Kg, s.c.) from postnatal day (PND) 5 to 15. At PND 16, one male puppy of each litter was euthanized, and the hippocampus was dissected for RNA analysis. At 70 days of life, the male offspring underwent a behavioral assessment in the open field, object recognition task, light-dark box, tail suspension and rotarod test. According to our results, the programmed animals had a decrease in TPH2, 5HT1a, SERT, BDNF, and LMX1B expression. Also, it was observed less time of immobility in tail suspension test and higher grooming time in the open field test. In the light-dark box test, the FLX-treated offspring had less time in the light side than control. We also observed a low cognitive performance in the object recognition task and poor motor skill learning in the rotarod test. These findings suggest that programming with FLX during the neonatal period alters a hippocampal serotonergic system, promoting anxiety and antidepressant behavior in adults, as well as a low mnemonic capacity.

Aim: The present study investigated the effects of anabolic steroid (AS) excess on blood pressure regulation., Methods: Male Wistar rats were treated with nandrolone decanoate (AS) or vehicle (CTL) for 8 or 10 weeks. Saline (1.8%) and water intake were measured in metabolic cages. Urinary volume, osmolarity, Na + and K + concentrations, and plasma osmolarity were measured. The autonomic balance was estimated by heart rate variability at baseline or after icv injection of losartan. Cardiac function was assessed by echocardiography and ex vivo recordings. Myocardial collagen deposition was evaluated by Picrosirius-Red staining. Vascular reactivity and wall thickness were investigated in aortic sections. Blood pressure (BP) was assessed by tail-cuff plethysmography. Angiotensin II type I receptor (AT1R), renin, and mineralocorticoid receptor (MR) mRNA expression was measured in the kidneys and whole hypothalamus., Results: AS group exhibited decreased urinary volume and Na + concentration, while urinary K + concentration, plasma osmolarity, and renal AT1R and renin mRNA levels were increased compared to CTL (p < 0.05). Water intake was increased, and saline intake was decreased in the AS group (p < 0.01). AS group exhibited increased low-frequency/high-frequency-ratio, while it was decreased by icv injection of losartan (p < 0.05) compared to baseline. Neither cardiac function nor vascular reactivity/morphology was affected by AS excess (p > 0.05). Ultimately, BP levels were not altered by AS excess (p > 0.05)., Conclusion: AS excess promoted hydroelectrolytic and autonomic imbalance but did not alter vascular or cardiac function/morphology., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to analyze the association between frailty syndrome as a risk factor associated with violence in older adults., Method: A cross-sectional study, carried out with older adults, in an emergency care unit of a northeastern Brazilian city was conducted. Three instruments were used: a form for sample characterization (i.e., demographics) and two more scales, namely, the Edmonton Frail Scale and the Hwalek-Sengstock Elder Abuse Screening Test. The results were analyzed through descriptive and inferential statistics, using chi-square or Fisher's exact tests, Spearman's correlation test, and simple logistic regression., Results: The sample included 146 older adults who were over 70 years old (56.6%), male (56.2%), and at risk of violence (69.86%). Among the categorical variables, there was an association between risk and being of a higher age (80.7%, p < 0.001), unemployed (73.7%, p < 0.05), having more than six children (80.8%, p < 0.05), and frail older adults (88.1%, p < 0.001). There was a correlation (p < 0.05) between the numerical variables of the scales of violence and frailty, with a coefficient of 0.40. The simple logistic regression model showed that frailty syndrome increases the risk of violence among older adults., Conclusions: It was concluded that frailty is a factor that increases the occurrence of risk of violence and provides information to guide nursing action in the field of forensic sciences.

Bidens gardneri Baker, popularly known as "picão-vermelho", has been used, traditionally, as a medicinal plant for the treatment of Diabetes mellitus. This study aimed to evaluate antidiabetic effect of leaves from B. gardneri aqueous extract (BGAE). We also evaluated in vitro anti-glycation potential. Chemical composition was analyzed based on a colorimetrics and HPLC methods. The oral glucose tolerance test (OGTT), was performed in rats with different doses (30, 100 and 300 mg/kg). Alloxan-induced diabetic and hypercaloric diet-fed rats were treated with 300 mg/kg of BGAE, orally, for 10 days and then 10 weeks, respectively. The activity of intestinal disaccharidases (maltase, sucrase and lactase) and quantification of muscle and liver glycogen content were also evaluated. On chemical analysis, the extract showed high phenolics content and the chromatogram showed 4-O-caffeoylquinic acid as the major component. The extract presented inhibition in the formation of advanced glycation end products (AGEs) and disaccharidases activity. In OGTT the dose of 300 mg/kg significantly decreased the blood glucose. In diabetic animals, BGAE significantly decreased blood glucose levels, preventing weight loss. In addition, in hypercaloric diet-fed rats, the extract prevented hyperglycemia. Our results suggest that, aqueous extract of B. gardneri has a potential for therapeutic intervention of diabetes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing interest., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: The extensively drug-resistant (XDR) Acinetobacter baumannii international clone VI (IC-6) has been identified worldwide since 2006. This study reports the emergence of IC-6 in the Brazilian Amazon region and reveals the particular genomic features considering its mobilome and resistome., Methods: A total of 32 carbapenem-resistant A. baumannii strains recovered from Boa Vista city (Roraima, Brazil) in 2016 were characterised by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The whole genome sequences of the Brazilian IC-6 strains were obtained. The mobilome and resistome were assessed by in silico analyses., Results: PFGE and MLST demonstrated that the 32 A. baumannii strains belonged to four clones. One XDR clone corresponded to the high-risk pandemic IC-6 lineage from ST944 Oxf /78 Pas . The IC-6 resistome was composed of aadA5, aac(3'')-IIa, aph(3')-Ia, armA, aadB, msrE, bla TEM-1 , IS15DIV-bla CTX-M-115 -IS15DIV, bla OXA-90 , ISAba1-bla ADC-152 , bla OXA-72 , qacEΔ1 and sul1. Mobilome prediction revealed that bla OXA-72 was embedded in a 15.5-kb plasmid and that it was flanked by putative XerC/D-binding sites, possibly involved in bla OXA-72 mobilisation. Several resistance genes were in a 48-kb multidrug resistance genomic island inserted in the chromosome, which also harboured genes involved in host pathogenicity and adaptive traits. Interestingly, the Brazilian strains shared the bla OXA-72 and bla CTX-M-115 with IC-6/ST944 Oxf /78 Pas recovered in a distinct spatiotemporal context, pointing to an epidemiological link among them., Conclusion: This study highlights the importance of surveillance of XDR A. baumannii strains, even outside of densely populated cosmopolitan regions, to reveal the epidemiology of pandemic lineages, stressing their threat to public health., (Copyright © 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.)

Visceral leishmaniasis (VL) is a neglected tropical disease, caused by Leishmania (Kinetoplastida, Trypanosomatidae) species. In Brazil, the transmission of this parasite essentially occurs through the bite of Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae) previously infected with Leishmania infantum. Aiming at preventing VL expansion over the country, integrated control actions have been implemented through a Visceral Leishmaniasis Surveillance and Control Program (VLSCP). Among the actions currently adopted by the program, the screening-culling of seropositive dogs for canine VL (CVL) is particularly polemic. Dogs with negative or divergent serology for CVL remain in their owner's domicile and are monitored by public health agents. In the present study, we determined the prevalence of CVL and analyzed the implementation of the VLSCP screening-culling action, in an area in Brazil where there has been a recent expansion of VL. Canine census surveys were conducted semiannually for two years (Aug/2015 to Feb/2017). Serological diagnosis of CVL was performed in accordance with current VLSCP protocol: immunochromatography (TR-DPP) followed by enzyme-linked immunosorbent assay (ELISA EIE). 6,667 dogs were serologically screened for CVL, of which 567 (8.5%) were positive in both tests and 641 (9.6%) had divergent results. A variable percentage (6.3% to 65.4%) of the dogs in the latter group became positive within nine months from the first result. Xenodiagnosis was conducted in canine samples belonging to any of the three possible serological statuses for CVL-positive, divergent or negative. Leishmania spp. DNA was detected in Lu. longipalpis that fed on 50.0% (5/10) of dogs with positive serology and on 29.4% (5/17) of dogs with divergent serological status for CVL. Therefore, dogs with divergent serology for CVL may be as Leishmania-infective to Lu. longipalpis as seropositive ones. Even with the adoption of euthanasia for seropositive dogs, part of the canine population will continue to serve as a source of Leishmania infection for phlebotomine sand flies., Competing Interests: The authors have declared that no competing interests exist.

Chrysin exhibits anti-inflammatory and antioxidant activities. Here, the gastroprotective effect of chrysin was investigated in mouse models of gastric ulcer induced by absolute ethanol, acetic acid, and ischemia-reperfusion injury. The gastric-healing effect was evaluated at 7 and 14 days after treatment; the mechanism of action was verified using the expression of metalloproteinase 2 ( MMP-2 ) and 9 ( MMP-9 ), caspase-3, cyclooxygenase 1 ( COX-1 ) and 2 ( COX-2 ), epidermal growth factor ( EGF ), and interleukin-10. Chrysin (10 mg/kg) inhibited macroscopic lesions and increased catalase activity in the mouse model established using absolute ethanol. It ameliorated the gastric ulcer caused by acetic acid by improving the expression of inflammatory genes such as COX-2 , inhibiting negative remodeling promoted by MMP-9, increasing cell proliferation effect via EGF , and reducing cellular apoptosis by modulating caspase-3. A faster healing effect was evident in the first 7 days of treatment compared to 14 days of treatment, indicating the pharmacological potential of chrysin. Overall, these results demonstrate the potent effect of chrysin in the gastrointestinal tract and elucidate the genes involved in the healing of gastric ulcers. Moreover, an increase in the levels of gastric mucosa defensive factors is involved in the activity of chrysin in the gastric mucosa., Competing Interests: The authors declare that they have no conflicts of interest.Abbreviations:

Background: Diabetes mellitus is one of the most common todays public health problems. According to a survey by the World Health Organization, this metabolic disorder has reached global epidemic proportions, with a worldwide prevalence of 8.5% in the adult population., Objectives: The present study aimed to investigate the hypoglycemic effect of aqueous extract of Mangifera indica (EAMI) leaves in streptozotocin-induced diabetic rats., Methods: Sixty male rats were divided into 2 groups: Normoglycemic and Diabetic. Each group was subdivided into negative control, glibenclamide 3 or 10 mg/kg, EAMI 125, 250, 500, and 1000 mg/kg. Intraperitoneal injection of streptozotocin 100 mg/kg was used to DM induction. The hypoglycemic response was assessed acutely after two and four weeks of treatment. After a 6-hour fasting period, the fasting blood glucose of animals was verified, and 2.5 g/kg glucose solution was orally administered. The insulin tolerance test and plasma insulin levels assessment were performed in the morning after fasting of 12 to 14 hours., Results and Conclusion: The chemical analysis of EAMI showed high levels of phenolic compounds. There was no significant difference in fasting blood glucose between normoglycemic and diabetic groups, and that EAMI did not have an acute effect on diabetes. After two and four weeks of treatment, the extract significantly reduced blood glucose levels, exceeding glibenclamide effects. EAMI was effective in maintaining the long-term hypoglycemic effect, as well as, significantly increased the sensitivity of diabetic animals to insulin and the plasma insulin level., Competing Interests: The authors have declared that no competing interests exist.

Objective: To use ultrasound to investigate the morbidity related to schistosomiasis in the Xakriabá indigenous population., Materials and Methods: This was a field-based census study conducted in the territory of the Xakriabá people. A total of 166 individuals were invited, and 148 (≤ 77 years of age) agreed to participate. Most participants underwent abdominal ultrasound, physical examination, and stool examination. Mann-Whitney U and chi-square tests were used for comparisons. We determined risk by calculating odds ratio (OR) and performed logistic regression analysis., Results: Schistosoma mansoni eggs were found in 31 (26.7%) of the 116 stool samples examined, 22 (70.9%) of the 31 being from individuals 4-16 years of age. The median count was 144 eggs/g of feces (interquartile range, 264). Of the 105 participants examined with ultrasound, 68 (64.8%) had hepatomegaly (left lobe), 6 (5.7%) had splenomegaly, and 4 (3.8%) had portal hypertension. Egg-positive stool samples were more common in those with an enlarged left lobe (OR = 3.4; 95% confidence interval (CI): 1.1-11.2; p = 0.043). Periportal fibrosis was found in 30 participants (28.6%), of whom 9 (30%) had pattern C, 10 (33.3%) had pattern D, and 11 (36.7%) had pattern Dc. Age was the only independent risk factor for fibrosis ( p = 0.007). Fibrosis was up to nine-fold more common in alcohol drinkers than in nondrinkers (OR = 9.28; 95% CI: 2.60-33.06; p < 0.001). Among the 138 participants in whom the clinical form was classified, the chronic hepatic form was identified in 54 (39.1%), of whom 32 (59.2%) were under 30 years of age and one (1.8%) was hepatosplenic., Conclusion: Schistosomiasis in the Xakriabá population is characterized by a high frequency of egg-positive stool samples, predominantly in children/adolescents, and by chronic hepatic form in the young, especially among alcohol drinkers.

New Findings: What is the central question of this study? Can Na + depletion mobilize Na + from the skin reservoir in ovariectomized rats? Does oestrogen replacement change the amount and the dynamics of skin Na + storage? Is the reduced salt appetite after Na + depletion in ovariectomized rats with oestrogen replacement related to changes in the skin Na + ? What is the main finding and its importance? This work demonstrated that acute body Na + depletion induced by frusemide mobilized the osmotically inactive skin Na + reservoir to become osmotically active. Oestrogen treatment decreased the induced Na + intake in ovariectomized rats but did not modulate the inactive Na + reservoir in control conditions or its mobilization induced by Na + depletion., Abstract: Oestradiol, which is an important hormone for water and electrolyte balance, also has a role in the inhibition of induced Na + appetite. Sodium can be stored in the skin in osmotically active or inactive forms, and this skin Na + reservoir may be involved in the control of body Na + levels during physiopathological challenges. In this study, we investigated whether the effect of sodium depletion by frusemide can mobilize Na + from the skin reservoir and whether oestradiol replacement changes or mobilizes the Na + reserves in the skin. Ovariectomized Wistar rats were treated with vehicle or oestradiol for 7 days to evaluate the effects of oestrogen on the hydroelectrolyte balance, intake responses and skin Na + and water content in basal conditions. Furthermore, the effects of oestrogen were evaluated after 24 h frusemide-induced whole-body Na + depletion. Oestradiol-replaced rats exhibited reduced water intake without any significant changes in salt intake, Na + excretion or water and Na + skin content in basal conditions. After sodium depletion, both vehicle- and oestradiol-treated rats exhibited an increase in the osmotically active skin Na + , which was associated with a decrease of the inactive skin Na + reservoir. Oestrogen decreased the hypertonic saline intake induced by Na + depletion, but it was not associated with any significant changes in the skin Na + reservoir. Thus, sodium depletion is able to change the inactive-active skin Na + reservoir balance. However, the oestrogenic modulation of sodium appetite after Na + depletion is probably not related to the action of this hormone in the skin Na + reservoir balance., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)

Ghrelin is a peptide mainly produced and secreted by the stomach. Since its discovery, the impact of ghrelin on the regulation of food intake has been the most studied function of this hormone; however, ghrelin affects a wide range of physiological systems, many of which are controlled by the hypothalamic paraventricular nucleus (PVN). Several pathways may mediate the effects of ghrelin on PVN neurons, such as direct or indirect effects mediated by circumventricular organs and/or the arcuate nucleus. The ghrelin receptor is expressed in PVN neurons, and the peripheral or intracerebroventricular administration of ghrelin affects PVN neuronal activity. Intra-PVN application of ghrelin increases food intake and decreases fat oxidation, which chronically contribute to the increased adiposity. Additionally, ghrelin modulates the neuroendocrine axes controlled by the PVN, increasing the release of vasopressin and oxytocin by magnocellular neurons and corticotropin-releasing hormone by neuroendocrine parvocellular neurons, while possibly inhibiting the release of thyrotropin-releasing hormone. Thus, the PVN is an important target for the actions of ghrelin. Our review discusses the mechanisms of ghrelin actions in the PVN, and its potential implications for energy balance, neuroendocrine, and integrative physiological control., (© 2019 New York Academy of Sciences.)

Ethnopharmacological Relevance: Medicinal plants widely used by the population contain significant concentrations of biologically active compounds and, although they have proven pharmacological properties, can cause DNA damage and develop fatal diseases., Aim of the Study: The present study aimed to evaluate the genotoxic, cytotoxic potential and clastogenic effects of the aqueous extract from Mangifera indica leaves (EAMI) on rats submitted to experimental genotoxicity models and through the SMART test performed in Drosophila melanogaster., Material and Methods: The comet assay and the micronucleus test were performed on peripheral and bone marrow blood, respectively, of Wistar rats, orally treated with EAMI at doses of 125, 250, 500 and 1000 mg/kg/bw for 28 days. In the SMART test, the standard cross between three mutant D. melanogaster strains was used. Larvae were treated with EAMI at different concentrations, and the wings of adult flies were evaluated for the presence/frequency of mutant spots and compared to the negative control group., Results: Phytochemical analysis of EAMI indicated high levels of flavonoids. The tests performed in rats showed that EAMI did not present significant genotoxic or clastogenic effects. The results showed a critical dose-dependent cytoprotective effect exerted by EAMI. This result was attributed to the high content of polyphenols and flavonoids. The biotransformation metabolites of EAMI did not present genotoxic activity, as demonstrated by the SMART test., Conclusions: These results are relevant since they provide safety information about a plant species of great therapeutic, economical, nutritious and ethnopharmacological value for the population., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The exogenous application of GA 3 to atemoya tree flowers induces parthenocarpy, and in association with artificial pollination, it increases the fruit size. Morphological, anatomical, ultrastructural, and chemical aspects were evaluated during development of (1) fruit produced by artificial pollination (AP), (2) fruit from AP followed by the application of 250 ppm GA 3 , and (3) parthenocarpic fruit induced by the application of 1000 ppm GA 3 . Fruit growth showed a sigmoidal pattern, with development occurring in three phases: (I) cell division, (II) cell differentiation, and (III) maturation. Phase I presented cells with large nuclear volumes and a large population of organelles, phase II presented cells with a reduction in cytoplasm and an increase in vacuole volume, and phase III presented cells with an increase in plastids with reserve compounds. The application of GA 3 , in association with pollination, precedes cytological events and delays when applied exclusively. GA 3 promotes the growth of pollinated fruits by stimulating cell division and expansion, which occur in association with reduced seed production, and the GA 3 induces parthenocarpy by maintaining division and stimulating cell expansion. The absence of seeds accounts for the smaller size of the parthenocarpic fruits, and the lower accumulation of calcium accounts for less firm fruit.

The aim of this study was to evaluate the antimicrobial activity of ethanoic extract of P. amarus (PAEE) and its compound Phyllanthin, as well as, investigate if these natural products could modulate the fluoroquinolone-resistance in S. aureus SA1199-B by way of overexpression of the NorA efflux pump. Microdilution tests were carried out to determine the minimal inhibitory concentration (MIC) of the PAEE or Phyllanthin against several bacterial and yeast strains. To evaluate if PAEE or Phyllanthin were able to act as modulators of the fluoroquinolone-resistance, MICs for Norfloxacin and ethidium bromide were determined in the presence or absence of PAEE or Phyllanthin against S. aureus SA1199-B. PAEE showed antimicrobial activity against Gram-negative strains, meanwhile Phyllanthin was inactive against all strains tested. Addition of PAEE or Phyllanthin, to the growth media at sub-inhibitory concentrations enhanced the activity of the Norfloxacin as well as, Ethidium Bromide, against S. aureus SA1199-B. These results indicate that Phyllanthin is able to modulate the fluoroquinolone-resistance possibly by inhibition of NorA. This hypothesis was supported by in silico docking analysis which confirmed that Phyllantin is a NorA ligand. Thus, this compound could be used as a potentiating agent of the Norfloxacin activity in the treatment of infections caused by fluoroquinolone-resistant S. aureus., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The subfornical organ (SFO) lacks the normal blood-brain barrier and senses the concentrations of many different circulating signals, including glucose and angiotensin II (ANG II). ANG II has recently been implicated in the control of food intake and body weight gain. The present study assessed whether single SFO neurones sense changes in glucose and ANG II, and also whether changes in glucose concentration alter the responsiveness of these neurones to ANG II. SFO neurones dissociated from male Sprague-Dawley rats (100-175 g) were used. We first examined whether glucose concentration modulates AT 1 receptor expression. Similar AT 1a mRNA expression levels were found at glucose concentrations of 1, 5 and 10 mmol L -1 in dissociated SFO neurones. Glucose responsiveness of SFO neurones was assessed using perforated current-clamp recordings and switching between 5 and 10 mmol L -1 glucose artificial cerebrospinal fluid to classify single neurones as nonresponsive (nGS), glucose-excited (GE) or glucose-inhibited (GI). In total, 26.7% of the SFO neurones were GI (n = 24 of 90), 21.1% were GE (n = 19 of 90) and 52.2% were nGS (n = 47 of 90). Once classified, the effects of 10 nmol L -1 ANG II on the excitability of these neurones were tested, with 52% of GE (n = 10 of 19), 71% of GI (n = 17 of 24) and 43% of nGS (n = 20 of 47) neurones being ANG II sensitive. Finally, we tested whether acute changes in glucose concentration modified the response to ANG II and showed that some neurones (4/17) only respond to ANG II at 10 mmol L -1 glucose. Our data demonstrate that the same SFO neurone can sense glucose and ANG II and that acute changes in glucose concentration may change ANG II responsiveness., (© 2018 British Society for Neuroendocrinology.)

Background: Pathways to care are actions and strategies employed by individuals in order to get help for health-related distress and the related processes of care providers. On several systematic reviews regarding pathways to mental health care (PMHC), studies regarding South American countries were not present. This review synthesizes qualitative and quantitative research about PMHC in Brazil., Methods: LILACS, MEDLINE and SCIELO databases were searched for papers regarding PMHC in Brazil. The results were organized in pathway stages, based on Goldberg and Huxley's 'model of Levels and Filters' and on Kleinman's framework of 'Popular, Folk and Professional health sectors'. Analysis also considered the changes in national mental health policy over time., Results: 25 papers were found, with data ranging from 1989 to 2013. Complex social networks were involved in the initial recognition of MH issues. The preferred points of first contact also varied with the nature and severity of problems. A high proportion of patients is treated in specialized services, including mild cases. There is limited capacity of primary care professionals to identify and treat MH problems, with some improvement from collaborative care in the more recent years. The model for crisis management and acute care remains unclear: scarce evidence was found over the different arrangements used, mostly stressing lack of integration between emergency, hospital and community services and fragile continuity of care., Conclusions: The performance of primary care and the regulation of acute demands, especially crisis management, are the most critical aspects on PMHC. Although primary care performance seems to be improving, the balanced provision and integration between services for adequate acute and long-term care is yet to be achieved.

Aim: To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia (HEEP) leaves on gastric ulcer healing., Methods: In this rat study involving males, intact (cycling) females, and ovariectomized females, gastric ulcers were induced using acetic acid. A vehicle, lansoprazole, or HEEP was administered for 14 d after ulcer induction. Body weight was monitored throughout the treatment period. At the end of treatment, the rats were euthanized and the following in vivo and in vitro investigations were performed: macroscopic examination of the lesion area and organ weights, biochemical analysis, zymography, and evaluation of protein expression levels. Additionally, the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity., Results: Compared to the vehicle, HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males (52.44%), intact females (85.22%), and ovariectomized females (65.47%), confirming that HEEP accelerates the healing of acetic acid-induced gastric lesions and suggesting that this effect is modulated by female sex hormones. The antiulcer effect of HEEP was mediated by prostaglandin E 2 only in male rats. Overall, the beneficial effect of HEEP was the highest in intact females. Notably, HEEP promoted the expression of vascular endothelial growth factor (intact vs ovariectomized females) and decreased the expression of Caspase-8 and Bcl-2 (intact female vs male or ovariectomized female). Additionally, HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro , confirming its healing effect. Finally, no sign of subacute toxicity or cytotoxicity of HEEP was observed., Conclusion: In gastric ulcers, HEEP-induced healing (modulated by female sex hormones; in males, mediated by prostaglandin) involves extracellular matrix remodeling, with gastric mucosa cell proliferation and migration., Competing Interests: Conflict-of-interest statement: The authors declare that they have no commercial, personal, political, intellectual, or religious interests related to the work presented herein.

High-mobility group B (HMGB) proteins have highly conserved, unique DNA-binding domains, HMG boxes, that can bind non-B-type DNA structures, such as bent, kinked and unwound structures, with high affinity. HMGB proteins also promote DNA bending, looping and unwinding. In this study, we determined the role of the Aedes aegypti single HMG-box domain protein AaHMGB; characterized its structure, spatiotemporal expression levels, subcellular localization, and nucleic acid binding activities; and compared these properties with those of its double-HMG-box counterpart protein, AaHMGB1. Via qRT-PCR, we showed that AaHMGB is expressed at much higher levels than AaHMGB1 throughout mosquito development. In situ hybridization results suggested a role for AaHMGB and AaHMGB1 during embryogenesis. Immunolocalization in the midgut revealed that AaHMGB is exclusively nuclear. Circular dichroism and fluorescence spectroscopy analyses showed that AaHMGB exhibits common features of α-helical structures and is more stably folded than AaHMGB1, likely due to the presence of one or two HMG boxes. Using several DNA substrates or single-stranded RNAs as probes, we observed significant differences between AaHMGB and AaHMGB1 in terms of their binding patterns, activity and/or specificity. Importantly, we showed that the phosphorylation of AaHMGB plays a critical role in its DNA-binding activity. Our study provides additional insight into the roles of single- versus double-HMG-box-containing proteins in nucleic acid interactions for better understanding of mosquito development, physiology and homeostasis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The paraventricular nucleus (PVN) is involved in the control of sympathetic tone and the secretion of hormones, both functions known to be influenced by ghrelin, suggesting direct effect of ghrelin in this nucleus. However, the effects of ghrelin on the excitability of different PVN neuronal populations have not been demonstrated. This study assessed the effects of ghrelin on the activity of PVN neurons, correlating the responses to subpopulations of PVN neurons. We used a 64 multielectrode array to examine the effects of ghrelin administration on extracellular spike frequency in PVN neurons recorded in brain slices obtained from male Sprague-Dawley rats. Bath administration of 10 nM ghrelin increased (29/97, 30%) or decreased (37/97, 38%) spike frequency in PVN neurons. The GABAA and glutamate receptors antagonists abolish the decrease in spike frequency, without changes in the proportion of increases in spike frequency (23/53, 43%) induced by ghrelin. The results indicate a direct effect of ghrelin increasing PVN neurons activity and a synaptic dependent effect decreasing PVN neurons activity. The patch clamp recordings showed similar proportions of PVN neurons influenced by 10 nM ghrelin (33/95, 35% depolarized; 29/95, 30% hyperpolarized). Using electrophysiological fingerprints to identify specific subpopulations of PVN neurons we observed that the majority of pre-autonomic neurons (11/18 -61%) were depolarized by ghrelin, while both neuroendocrine (29% depolarizations, 40% hyperpolarizations), and magnocellular neurons (29% depolarizations, 21% hyperpolarizations) showed mixed responses. Finally, to correlate the electrophysiological response and the neurochemical phenotype of PVN neurons, cell cytoplasm was collected after recordings and RT-PCR performed to assess the presence of mRNA for vasopressin, oxytocin, thyrotropin (TRH) and corticotropin (CRH) releasing hormones. The single-cell RT-PCR showed that most TRH-expressing (4/5) and CRH-expressing (3/4) neurons are hyperpolarized in response to ghrelin. In conclusion, ghrelin either directly increases or indirectly decreases the activity of PVN neurons, this suggests that ghrelin acts on inhibitory PVN neurons that, in turn, decrease the activity of TRH-expressing and CRH-expressing neurons in the PVN.