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Chagas disease (CD) is a life-threatening illness caused by the protozoan Trypanosoma cruzi and there are only two drugs currently available for pharmacotherapy of this neglected infection (benznidazole and nifurtimox). Their limited efficacy in chronic phase of the disease, problems of toxicity and the growing resistance by the protozoan are directly associated to high rates of drug discontinuation by the patients. In the context of the search for new trypanocidal drug candidates, our group has been working with the chemical manipulation of eugenol to obtain new agents active against T. cruzi and promising results have been achieved. In this work we designed molecular hybrids between eugenol and benznidazole (BZN) by performing a bioisosteric replacement between the nitroimidazole ring of BZN by the eugenol or analogues nucleus in nitrated or non-nitrated forms. The obtained compounds were initially evaluated against epimastigote stages of T. cruzi for selecting the most active ones. Three hybrids (8, 10 and 15) showed activity against this evolutive stage and the most promising was eugenol nitro derivative 8 (IC 50 : 24.7 µM) that showed a similar potential than BZN (IC 50 : 29.9 µM). Compounds 8, 10 and 15 were then evaluated against infective trypomastigote and intracellular amastigote forms of T. cruzi and the cytotoxicity of them was investigated against healthy Vero and H9c2 cells. The nitro derivative 8 was once again the most promising compound against trypomastigote (IC 50 : 1.8 µM) and amastigote (IC 50 : 1.6 µM) forms, with selectivity indices greater than 63 considering both health cells evaluated. This compound was more active than BZN, that showed IC 50 values of 6.1 µM (trypomastigotes) and 3.1 µM (amastigotes) and showed the most significant effect in reducing the infection rate and accumulation of parasites in infected cells. Calculated logP values suggest that the higher lipophilicity of derivative 8 (clogP: 3.25) in relation to BZN (clogP: 0.77) may be correlated to a greater ability of this eugenol derivative to cross the membranes of infected cells. Finally, to try understand the possible mode of action for compound 8, we have evaluated three important targets of the parasite (T. cruzi nitroreductase type I - TcNRT, trypanothione reductase - TR and mitochondrial membrane depolarization), but none of these metabolic pathways seem to be related to the mechanism of action of this compound. All in vitro assays employed the T. cruzi Y strain which exhibits partial resistance to benznidazole and these results indicate compound 8 as a new promising hit for the development of drug candidates to treat CD., 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 Inc. All rights reserved.)

Galactoglucomannan (GGM) is the predominant hemicellulose in coniferous trees, such as Norway spruce, and has been used as a multipurpose emulsifier in the food industry. In vitro digestion with a cellular antioxidant activity assay was performed to determine the bioaccessibility and antioxidant activity of phenolic compounds, and the behaviour of GGM on in vivo experimental assay against induced colon cancer. The results showed that digestion decreased the bioaccessibility and antioxidant capacity of phenolic compounds. Cellular analysis did not support these findings once an antioxidant effect was observed in human cell lines. GGM attenuated the initiation and progression of colon cancer, by reducing the foci of aberrant crypts in rats, and modified the intestinal bacterial microbiota (disrupting the balance between Firmicutes and Bacteroidetes phyla). Thus, GGM provided chemopreventive protection against the development of colon cancer and acted as an intracellular antioxidant agent., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Luciana Azevedo reports financial support was provided by Minas Gerais State Foundation of Support to the Research. Luciana Azevedo reports financial support was provided by National Council for Scientific and Technological Development., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

When an insect walks, it leaves chemical cues that derive from the arolium, a tarsal structure. These cues may contain important information about other species that occur in their community and can then mediate interactions of competition, predation, and information about resources with ants from their own colony. The compounds of these cues are released into the substrate in the form of chemical footprints. There are still few species studied, and little is known about the behavior of ants regarding these signals and how they use them in their interactions. Therefore, the aim of this study was to assess the behavioral strategy of different ant species when confronted with chemical footprints left by other ants, as well as identify their compounds and their relationship with the cuticular hydrocarbon profile. The experiments were performed using a Y-maze, where in one of the arms, there were chemical footprints of their own species or of other species, and the other Y arm was footprint-free. The chemical compounds of footprints and cuticle were analyzed by gas chromatography-mass spectrometry. The results show that foragers of all species detect and respond to the presence of chemical cues in the form of footprints left by other ants. Foragers of all species followed footprints of individuals of the same species both nestmates and non-nestmates; however, Neoponera villosa avoided the footprints of Cephalotes borgmeieri, and C. borgmeieri avoided the footprints of the other two species. The chemical compositions of the cuticle and footprints are related to each other and are specific to each species., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objective: Reduced functional capacity, dyspnea, fatigue, and changes in body composition are common in patients with post-COVID-19 syndrome (PCS), and cardiopulmonary rehabilitation may improve these parameters. Thus, the present study verified the effects of cardiopulmonary rehabilitation (respiratory, aerobic, and resistance muscle training) on submaximal exercise tolerance, dyspnea, fatigue, and body composition., Methods: This controlled and randomized clinical trial applied a six-week outpatient intervention protocol in individuals over 18 years old (n = 33) with a diagnosis of COVID-19 confirmed by polymerase chain reaction. These individuals were allocated to cardiopulmonary rehabilitation (n = 17) or control groups (i.e., educational lectures; n = 16). The cardiopulmonary rehabilitation group performed respiratory, aerobic, and resistance muscle training. Submaximal exercise tolerance, dyspnea, fatigue, and body composition were assessed before and after the protocol., Results: After 6 weeks, the cardiopulmonary rehabilitation group increased the tolerance to submaximal exercise, with a difference of 100.46 m (95% confidence interval [CI]: 7.40-193 m) in the distance walked on the six-minute walk test, reduced dyspnea (-1.45, 95% CI: -1.98--0.92) in the modified Medical Research Council, and increased 0.63 kg (95% CI: 0.09-1.18 kg) of muscle mass in the upper limbs compared with the control group., Conclusion: The six-week cardiopulmonary rehabilitation protocol improved functional capacity, reduced dyspnea, and increased muscle mass in the upper limbs in individuals with PCS. Thus, these results supported the protocol use in this population and encourage further studies to assess its effectiveness in a large sample., (© 2024 John Wiley & Sons Ltd.)

Chagas disease (CD) is a neglected tropical disease endemic in 21 countries and affects about 8 million people around the world. The pharmacotherapy for this disease is limited to two drugs (Benznidazole and Nifurtimox) and both are associated with important limitations, as low cure rate in the chronic phase of the disease, high toxicity and increasing resistance by Trypanosoma cruzi. Recently, we reported a bioactive 1,2,3-triazole (compound 35) active in vitro (IC 50 42.8 μM) and in vivo (100 mg/kg) against T. cruzi Y strains and preliminary in silico studies suggested the cysteine protease cruzain as a possible target. Considering these initial findings, we describe here the design and synthesis of new 1,2,3-triazoles derivatives of our hit compound (35). The triazoles were initially evaluated against healthy cells derived from neonatal rat cardiomyoblasts (H9c2 cells) to determine their cytotoxicity and against epimastigotes forms of T. cruzi Y strain. The most active triazoles were compounds 26 (IC 50 19.7 μM) and 27 (IC 50 7.3 μM), while benznidazole was active at 21.6 μM. Derivative 27 showed an interesting selectivity index considering healthy H9c2 cells (>77). Promising activities against trypomastigotes forms of the parasite were also observed for triazoles 26 (IC 50 20.74 μM) and 27 (IC 50 8.41 μM), mainly 27 which showed activity once again higher than that observed for benznidazole (IC 50 12.72 μM). While docking results suggested cruzain as a potential target for these compounds, no significant enzyme inhibition was observed in vitro, indicating that their trypanocidal activity is related to another mode of action. Considering the promising in vitro results of triazoles 26 and 27, the in vivo toxicity was initially verified based on the evaluation of behavioral and physiological parameters, mortality, effect in body weight gain, and through the measurement of AST/ALT enzymes, which are markers of liver toxicity. All these evaluations pointed to a good tolerability of the animals, especially considering triazole 27. A reduction in parasitemia was observed among animals treated with triazole 27, but not among those treated with derivative 26. Regarding the dosage, derivative 27 (100 mg/kg) was the most active sample against T. cruzi infection, showing a 99.4% reduction in parasitemia peak. Triazole 27 at a dosage of 100 mg/kg influenced the humoral immune response and reduced myocarditis in the animals, bringing antibody levels closer to those observed among healthy mice. Altogether, our results indicate compound 27 as a new lead for the development of drug candidates to treat Chagas disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Map Interventions is capable of supporting the multidisciplinary team that works in organ and tissue donation to disseminate quality in this process., Methods: A scoping review study that was conducted through the steps proposed by the Joanna Briggs Institute., Results: Fifty-six studies made up the sample. 2018 (no. 07, 12.5%) had the highest number of publications. The country that published the most was the United States (no. 16, 28.56%). The database with the most publications was the Cumulative Index to Nursing and Allied Health Literature - CINAHL (no. 15, 26.78%). The most used interventions, which had the most significant impact on the improvement of results and quality, were the use of indicators in all stages of the organ and tissue donation process; the use of real goals that can be achieved; frequent audits, validation of instruments to track opportunities for improvement; as well as methodologies to implement quality and education among professionals who work in this process. Such interventions reveal important changes in the organ donation process, especially in the notification of potential and effective donors, as well as providing an opportunity for safety in the stages of the organ and tissue donation process., Conclusion: The interventions tracked suggest the implementation of a set of actions formed by the continuous use of auditing, indicators, continuing education with the team that works in the process of organ and tissue donation, combined with the management of the results obtained through the indicators, where it is generated from these data, actions that have a direct impact on the weaknesses identified., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The modulation of inflammatory elements, cell differentiation and proliferation by vitamin D and the role of probiotics in the intestinal microbiota and immunogenic response have sparked interest in the application of both in chemotherapeutics and chemoprevention of colorectal tumors., Aims: The present study aimed to investigate the effects of isolated and/or combined treatment of vitamin D3 and probiotics on colorectal carcinogenesis., Main Methods: Pre-neoplastic lesions were induced with 1,2-dimethylhydrazine in the colon of Wistar rats, which were treated with probiotics and/or vitamin D in three different approaches (simultaneous, pre-, and post-treatment). We investigated the frequency of aberrant crypt foci (ACF) and aberrant crypt (AC) in the distal colon, fecal microbiome composition, gene and protein expression through immunohistochemical and RT-PCR assays, and general toxicity through water consumption and weight gain monitoring., Key Findings: Results confirm the systemic safety of treatments, and show a protective effect of vitamin D and probiotics in all approaches studied, as well as in combined treatments, with predominance of different bacterial phyla compared to controls. Treated groups show different levels of Nrf2, GST, COX2, iNOS, β-catenin and PCNA expression., Significance: These experimental conditions explore the combination of vitamin D and probiotics supplementation at low doses over pathways involved in distinct stages of colorectal carcinogenesis, with results supporting its application in prevention and long-term strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to verify if there is a relationship between self-reported pain, PPT (pressure pain threshold) of the masseter, temporal and sternocleidomastoid muscles, pain catastrophizing and quality of life in patients with TMD (temporomandibular disorder) of muscular origin., Material and Methods: Ninety-seven patients with muscular TMD (TMD group) and 97 asymptomatic (control group) were included in the study. The evaluation methods used were: 1) Self-reported pain was assessed using the Visual Analogue Scale (VAS) for questions 7, 8 and 9 of the RDC/TMD Axis I questionnaire; 2) The PPT assessment was performed using a digital algometer on the masseter, temporal, and sternocleidomastoid muscles (both sides); 3) Pain catastrophizing was assessed using the PCS (Pain Catastrophizing Scale); and 4) Oral health-related quality of life was assessed using the OHIP-14 (Oral Healthy Impact Profile-14). Data were submitted to Spearman correlation and logistic regression ( p <0.05)., Results: There were significant positive correlations between self-reported pain (VAS-Q7, VAS-Q8 and VAS-Q9), pain catastrophizing (PCS-Helplessness, PCS-Magnification, PCS-Rumination and PCS-Total) and quality of life (OHIP-14) ( p <0.05). There was a significant negative correlation of self-reported pain (VAS-Q8) with PPT of the temporal (left) and sternocleidomastoid (both sides) ( p <0.05). The rumination and magnification domains increased the chance of high self-reported pain in all situations (VAS-Q7, VAS-Q8 and VAS-Q9) ( p <0.05). The helplessness domain only increased the chance of high self-reported pain for VAS-Q8 ( p <0.05). The presence of TMD of muscular origin, high self-reported pain (VAS-Q7) or pain catastrophizing increased the chance of a low quality of life in relation to the control group ( p <0.05). In addition, the reduction in sternocleidomastoid PPT increased the chance of poor quality of life ( p <0.05). Key words: Myofascial pain syndromes, pain catastrophizing, myalgia, quality of life, surveys and questionnaires, temporomandibular joint disorders., Competing Interests: Conflicts of interest None of the authors has any conflict of interest related to the conduct of this study., (Copyright: © 2023 Medicina Oral S.L.)

Gliomas are the most common primary malignant brain tumors in adults, and have a poor prognosis, despite the different types of treatment available. There is growing demand for new therapies to treat this life-threatening tumor. Quinone derivatives from plants have received increased interest as potential anti-glioma drugs, due to their diverse pharmacologic activities, such as inhibiting cell growth, inflammation, tumor invasion, and promoting tumor regression. Previous studies have demonstrated the anti-glioma activity of Eleutherine plicata , which is related to three main naphthoquinone compounds-eleutherine, isoeleutherine, and eleutherol-but their mechanism of action remains elusive. Thus, the aim of this study was to investigate the mechanism of action of eleutherine on rat C6 glioma. In vitro cytotoxicity was evaluated by MTT assay; morphological changes were evaluated by phase-contrast microscopy. Apoptosis was determined by annexin V-FITC-propidium iodide staining, and antiproliferative effects were assessed by wound migration and colony formation assays. Protein kinase B (AKT/pAKT) expression was measured by western blot, and telomerase reverse transcriptase mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Eleutherine reduced C6 cell proliferation in a dose-dependent manner, suppressed migration and invasion, induced apoptosis, and reduced AKT phosphorylation and telomerase expression. In summary, our results suggest that eleutherine has potential clinical use in treating glioma.

Ayahuasca is a psychoactive and psychedelic decoct composed mainly of Banisteriopsis caapi and Psychotria viridis plant species. The beverage is rich in alkaloids and it is ritualistically used by several indigenous communities of South America as a natural medicine. There are also reports in the literature indicating the prophylaxis potential of Ayahuasca alkaloids against internal parasites. In the present study, Ayahuasca exhibited moderate in vitro activity against Trypanosoma cruzi trypomastigotes (IC 50 95.78 μg/mL) compared to the reference drug benznidazole (IC 50 2.03 μg/mL). The β-carboline alkaloid harmine (HRE), isolated from B. caapi, was considered active against the trypomastigotes forms (IC 50 6.37), and the tryptamine N, N-dimethyltryptamine (DMT), isolated from P. viridis was also moderately active with IC 50 of 21.02 μg/mL. Regarding the in vivo evaluations, no collateral effects were observed. The HRE alone demonstrated the highest trypanocidal activity in a dose-responsive manner (10 and 100 mg/kg). The Ayahuasca and the association between HRE and DMT worsened the parasitaemia, suggesting a modulation of the immunological response during the T. cruzi infection, especially by increasing total Immunoglobulin (IgG) and IgG1 antibody levels. The in silico molecular docking revealed HRE binding with low energy at two sites of the Trypanothione reductase enzyme (TR), which are absent in humans, and thus considered a promissory target for drug discovery. In conclusion, Ayahuasca compounds seem to not be toxic at the concentrations of the in vivo evaluations and can promote trypanocidal effect in multi targets, including control of parasitaemia, immunological modulation and TR enzymatic inhibition, which might benefit the treatments of patients with Chagas' disease. Moreover, the present study also provides scientific information to support the prophylactic potential of Ayahuasca against internal parasites., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

The molluscicidal action of essential oils have been attributed to the most prevalent terpene compounds. However, molluscicidal properties, mode of action, and toxicity to non-target organisms remain unclear. In this study, the molluscicidal potential of four monoterpenes (camphor, thymol, α-pinene, and 1,8-cineole) against the snail Biomphalaria glabrata, an intermediate host of Schistosoma mansoni, was analyzed. The molluscicide activity of each monoterpene was assessed by the standardized test of the World Health Organization (WHO) and the monoterpenes considered active against B. glabrata were analyzed as inhibitors of the enzymatic activity of acetylcholinesterase (AChE) extracted from snails. In addition, acute toxicity to non-target organisms was assessed against Danio rerio fish. The results show that camphor and 1,8-cineole monoterpenes did not induce snail mortality. Thymol and α-pinene were active against B. glabrata, inducing mortality in concentration-dependent patterns and showing a lethal effect in concentrations compatible with that recommended by the WHO (LC 90 of 7.11 and LC 90 10.34 μg ∙ mL -1 , respectively). The toxic action of thymol and α-pinene on snails indicates that these monoterpenes may account for or largely contribute to the molluscicidal activity of essential oils that contain them as major compounds. Thymol and α-pinene inhibit the AChE of B. glabrata at concentrations higher than those used in the molluscicide test. These monoterpenes show low toxicity to non-target organisms compared to the commercial molluscicide niclosamide. Knowledge about monoterpene toxicity against B. glabrata contributes to its potential use in molluscicidal formulations and in alternatives to the control of snails that host intermediate S. mansoni, a crucial action in the prevention and transmission of schistosomiasis, a neglected tropical disease., (Copyright © 2021. Published by Elsevier B.V.)

Hundreds of millions of people worldwide are affected by Chagas' disease caused by Trypanosoma cruzi. Since the current treatment lack efficacy, specificity, and suffers from several side-effects, novel therapeutics are mandatory. Natural products from endophytic fungi have been useful sources of lead compounds. In this study, three lactones isolated from an endophytic strain culture were in silico evaluated for rational guidance of their bioassay screening. All lactones displayed in vitro activity against T. cruzi epimastigote and trypomastigote forms. Notably, the IC 50 values of (+)-phomolactone were lower than benznidazole (0.86 vs. 30.78 μM against epimastigotes and 0.41 vs. 4.88 μM against trypomastigotes). Target-based studies suggested that lactones displayed their trypanocidal activities due to T. cruzi glyceraldehyde-3-phosphate dehydrogenase (TcGAPDH) inhibition, and the binding free energy for all three TcGAPDH-lactone complexes suggested that (+)-phomolactone has a lower score value (-3.38), corroborating with IC 50 assays. These results highlight the potential of these lactones for further anti-T. cruzi drug development., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Generalized tonic-clonic seizures (GTCS) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Also, among the several mechanisms underlying SUDEP there is the cardiac dysfunction. So, we aimed to evaluate the impact of the number of seizures on heart function and morphology in rats with epilepsy. Rats were randomized into three groups: Sham (without epilepsy), 5 S, and 10 S groups, referred as rats with epilepsy with a total of 5 or 10 GTCS, respectively. Epilepsy was induced by electrical amygdala kindling. The ventricular function was analyzed by the Langendorff technique and challenged by ischemia/reperfusion protocol. Cardiac fibrosis and hypertrophy were analyzed by histology. We also analyzed cardiac metalloproteinases (MMP2 and MMP9), ERK 1/2 and phosphorylated ERK1/2 (P-ERK) by western blot; microRNA-21 and -320 by RT-PCR; and oxidative stress (TBARS, catalase activity and nitrite) by biochemical analysis. Only the 5S group presented decreased values of ventricular function at before ischemia/reperfusion (baseline): intraventricular systolic pressure, developed intraventricular pressure, positive and negative dP/dt. During ischemia/reperfusion protocol, the variation of the ventricular function did not differ among groups. Both 5S and 10S groups had increased cardiomyocyte hypertrophy and fibrosis compared to Sham, but in the 5S group, these alterations were higher than in the 10S group. The 5S group increased in microRNA-21 and decreased in microRNA-320 expression compared to Sham and the 10S group. The 10S group increased in MMP9 and decreased in P-ERK/ERK expression, and increased in nitrite content compared to both Sham and the 5S group. Therefore, seizures impair cardiac function and morphology, probably through microRNA modulation. The continuation of seizures seems to exert a preconditioning-like stimulus that fails to compensate the cardiac tissue alteration., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Photodynamic therapy (PDT) is a treatment for the specific control of oral biofilms. However, its effects on maxillofacial prostheses have been barely explored. In this study, we evaluated the antimicrobial effect of PDT using methylene blue (MB) and laser against a Staphylococcus aureus biofilm developed on the surface of scleral acrylic resin., Methods: Sixty-six specimens of acrylic resin designed for ocular prostheses were fabricated in a disk-shaped format (3 × 10 mm). S. aureus biofilm was grown on the surface of the specimens for 24 h and the disks were then treated with MB at different concentrations (25, 50, 75 or 100 μg/mL), with or without PDT (GaAlAs diode laser; 660 nm; 100 mW; 9 J; 321.4 J.cm -2 ; 3.5 W.cm -2 and 90 s). Control groups were treated with 2% chlorhexidine gluconate (CHX) or phosphate buffered saline. After the treatments, colony forming units (CFU) were counted and the samples were qualitatively evaluated by scanning electron microscopy (SEM). Data were analyzed descriptively and by nested ANOVA and the Tukey test (α = .05)., Results: PDT groups with MB concentrations at 75 and 100 μg/mL formed fewer CFU compared to the other groups (P < 0.001) and the 2% CHX group did not form any CFU. SEM images revealed that the surface of the polymers in these groups did not show bacterial colonies., Conclusions: PDT significantly reduced S. aureus biofilm in the scleral acrylic resin when associated with an MB dilution of 75 μg/mL or higher. Thus, PDT can be a promising candidate for disinfecting ocular prostheses., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The vital enzyme O-linked β-N-acetylglucosamine transferase (OGT) catalyzes the O-GlcNAcylation of intracellular proteins coupling the metabolic status to cellular signaling and transcription pathways. Aberrant levels of O-GlcNAc and OGT have been linked to metabolic diseases as cancer and diabetes. Here, a new series of peptidomimetic OGT inhibitors was identified highlighting the compound LQMed 330, which presented better IC 50 compared to the most potent inhibitors found in the literature. Molecular modeling study of selected inhibitors into the OGT binding site provided insight into the behavior by which these compounds interact with the enzyme. The results obtained in this study provided new perspectives on the design and synthesis of highly specific OGT inhibitors., Competing Interests: Declaration of Competing Interest I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. I declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Among the members of purinergic receptors, the family P2X of ionotropic proteins has the ion channel subtype P2X7 that show in studies to be an important molecular target for new drugs. The activity of human P2X7 receptor (hP2X7r) in the body, due to its pro-inflammatory function, can trigger physiological disorders related to chronic inflammatory processes, leading to neural degeneration, neuropathic pain and chronic pain. Recently, two series of promising new inhibitors of the hP2X7r ion channel have been reported. One series consisted of naphthoquinone derivatives and the other composed of triazole derivatives. The main objective of this study was to understand the binding mode differences between the hit compounds of each series and compare them to the native ligand ATP. The hP2X7r ion channel and membrane lipid models were prepared in order to allow study the appropriate protein molecular dynamics. Molecular modeling and molecular dynamics simulation approaches were applied in order to obtain atomistic and molecular details that are involved in intermolecular interactions. Both compounds AN-04 and 9d seem to have affinity to binding in the hP2X7r pore area according to molecular dynamics simulations results. The naphthoquinone derivative AN-04 demonstrated a binding free energy 7.68 fold larger than triazole derivative 9d and 3.8 fold lower than native ligand ATP. These results indicate that compound AN-04 might be a promising lead compound for the development of a novel selective hP2X7r inhibitor., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A series of 11 new N,S-acetal juglone derivatives were synthesized and evaluated against T. cruzi epimastigote forms. These compounds were obtained in good to moderate yields using a microwave irradiation protocol. Among all compounds, two N,S-acetal analogs, showed significant trypanocidal activity. Notably, one compound 11g exhibited selectivity index 10-fold higher than the reference drug benznidazole for epimastigote. The compound 11h was more effective for amastigote forms. Both prototypes exhibited S.I. higher than the benznidazole description. Thus, both compounds proving to be useful candidate molecules to further studies in infected animals.

Objective: This study aimed to evaluate the quality of life of patients with oral or oropharyngeal cancer by using specific questionnaires (QLQ-C30 and QLQ-HandN35), varying according to the location of the tumor (oral cavity or oropharynx) and the treatment performed (only surgery or surgery associated with radiotherapy)., Methods: Fifty patients were enrolled in this study and answered the EORTC QLQ-C30 and EORTC HandN35 questionnaires, before (baseline), at 1 week, and 3 months after treatment. Internal consistency reliability was calculated with the Cronbach coefficient. The Kruskal-Wallis and Wilcoxon tests were applied and P.

Endophytic fungi live inside vegetal tissues without causing damage to the host plant and may provide lead compounds for drug discovery. The co-culture of two or more endophytic fungi can trigger silent gene clusters, which could lead to the isolation of bioactive compounds. In this study, two endophytic strains isolated from Handroanthus impetiginosus leaves, identified as Talaromyces purpurogenus H4 and Phanerochaete sp. H2, were grown in mixed and axenic cultures. The meroterpenoid austin was detected only in the extracts from the mixed culture. Once isolated, austin displayed very interesting trypanocidal activity, with an IC 50 value of 36.6 ± 1.2 μg/mL against Trypanosoma cruzi in the epimastigote form. The results obtained highlight the importance of the co-culturing of endophytic fungi to obtain natural bioactive products. The findings also enhance our understanding of the ecological relationships between endophytic fungi.

Background: The aim of the present study was to investigate pain perception and anxiety within the context of surgery for the placement of mandibular block bone and to evaluate the causality effect between theses variables., Material and Methods: A total of 13 patients were recruited for the study and were submitted to mandibular autogenous block bone surgery. Demographic data were collected and the anxiety level was determined using the State-Trait Anxiety Inventory (STAI). The STAI was administered on the day of surgery and on the 14th postoperative day. Pain was determined using the visual analogue scale (VAS) and limitation of daily activities and postoperative symptoms were also reported. Data were analyzed using parametric tests (α=0.05) and cross-lagged analysis was performed to verify a causality effect., Results: Few patients reported interference with daily activities or the presence of postoperative symptoms. A significant association of bad breath/taste with STAI-State was detected on the 14th postoperative day. No evidence of causality between STAI and VAS was detected., Conclusions: The patient's self-evaluation indicates that the pain and anxiety level felt during treatment was not directly associated with the clinical aspects of the surgical procedure or with postoperative activities/symptoms limitations. Key words: Anxiety pain, questionnaires, autogenous bone block, treatment, outcomes., Competing Interests: Conflicts of interest The authors do not have any conflicts of interest., (Copyright: © 2020 Medicina Oral S.L.)

This study was performed to evaluate the linear and volumetric effects of a technique for reconstruction of the posterior atrophic mandible, including the final bone gain of the graft, by three-dimensional assessment. Thirteen individuals were recruited into the study and submitted to a total of 15 mandibular autogenous bone block surgeries. Cone beam computed tomography images were obtained at three different times. Bone graft length and thickness, and the volume, height, and width of the graft were measured. Data were compared statistically among the time points using the Friedman test, and cluster analysis was performed to identify the association between the study variables and the resorption rate (α = 0.05). Linear analysis of the width and height of the recipient area at the different time points revealed a statistically significant difference. The final average increase in height was 1.6 mm; all subjects showed an average volume gain of 3.412mm 3 , and 77% of the subjects showed an average graft resorption of 0.688mm 3 construction of three-dimensional vertical defects of the posterior mandible resulted in good healing with minimal complications and minimal bone graft resorption, favouring vertical bone gain., (Copyright © 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Statement of Problem: Maxillofacial elastomers undergo physical and mechanical degradation with disinfecting solutions. Solutions of Brazilian green propolis extract may be suitable alternatives for infection control of maxillofacial prostheses. However, their effects on the properties of the material are unknown., Purpose: The purpose of this in vitro study was to evaluate the effect of disinfection with solutions of Brazilian green propolis extract on the transmittance, translucency parameter, contrast ratio, and hardness of 2 maxillofacial elastomers (MDX4-4210 and MED-4014)., Material and Methods: Fifty disk-shaped specimens (3×10 mm) of each elastomer were randomly and equally divided into 4 groups of disinfectant agents and 1 control group: 3 separate groups of 11% green propolis extracts including aqueous (PAQ), glycolic (PGL), and alcoholic (PAL), a 2% chlorhexidine gluconate (CHX) group, and the control group of distilled water. Specimens were subjected to disinfection by immersion 3 times a week for 60 days. Color differences (ΔE values) were calculated with CIELab and CIEDE2000 formulas. Optical parameters and Shore A hardness were determined at 2 time points: at baseline and after the period of specimen disinfection. Data were analyzed by parametric and nonparametric analysis of variance and by multiple-comparison tests (α=.05)., Results: The ΔE values of specimens immersed in 11% PAL were not clinically acceptable for either elastomer. Regarding translucency parameter and contrast ratio, the immersion in 11% PAL and 11% PGL resulted in greater opacity and lower translucency of the material. Mean Shore A hardness values were not statistically significantly different at baseline or after 60 days of immersion in the solutions., Conclusions: The solution of Brazilian green propolis extract tested showed changes in optical parameters. Elastomers immersed in 11% alcoholic green propolis extract showed clinically unacceptable color and translucency changes. All hardness values of the tested elastomers were clinically acceptable after immersion in all tested disinfectant groups., (Copyright © 2019 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Natural and synthetic coumarins have been described as prototypes of new drug candidates against Chagas' disease. During a typical screening with new compounds, we observed the potential of a new synthetic nitrobenzoylcoumarin (1) as trypanocidal against Trypanosoma cruzi epimastigotas. Then, we decided to prepare and evaluate a set of analogues from 1 to check the major structural requirements for trypanocidal activity. The structural variations were conducted in six different sites on the original compound and the best derivative (3) presented activity (IC 50 28 ± 3 μM) similar to that of benznidazole (IC 50 25 ± 10 μM). The enhancement of trypanocidal activity was conditioned to a change in the side chain at C6 (allyl to n-propyl group) and the preservation of coumarin nucleus and the nitrobenzoyl group at C3. Exposure of 3 to H9C2 cells showed low toxicity (CC 50  > 200 μM) and its activity on T. cruzi amastigotes (IC 50 13 ± 0.3 μM) encouraged us to perform an evaluation of its potential when given orally to mice infected with trypomastigote forms. Derivative 3 was able to reduce parasitemia when compared to the group of untreated animals. Taken together, these results show the potential therapeutic application of the synthetic coumarins., (© 2018 John Wiley & Sons A/S.)

The cyanobacterium Cylindrospermopsis raciborskii is an invasive species in water supply reservoirs worldwide, which can produces cylindrospermopsins and saxitoxins. In the wild, guppy (Poecilia vivipara) can be exposed to cyanotoxins, but those born and reared in laboratory are free of this contact. The aim of this paper was to comparatively measure the locomotor activity of 'wild' and 'lab' P. vivipara before and after exposure to crude extracts of two different cultures of C. raciborskii (CYRF-01), a saxitoxin-procucer strain. The movement of each fish was recorded using an image monitoring system (Videomex V ® ) before and after 48 h exposure to cyanobacterial extracts. Each experiment was performed during 4 h, with 1 h acclimation and 3 h recording period of the parameters Distance performed (DP), Swimming time (SwT), Stereotypic time (StT), Resting time (RT) and Average speed (AS). The quantification of saxitoxin in the solutions was performed by the enzyme-linked immunosorbent assay (ELISA). The weight or the total length did not influence the locomotor activity of fish in any of the experiments. The saxitoxin value was similar for both cultures (Culture 1: 7.3 μg L -1 and Culture 2: 8.6 μg L -1 ). However, in experiments with Culture 1 an increased activity in most parameters was observed, while in Culture 2, a decreased activity was observed only in 'lab' fish. Wild fish was less affected, showing higher resistance to both cyanobacterial crude extracts. This study showed that different cultures of the same strain of C. raciborskii and with similar contents of saxitoxin are able to change the locomotor activity of P. vivipara, contributing to the validation of the use of behavioral parameters to the evaluation of sublethal effects of toxic cyanobacteria on fish., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Available treatments against human fungal pathogens present high levels of resistance, motivating the development of new antifungal therapies. In this context, the present work aimed to analyze direct electric current (DC) antifungal action, using an in vitro apparatus equipped with platinum electrodes. Candida albicans yeast cells were submitted to three distinct conditions of DC treatment (anodic flow-AF; electroionic flow-EIF; and cathodic flow-CF), as well as different charges, ranging from 0.03 to 2.40 C. Our results indicated C. albicans presented distinct sensibility depending on the DC intensity and polarity applied. Both the colony-forming unit assay and the cytometry flow with propidium iodide indicated a drastic reduction on cellular viability after AF treatment with 0.15 C, while CF- and EIF-treated cells stayed alive when DC doses were increased up to 2.40 C. Additionally, transmission electron microscopy revealed important ultrastructural alterations in AF-treated yeasts, including cell structure disorganization, ruptures in plasmatic membrane, and cytoplasmic rarefaction. This work emphasizes the importance of physical parameters (polarity and doses) in cellular damage, and brings new evidence for using electrotherapy to treat C. albicans pathology process. Bioelectromagnetics. 38:95-108, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Purpose: Early diagnosis of gastric cancer is still the exception in Western countries. In the East, as in Japan and Korea, this disease is an endemic disorder. More conservative surgical procedures are frequently performed in early gastric cancer cases in these countries where sentinel lymph node navigation surgery is becoming a safe option for some patients. This study aims to evaluate preliminary outcomes of patients with early gastric cancer who underwent sentinel node navigation surgeries in Brazil, a country with non-endemic gastric cancer levels., Materials and Methods: From September 2008 to March 2014, 14 out of 205 gastric cancer patients underwent sentinel lymph node navigation surgeries, which were performed using intraoperative, endoscopic, and peritumoral injection of patent blue dye., Results: Antrectomies with Billroth I gastroduodenostomies were performed in seven patients with distal tumors. The other seven patients underwent wedge resections. Sentinel basin resections were performed in four patients, and lymphadenectomies were extended to stations 7, 8, and 9 in the other 10. Two patients received false-negative results from sentinel node biopsies, and one of those patients had micrometastasis. There was one postoperative death from liver failure in a cirrhotic patient. Another cirrhotic patient died after two years without recurrence of gastric cancer, also from liver failure. All other patients were followed-up for 13 to 79 months with no evidence of recurrence., Conclusions: Sentinel lymph node navigation surgery appears to be a safe procedure in a country with non-endemic levels of gastric cancer.

The purpose of this systematic review was to evaluate clinical studies on the follow-up survival of implants inserted in the zygomatic bone for maxillary rehabilitation. A comprehensive search of studies published from 2000 to July 2012 and listed in the PubMed/MEDLINE, Embase, and Cochrane Library databases was performed in accordance with the PRISMA statement. Relevant studies were selected according to predetermined inclusion and exclusion criteria. The initial database search yielded 751 titles. After filtering, 313 abstracts were selected, culminating in 42 full text articles. Application of eligibility criteria led to the elimination of 17 articles. Hence 25 full-text articles were considered clinically relevant and were included. Calculations of the interval survival rates and cumulative survival rates of implants could be carried out on the data extracted from the final list of included studies for the different time intervals. These studies reported the insertion of a total of 1541 zygomatic implants and 33 implant failures. Failure generally occurred during the first year interval and was related to clinical complications, such as recurrent acute and chronic sinusitis. After a 36-month follow-up, the survival rate was 97.86%. Additional studies with longer follow-up periods, including the number of zygomatic implants inserted and details of the variations in the surgical techniques used and the impact of the maxillary morphology are still required., (Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Three new sequences of Mitochondrial cytochrome c-oxidase subunit 2 (mtDNA cox-2) from C. pelagicum parasite of Spheniscus magellanicus, the Magelanicus penguin, were determined from Brazilian waters. The sequences presented 99 and 98% of similarity with C. pelagicum sequences from Argentina, deposited on GenBank for the same genetic region and with a strong statistical support inferred from the phylogenetic tree. The morphological and ultrastructural studies that were carried out confirmed the genetic analysis.

Objective: to evaluate the incidence of lymph node metastasis in early gastric cancer, identifying risk factors for its development., Methods: we conducted a prospective study of patients with gastric cancer admitted to the Section of the Esophago-Gastric Surgery of the Surgery of Service HUCFF-UFRJ, from January 2006 to May 2012., Results: the rate of early gastric cancer was 16.3%. The incidence of nodal metastases was 30.8% and occurred more frequently in patients with tumors with involvement of the submucosa (42.9%), in those poorly differentiated (36.4%), in tumors larger than 2 cm (33.3%) and in type III ulcerated lesions (43.8%)., Conclusion: the incidence of lymph node metastases in patients was very high and suggests that one should keep the radicality of resection in early gastric cancer, particularly in relation to D2 lymphadenectomy, recommended for advanced gastric cancer. Conservative resections, with lymphadenectomies smaller than D2, should be performed only in selected cases, well-studied as for the risk factors of lymph node metastasis. Despite the small number of cases did not permit to relate the rate of lymph node metastasis to the risk factors considered, we noted a strong tendency for the occurrence of these metastases in the poorly differentiated, type III, larger than 2 cm tumors, and in the Lauren diffuse types.

Background: Melanoides tuberculatus (Müller, 1774) (Thiaridae), an introduced gastropod mollusc with a wide geographical distribution in the Neotropics, is the intermediate host of the trematode Centrocestus formosanus (Nishigori, 1924) (Heterophyidae). This parasite is considered to be pathogenic to humans. The aim of the present work was to evaluate the locomotory activity of uninfected M. tuberculatus compared with those naturally infected with C. formosanus., Findings: The locomotory activity of each mollusc was recorded using an image analysis biomonitoring system, Videomex-V, to evaluate and quantify the parameters of 'Stereotypic' and 'Resting time'. The Generalized Estimating Equation analysis of locomotory activity of M. tuberculatus infected with C. formosanus revealed significant differences compared with uninfected molluscs for the parameters 'Stereotypic time' and 'Resting time' with a reduction of movement. The variations in the values of the monitoring intervals recorded showed a significant difference for the infected molluscs in the case of Stereotypic time, with an irregular locomotory activity pattern, as compared to that of uninfected molluscs. The analysis of the standard length of all molluscs did not exhibit any correlation with locomotory activity, showing that C. formosanus is able to alter the locomotory activity of its snail host regardless of the standard length., Conclusions: The trematode C. formosanus affects the locomotory activity of the mollusc M. tuberculatus by reducing its movement and causing it to exhibit an irregular pattern of activity, both of which are independent of the snail's standard length.

Owing to the veterinary and medical importance of heterophyid trematodes, a survey on Ascocotyle (Phagicola) longa in different organs of mullets Mugil liza from Rio de Janeiro was undertaken. The prevalence of metacercariae varied greatly between different organs of the mullets: spleen (100%), heart (98%), intestine wall (97%), liver (97%), muscle (87%), stomach wall (77%), brain (47%), gonads (30%) and gall bladder (30%). The high level of the intensity of the infection in relation to different fish organs was confirmed in two experimental infections performed during the spring/summer and autumn/winter seasons when 258 and 47 adult parasites were recovered from hamsters fed only with small pieces of muscle tissue. The potential risk of infection was considered to be high in view of the high prevalence and intensity of A. (P.) longa in the muscles of mullets throughout the year. Additionally new confocal imaging of metacercariae and adults experimentally obtained, enabled for the first time the description of a short genital atrium formed by the union of uterus and ejaculatory duct., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The aim of this study was to assess the improvement in psychosocial awareness of anophthalmic patients wearing ocular prostheses and its relationship with demographic characteristics, factors of loss/treatment, social activity, and relationship between professional and patient. Surveys including a form for evaluation of psychosocial pattern were conducted with 40 anophthalmic patients rehabilitated with ocular prosthesis at the Center of Oral Oncology in the authors' dental school from January 1998 to November 2010. The improvement in psychosocial awareness was assessed by comparing the perception of some feelings reported in the period of eye loss and currently. Wilcoxon tests were applied for comparison of patients' perception between the periods. χ(2) tests were used to assess the relationship between the improvement in psychosocial awareness and the variables of the study. In addition, the logistic regression model measured this relationship with the measure of odds ratio. The feelings of shame, shyness, preoccupation with hiding it, sadness, insecurity and fear were significant for improvement in psychosocial awareness. It was concluded that the anophthalmic patients wearing an ocular prosthesis has significant improvement in psychosocial awareness after rehabilitation., (Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: To study the sentinel lymph node in early gastric cancer as a diagnostic method of unsuspected lymph node metastasis, which may allow the performance, in those with negative lymph nodes, of smaller gastric resections with limited lymphadenectomy., Methods: We studied seven patients with early gastric cancer treated at the Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, from September 2008 to May 2011, who underwent sentinel lymph node exams, performed by intraoperative peritumoral endoscopic injection of patent blue dye., Results: We found an average of three sentinel nodes per patient. The frozen biopsy of lymph nodes was negative for metastases, which allowed the realization of atypical gastric resection in three cases and antrectomy with BI reconstruction in four. The performed lymphadenectomy was modified D1. There was no operative mortality. The duration of postoperative follow-up ranged from five to 37 months, without evidence of recurrence. One patient developed a second early tumor 13 months after the initial surgery and underwent total gastrectomy., Conclusion: The sentinel lymph node in early gastric cancer proved to be an effective method for the evaluation of nodal metastases in seven patients and allowed for smaller gastric resections and limited lymphadenectomies. These minor procedures reduce the risk of postoperative complications, maintaining, on the other hand, the oncological radicality that is required in the treatment of gastric cancer.

Satanoperca jurupari (Osteichthyes: Cichlidae) is reported for the first time to be parasitized by the nematodes Procamallanus (Spirocamallanus) rarus Travassos, Artigas and Pereira, 1928, Procamallanus (Spirocamallanus) sp., larvae of Raphidascaroides sp. and Anisakidae gen. sp., and by the acanthocephalan Neoechinorhynchus (Neoechinorhynchus) paraguayensis Machado Filho (Rev Bras Biol 19:379-381, 1959).

Raphidascaris (Sprentascaris) lanfrediae sp. nov. is described from the intestine of the freshwater fish Satanoperca jurupari (Heckel) (Cichlidae) from the Guamá River, state of Pará, Brazil. The prevalence in fish (n = 59) was 27% with intensity of one-124 (mean 16) nematodes per fish. The new species is characterized mainly by the markedly larger size of ventricular appendix in relation to the oesophagus, presence of short male caudal alae, 14-16 subventral pairs of preanal papillae and six pairs of postanal papillae.

The authors present the current view of the women in Surgery since the end of the XIX century until now. They discuss the difficulties they face when they choose Surgery as a career and the progress now achieved.

The author presents the Residency in General Surgery in Brazil from its inception, outlining its changes up to the present day. She discusses her doubts and thoughts about the best model for General Surgery residency programs and the declining demand for General Surgery as a career and the causes for such decline.

In the district of Paracambi, State of Rio de Janeiro an epidemiological survey for American tegumentary leishmaniasis in canine population was carried out in endemic localities. A total of 179 dogs was registered and 138 (77.1%) examined for their clinical aspects, development of delayed hypersensitivity (DHS) with Imunoleish(R) antigen and serological responses by indirect immunofluorescent reaction and enzyme-linked immunosorbent assay. In 9 (6.5%) dogs with active cutaneous lesions or suspect scars, 66.7% were caused by Leishmania sp; 44.4% produced infection in hamsters and showed growth in culture media, which was considered to be compatible with the species of Leishmania braziliensis complex. The molecular characterization (isoenzyme and KDNA restriction profiles) defined two strains with similar profiles for L. (Viannia) braziliensis. The prevalence of canine infection estimated by the cutaneous test, IFR and ELISA was 10.1%, 16.7% and 27.8%, respectively. The presence of clinical / sub-clinical form of ATL in canine population associated with human infections suggested that the dog can act as source of infection as well as for dissemination of the disease.

In some tissues, rapid effects of estrogens have been described at the plasma membrane level including activation of the MAPK activity. In rat adipocytes, the present study demonstrates that physiological concentrations (0.1-10 nM) of E2 rapidly activate the p42/p44 MAPK. This effect was blocked by the pure estrogen antagonist, ICI 182 780, and appeared specific for E2 because 17alpha-E2, T, and progesterone failed to change the MAPK activity. Pertussis toxin; PP2, a selective inhibitor of Src family kinase; and wortmannin all reduced the magnitude of MAPK activation by E2 suggesting involvement of the Gi-protein/Src family kinase/PI3K pathway. Classical PKCs and MAPK kinase were also involved in MAPK activation by E2. Interestingly, this activation was observed in late but not early differentiated rat preadipocytes, and the immunoreactive ER(alpha) protein was detected only in adipocyte membrane, suggesting that the adipocyte membrane structure is required for the nongenomic effect of E2. Moreover, E2 induced a rapid nuclear translocation of MAPK together with a fast MAPK- dependent activation of cAMP response element binding protein leading to a transcriptional activation of cAMP response element binding protein-responsive genes and reported plasmids. However, the E2 increase in adipocyte activator protein-1 DNA binding does not seem to be fully explained by the E2 activation of the MAPK pathway. This study provides clear evidence for an additional nongenomic mechanism whereby estrogens may exert their control on adipose tissue metabolism.