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Cancer therapy is facing increasingly significant challenges, marked by a wide range of techniques and research efforts centered around somatic mutations, precision oncology, and the vast amount of big data. Despite this abundance of information, the quest to cure cancer often seems more elusive, with the "war on cancer" yet to deliver a definitive victory. A particularly pressing issue is the development of tumor treatment resistance, highlighting the urgent need for innovative approaches. Evolutionary, Quantum Biology and System Biology offer a promising framework for advancing experimental cancer research. By integrating theoretical studies, translational methods, and flexible multidisciplinary clinical research, there's potential to enhance current treatment strategies and improve outcomes for cancer patients. Establishing stronger links between evolutionary, quantum, entropy and chaos principles and oncology could lead to more effective treatments that leverage an understanding of the tumor's evolutionary dynamics, paving the way for novel methods to control and mitigate cancer. Achieving these objectives necessitates a commitment to multidisciplinary and interprofessional collaboration at the heart of both research and clinical endeavors in oncology. This entails dismantling silos between disciplines, encouraging open communication and data sharing, and integrating diverse viewpoints and expertise from the outset of research projects. Being receptive to new scientific discoveries and responsive to how patients react to treatments is also crucial. Such strategies are key to keeping the field of oncology at the forefront of effective cancer management, ensuring patients receive the most personalized and effective care. Ultimately, this approach aims to push the boundaries of cancer understanding, treating it as a manageable chronic condition, aiming to extend life expectancy and enhance patient quality of life., Competing Interests: Author MVPdS was employed by company Tergos Pesquisa E Ensino S.A. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Casotti, Meira, Zetum, Campanharo, Silva, Giacinti, Silva, Moura, Barbosa, Altoé, Mauricio, Góes, Alves, Linhares, Ventorim, Guaitolini, Santos, Errera, Groisman, Carvalho, Paula, Sousa, Fechine and Louro.)

Pesticide exposure is a risk factor for the development of several diseases, including breast cancer (BC). The enzyme UGT2B7 participate in detoxification of pesticides and the presence rs7438135 (G > A) variant in your gene increases its glucuronidation potential, contributing to oxidative stress metabolites neutralization. Here we investigated the impact of occupational pesticide exposure on the systemic oxidative stress generation from 228 women with BC depending on their UGT2B7 rs7438135 (G > A) status. q-PCR investigated the presence of the rs7438135 variant, and oxidative stress markers (lipid peroxidation levels, total antioxidant capacity-TRAP, and nitric oxide metabolites-NOx) were measured in plasma. Pesticide exposure induced significant augment in the systemic lipid peroxidation in the presence of the variant for several clinicopathological conditions, including tumors with high proliferation index (ki67) and with high aggressiveness. NOx was augmented in high ki67, positive progesterone receptors, high-grade and triple-negative/Luminal B tumors, and low-risk stratified patients. TRAP was depleted in young patients at menopause and those with triple-negative/Luminal B tumors, as well as those stratified as at low risk for death and recurrence. These findings showed that the presence of the variant was not able to protect from pesticide-induced oxidative stress generation in BC patients., (© 2024 Wiley Periodicals LLC.)

Objective: To determine the prevalence of anxiety, depression and burnout in residents of Gynecology and Obstetrics during COVID-19 pandemic in Brazil and its associated factors., Methods: Cross-sectional study involving all regions of Brazil, through the application of a sociodemographic questionnaire, the Hospital Anxiety and Depression Scale (HAD) and the Maslach Burnout Inventory (MBI-HSS) instrument. Multivariate analysis was performed after adjusting the Poisson model., Results: Among the 719 participating medical residents, screening was positive for anxiety in 75.7% and for depression in 49.8% of cases. Burnout syndrome was evidenced in 41.3% of the physicians studied. Those with depression are more likely to have anxiety (OR 0.797; 95%CI 0.687 - 0.925) and burnout syndrome (OR 0.847 95%CI 0.74 - 0.97). Residents with anxiety (OR 0.805; 95%CI 0.699 - 0.928) and burnout (OR 0.841; 95%CI 0.734 - 0.963) are more likely to have depression., Conclusion: High prevalence of anxiety, depression and burnout were found in residents of Gynecology and Obstetrics in Brazil, in addition to important correlations between anxiety-depression and depression-burnout., Competing Interests: Conflicts to interest: none to declare., (© 2024. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved.)

Lannea L. genus belongs to the Anacardiaceae botanical family and has long been used in traditional medicinal systems of many countries to manage several health conditions, but no studies have been conducted regarding its usefulness as a source of herbal medicine for human use. A literature review was conducted on scientific papers indexed on B-On, Pubmed, and Web of Science databases. Our results showed that medicinal plants from this botanical genus, mostly constituted by bark and leaf, are often used to approach a wide variety of disease symptoms, like fever, inflammatory states, pain, and gastrointestinal disorders. Phytochemical profiles of Lannea species revealed that phenolic acid derivatives including hydroquinones, phenolic acids, flavonoids, condensed tannins, and triterpenoids are the main classes of secondary metabolites present. Among the total of 165 identified compounds, 57 (34.5%) are flavonoids, mostly quercetin- and myricetin-derived flavonols and catechin and epicatechin flavan-3-ol derivatives also containing a galloyl group. In vitro and in vivo studies allowed the identification of 12 different biological activities, amongst which antimicrobial, antioxidant, anti-inflammatory, and cytotoxic activities were the most frequently cited and observed in in vitro essays. Our review contributes useful information for the scientifical validation of the use of Lannea species in traditional medicinal systems and shows that more research needs to be conducted to better understand the concrete utility of these as herbal medicines.

Importance: Bothrops venom acts almost immediately at the bite site and causes tissue damage., Objective: To investigate the feasibility and explore the safety and efficacy of low-level laser therapy (LLLT) in reducing the local manifestations of B atrox envenomations., Design, Setting, and Participants: This was a double-blind randomized clinical trial conducted at Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, in Manaus, Brazil. A total of 60 adult participants were included from November 2020 to March 2022, with 30 in each group. Baseline characteristics on admission were similarly distributed between groups. Data analysis was performed from August to December 2022., Intervention: The intervention group received LLLT combined with regular antivenom treatment. The laser used was a gallium arsenide laser with 4 infrared laser emitters and 4 red laser emitters, 4 J/cm2 for 40 seconds at each application point., Main Outcomes and Measures: Feasibility was assessed by eligibility, recruitment, and retention rates; protocol fidelity; and patients' acceptability. The primary efficacy outcome of this study was myolysis estimated by the value of creatine kinase (U/L) on the third day of follow-up. Secondary efficacy outcomes were (1) pain intensity, (2) circumference measurement ratio, (3) extent of edema, (4) difference between the bite site temperature and that of the contralateral limb, (5) need for the use of analgesics, (6) frequency of secondary infections, and (7) necrosis. These outcomes were measured 48 hours after admission. Disability assessment was carried out from 4 to 6 months after patients' discharge. P values for outcomes were adjusted with Bonferroni correction., Results: A total of 60 patients (mean [SD] age, 43.2 [15.3] years; 8 female individuals [13%] and 52 male individuals [87%]) were included. The study was feasible, and patient retention and acceptability were high. Creatine kinase was significantly lower in the LLLT group (mean [SD], 163.7 [160.0] U/L) 48 hours after admission in relation to the comparator (412.4 [441.3] U/L) (P = .03). Mean (SD) pain intensity (2.9 [2.7] vs 5.0 [2.4]; P = .004), circumference measurement ratio (6.6% [6.6%] vs 17.1% [11.6%]; P < .001), and edema extent (25.8 [15.0] vs 40.1 [22.7] cm; P = .002) were significantly lower in the LLLT group in relation to the comparator. No difference was observed between the groups regarding the mean difference between the bite site temperature and the contralateral limb. Secondary infections, necrosis, disability outcomes, and the frequency of need for analgesics were similar in both groups. No adverse event was observed., Conclusions and Relevance: The data from this randomized clinical trial suggest that the use of LLLT was feasible and safe in a hospital setting and effective in reducing muscle damage and the local inflammatory process caused by B atrox envenomations., Trial Registration: Brazilian Registry of Clinical Trials Identifier: RBR-4qw4vf.

Previously, it was suggested that biological maturation (BM) could be linked to cardiac autonomic recovery (CAR) in the pediatric population. However, this influence hasn't been confirmed yet. Our aim was to investigate the impact of BM on CAR in female volleyball players. Experimental study with a sample of 38 volleyball players, comprising 20 girls (age: [11.6 ​± ​2.1] years) and 18 women (age: [24.5 ​± ​5.5] years), we analyzed BM, comparing maturing subjects (girls) with mature subjects (women). Additionally, we assessed peak height velocity (PHV) in girls. We conducted a training session involving repeated sprints (3 rounds of 6 sprints interspersed by 5 ​min [min] of passive rest). Using short-range radio telemetry, we analyzed CAR during (at the end of the 1 st and 2 nd rounds) and after (following the 3 rd round) the training session of repeated sprints by applying the 60-s to 300-s heart rate recovery index (HRR-Index). Girls exhibited superior CAR compared to women (round 2: 60-s, 120-s, 240-s, and 300-s, p  ​< ​0.005). Subgroup analyses of BM indicated that individuals in the Late-PHV stage demonstrated superior CAR compared to those in the Early-PHV and During-PHV groups. (60-s to 300-s, η 2 p  ​> ​0.4, p  ​< ​0.05). Subjects in the During-PHV stage were superior to those in the Early-PHV stage (240-s á 300-s, η 2 p  ​> ​0.4, p  ​< ​0.05). We have concluded that biological maturation has a significant impact on cardiac autonomic recovery., Competing Interests: 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., (© 2023 Chengdu Sport University. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Root tubers of Asphodelus bento-rainhae subsp. bento-rainhae (AbR), a vulnerable endemic species, and Asphodelus macrocarpus subsp. macrocarpus (AmR) have traditionally been used in Portugal to treat inflammatory and infectious skin disorders. The present study aims to evaluate the in vitro antimicrobial activity of crude 70% and 96% hydroethanolic extracts of both medicinal plants, specifically against multidrug-resistant skin-related pathogens, to identify the involved marker secondary metabolites and also to assess the pre-clinical toxicity of these medicinal plant extracts. Bioguided fractionation of the 70% hydroethanolic extracts of both species using solvents of increasing polarity, namely diethyl ether (DEE: AbR-1, AmR-1), ethyl acetate (AbR-2, AmR-2) and aqueous (AbR-3, AmR-3) fractions, enabled the identification of the DEE fractions as the most active against all the tested Gram-positive microorganisms (MIC: 16 to 1000 µg/mL). Furthermore, phytochemical analyses using TLC and LC-UV/DAD-ESI/MS techniques revealed the presence of anthracene derivatives as the main constituents of DEE fractions, and five known compounds, namely 7'-(chrysophanol-4-yl)-chrysophanol-10'- C -beta- D -xylopyranosyl-anthrone ( p ), 10,7'-bichrysophanol ( q ), chrysophanol ( r ), 10-(chrysophanol-7'-yl)-10-hydroxychrysophanol-9-anthrone ( s ) and asphodelin ( t ) , were identified as the main marker compounds. All these compounds showed high antimicrobial activity, particularly against Staphylococcus epidermidis (MIC: 3.2 to 100 µg/mL). Importantly, no cytotoxicity against HepG2 and HaCaT cells (up to 125 µg/mL) for crude extracts of both species and genotoxicity (up to 5000 µg/mL, with and without metabolic activation) for AbR 96% hydroethanolic extract was detected using the MTT and Ames tests, respectively. Overall, the obtained results contribute to the concrete validation of the use of these medicinal plants as potential sources of antimicrobial agents in the treatment of skin diseases.

Background: Pit viper snakebites are challenging as they often cause tissue injury and secondary bacterial infection that may impair full recovery of the affected limb. We describe the evolution of a snakebite injury with secondary infection and the use of specialized dressings to achieve tissue repair and complete closure of the wound., Case: Ms E., a 45-year-old woman, was bitten by a pit viper that began as a small lesion and progressed to necrosis, cellulitis, edema, and hyperemia of the perilesional skin, local inflammation, and infection. We implemented a combination of topical hydrogel therapy with calcium alginate and hydrofiber with 1.2% silver to promote autolytic debridement, combat local infection, and provide a moist wound environment. The wound required daily local treatment for 2 months due to extensive tissue damage, combined with the proteolytic action of the bothropic venom., Conclusion: The care of wounds caused by snakebites is a challenge for the health care team due to tissue loss resulting from the action of the venom and secondary bacterial infection. Close follow-up with the use of systemic antibiotics and topical therapies proved effective in minimizing tissue loss in this case., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 by the Wound, Ostomy and Continence Nurses Society.)

The physiological expression of HLA-G is mainly observed in the placenta, playing an essential role in maternal-fetal tolerance. Among the HLA-G mRNA alternative transcripts, the one lacking 92 bases at the HLA-G 3' untranslated region (3'UTR), the 92bDel transcript, is more stable, is associated with increased HLA-G soluble levels, and was observed in individuals presenting a 14 bp insertion (14 bp + ) at the 3'UTR. We investigated the presence of the 92bDel transcript in placenta samples, correlating its expression levels with the HLA-G polymorphisms at the 3'UTR. The 14 bp + allele correlates with the presence of the 92bDel transcript. However, the polymorphism triggering this alternative splicing is the + 3010/C allele (rs1710, allele C). Most 14 bp + haplotypes (UTR-2/-5/-7) present allele + 3010/C. However, 14 bp - haplotypes such as UTR-3 are also associated with + 3010/C, and the 92bDel transcript can be detected in homozygous samples for the 14 bp- allele carrying at least one copy of UTR-3. The UTR-3 haplotype is associated with alleles G*01:04 and the HLA-G lineage HG0104, which is a high-expressing lineage. The only HLA-G lineage that is not likely to produce this transcript is HG010101, associated with the + 3010/G allele. This functional difference may be advantageous, considering the high worldwide frequency of the HG010101 lineage. Therefore, HLA-G lineages are functionally distinct regarding the 92bDel transcript expression, and the 3010/C allele triggers the alternative splicing that produces this shorter and more stable transcript., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Sepsis is a severe global health problem, with high morbidity and mortality. In sepsis, one of the main affected organs is the liver. Hepatic alterations characterize a negative prognostic. Omega-3 fatty acids (ω3), eicosapentaenoic acid, and docosahexaenoic acid, are part of the main families of polyunsaturated fatty acids. ω3 has been used in studies as sepsis treatment and as a treatment for non-alcoholic liver disease., Aim: We aimed to evaluate the effects of treatment with fish oil (FO) rich in ω3 on liver changes and damage resulting from experimental sepsis., Methodology: A model of severe sepsis in Wistar rats was used. Oxidative stress in the liver tissue was evaluated by means of tests of thiobarbituric acid reactive substances, 2,7-dihydrodichlorofluorescein diacetate , catalase, and glutathione peroxidase, in the serum TBARS, DCF, thiols and, to assess liver dysfunction, alanine aminotransferase and aspartate aminotransferase. Hepatic tissue damage was evaluated using H&E histology., Results: In assessments of oxidative stress in liver tissue, a protective effect was observed in the tests of TBARS, DCF, CAT, and GPx, when compared the sepsis versus sepsis+ω3 groups. Regarding the oxidative stress in serum, a protective effect of treatment with ω3 was observed in the TBARS, DCF, and thiols assays, in the comparison between the sepsis and sepsis+ω3 groups. ω3 had also a beneficial effect on biochemical parameters in serum in the analysis of ALT, creatinine, urea, and lactate, observed in the comparison between the sepsis and sepsis+ω3 groups., Conclusion: The results suggest ω3 as a liver protector during sepsis with an antioxidant effect, alleviating injuries and dysfunctions., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Dried leaves of Lannea velutina A. Rich. and Sorindeia juglandifolia (A. Rich.) Planch. ex Oliv. (family Anacardiaceae) are used in African traditional medicine. Although these medicinal plants have widespread use in the treatment of inflammatory diseases, there is no scientific data concerning their preclinical or clinical safety. This work aimed to investigate the phytochemical properties of the leaves of both species using HPLC-UV/DAD, as well as the in vivo oral repeated-dose toxicity of 70% hydroethanolic leaf extract of S. juglandifolia and the in vitro genotoxicity of 70% hydroethanolic leaf extracts of L. velutina and S. juglandifolia . Clinical signs of toxicity, body weight variations, and changes in food consumption, mortality, and blood biochemical parameters were monitored. Genotoxicity was assessed using the bacterial reverse mutation assay (Ames test) with and without metabolic activation, according to OECD guidelines. The obtained results showed the presence of gallic acid and anacardic acid as the main marker constituents in both species. No significant changes in general body weight or food intake were observed; small significant changes with no critical relevance were observed in the blood biochemistry of animals treated with S. juglandifolia hydroethanolic extract (50, 400, and 1000 mg/kg body weight) compared to those in the control group. No genotoxicity was observed in the bacterial reverse mutation assay with S. juglandifolia and L. velutina extracts (up to 5 mg/plate). The safety data obtained in vivo and lack of genotoxic potential in vitro points to the safe medicinal use of S. juglandifolia and L. velutina extracts.

Ozone (O 3 ) represents a great threat to human health, contributing to respiratory diseases and premature mortality. This pollutant is often considered a critical pollutant in regions of southern Brazil. Exposure to this pollutant during vigorous physical activity should be the subject of thorough investigations due to the increased ventilation rate and altered breathing pattern present during vigorous physical activity that result in greater inhalation of O 3 . Thus, this study aimed to evaluate the health risk of exposure to low, mean, and high concentrations of O 3 during different durations of exercise in the city of Rio Grande (southern Brazil). Healthy young men (n = 45) performed cardiopulmonary exercise testing, and ventilation rate data were collected to predict total ventilation and pollutant inhalation during a 5 km running session. The O 3 concentration in the city of Rio Grande was obtained from data reported by the Copernicus Atmosphere Monitoring Service (CAMS). The environmental health risk was calculated based on the potential intake dose. The lowest, mean, and highest concentrations of O 3 detected during the monitoring period were 32.5, 64.9, and 115.2 µg/m 3 , respectively. In all evaluated scenarios, there was a toxicological risk (RQ > 1), except when exercising when the O 3 concentration was lowest for the shortest length of time (p < 0.001). As the concentration of O 3 and the duration of the exposure increase, the health risk is increased. Therefore, O 3 concentration and duration of exposure are factors influencing the health risk of exercising. These findings are extremely relevant in cities that have high levels of O 3 , such as the city of Rio Grande., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Purinergic signaling modulates immune function and is involved in the immunopathogenesis of several viral infections. This study aimed to investigate alterations in purinergic pathways in coronavirus disease 2019 (COVID-19) patients. Mild and severe COVID-19 patients had lower extracellular adenosine triphosphate and adenosine levels, and higher cytokines than healthy controls. Mild COVID-19 patients presented lower frequencies of CD4 + CD25 + CD39 + (activated/memory regulatory T cell [mTreg]) and increased frequencies of high-differentiated (CD27 - CD28 - ) CD8 + T cells compared with healthy controls. Severe COVID-19 patients also showed higher frequencies of CD4 + CD39 + , CD4 + CD25 - CD39 + (memory T effector cell), and high-differentiated CD8 + T cells (CD27 - CD28 - ), and diminished frequencies of CD4 + CD73 + , CD4 + CD25 + CD39 + mTreg cell, CD8 + CD73 + , and low-differentiated CD8 + T cells (CD27 + CD28 + ) in the blood in relation to mild COVID-19 patients and controls. Moreover, severe COVID-19 patients presented higher expression of PD-1 on low-differentiated CD8 + T cells. Both severe and mild COVID-19 patients presented higher frequencies of CD4 + Annexin-V + and CD8 + Annexin-V + T cells, indicating increased T-cell apoptosis. Plasma samples collected from severe COVID-19 patients were able to decrease the expression of CD73 on CD4 + and CD8 + T cells of a healthy donor. Interestingly, the in vitro incubation of peripheral blood mononuclear cell from severe COVID-19 patients with adenosine reduced the nuclear factor-κB activation in T cells and monocytes. Together, these data add new knowledge to the COVID-19 immunopathology through purinergic regulation., (© 2022 Wiley Periodicals LLC.)

High-throughput DNA sequencing has allowed for the identification of genomic alterations and their impact on tumor development, progression, and therapeutic responses. In PSCC, for which the incidence has progressively increased worldwide, there are still limited data on the molecular mechanisms involved in the disease pathogenesis. In this study, we characterized the mutational signature of 30 human papillomavirus (HPV)-associated PSCC cases from Latin Americans, using whole-exome sequencing. Copy number variations (CNVs) were also identified and compared to previous array-generated data. Enrichment analyses were performed to reveal disrupted pathways and to identify alterations mapped to HPV integration sites (HPVis) and miRNA-mRNA hybridization regions. Among the most frequently mutated genes were NOTCH1 , TERT , TTN , FAT1 , TP53 , CDKN2A , RYR2 , CASP8 , FBXW7 , HMCN2 , and ITGA8 . Of note, 92% of these altered genes were localized at HPVis. We also found mutations in ten novel genes ( KMT2C , SMARCA4 , PTPRB , AJUBA , CR1 , KMT2D , NBEA , FAM135B , GTF2I , and CIC ), thus increasing our understanding of the potential HPV-disrupted pathways. Therefore, our study reveals innovative targets with potential therapeutic benefits for HPV-associated PSCCs. The CNV analysis by sequencing (CNV-seq) revealed five cancer-associated genes as the most frequent with gains ( NOTCH1 , MYC , NUMA1 , PLAG1 , and RAD21 ), while 30% of the tumors showed SMARCA4 with loss. Additionally, four cancer-associated genes ( CARD11 , CSMD3 , KDR , and TLX3 ) carried untranslated regions (UTRs) variants, which may impact gene regulation by affecting the miRNAs hybridization regions. Altogether, these data contribute to the characterization of the mutational spectrum and its impact on cellular signaling pathways in PSCC, thus reinforcing the pivotal role of HPV infection in the molecular pathogenesis of these tumors.

Objective: To verify the validity in the internal consistency in the spectrographic analysis protocol (SAP)., Material and Methods: Thirty-nine students of the Speech-Language Pathology graduate program and 38 speech-language pathologists, specialized in voice, participated in the study. The participants made visual inspections of 10 spectrograms and marked the items of the SAP. For analysis of the internal consistency in the SAP, the exploratory factor analysis (EFA) and confirmatory factor analysis were performed., Results: Most items showed corrected item-total correlation above 0.3, indicating that the items have a good relationship with each other and with the SAP as a whole. Six items presented values below the average, suggesting the exclusion of these from the construct. However, three of these were maintained because they were judged as important parameters in clinical practice, requiring the training of judges when using the SAP to properly understand the items. The EFA regrouped the previous domains of the SAP into three factors. All items presented a factor load above 0.4, suggesting the retention of all, except for the items previously indicated, for exclusion. The confirmatory factor analysis corroborated with the EFA and its indexes., Conclusion: The SAP has good internal consistency. All items have a good degree of relationship with each other and contribute positively to the protocol as a whole. The final version of the SAP, at this stage, has 15 items (from the 25 items of the initial SAP version), distributed among three domains., (Copyright © 2020 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

The thiazolidinone ring is found in compounds that have widespan biology activity and there is mechanism-based evidence that compounds bearing this moiety inhibit P. aeruginosa PhzS ( Pa PzhS), a key enzyme in the biosynthesis of the virulence factor named pyocyanin. Ten novel thiazolidinone derivatives were synthesised and screened against Pa PhzS, using two orthogonal assays. The biological results provided by these and 28 other compounds, whose synthesis had been described, suggest that the dihydroquinazoline ring, found in the previous hit ( A - Kd = 18 µM and LE = 0.20), is not required for Pa PzhS inhibition, but unsubstituted nitrogen at the thiazolidinone ring is. The molecular simplification approach, pursued in this work, afforded an optimised lead compound ( 13 - 5-(2,4-dimethoxyphenyl)thiazolidine-2,4-dione) with 10-fold improvement in affinity (Kd= 1.68 µM) and more than 100% increase in LE (0.45), which follows the same inhibition mode as the original hit compound (competitive to NADH).Executive summaryPhzS is a key enzyme in the pyocyanin biosynthesis pathway in P. aeruginosa. Orthogonal assays (TSA and FITC) show that fragment-like thiazolidinedione derivatives bind to Pa PhzS with one-digit micromolar affinity.Fragment-like thiazolidinedione derivatives bind to the cofactor (NADH) binding site in Pa PhzS.The molecular simplification optimised the ligand efficiency and affinity of the lead compound.

Mucosal barrier alterations may play a role in the pathogenesis of several diseases, including COVID-19. In this study we evaluate the association between bacterial translocation markers and systemic inflammation at the earliest time-point after hospitalization and at the last 72 h of hospitalization in survivors and non-survivors COVID-19 patients. Sixty-six SARS-CoV-2 RT-PCR positive patients and nine non-COVID-19 pneumonia controls were admitted in this study. Blood samples were collected at hospital admission (T1) (Controls and COVID-19 patients) and 0-72 h before hospital discharge (T2, alive or dead) to analyze systemic cytokines and chemokines, lipopolysaccharide (LPS) concentrations and soluble CD14 (sCD14) levels. THP-1 human monocytic cell line was incubated with plasma from survivors and non-survivors COVID-19 patients and their phenotype, activation status, TLR4, and chemokine receptors were analyzed by flow cytometry. COVID-19 patients presented higher IL-6, IFN-γ, TNF-α, TGF-β1, CCL2/MCP-1, CCL4/MIP-1β, and CCL5/RANTES levels than controls. Moreover, LPS and sCD14 were higher at hospital admission in SARS-CoV-2-infected patients. Non-survivors COVID-19 patients had increased LPS levels concomitant with higher IL-6, TNF-α, CCL2/MCP-1, and CCL5/RANTES levels at T2. Increased expression of CD16 and CCR5 were identified in THP-1 cells incubated with the plasma of survivor patients obtained at T2. The incubation of THP-1 with T2 plasma of non-survivors COVID-19 leads to higher TLR4, CCR2, CCR5, CCR7, and CD69 expression. In conclusion, the coexistence of increased microbial translocation and hyperinflammation in patients with severe COVID-19 may lead to higher monocyte activation, which may be associated with worsening outcomes, such as death., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Management of patient flow within a healthcare network, allowing equitable and qualified access to healthcare, is a major challenge for universal health systems. Implementation of telehealth strategies to support referral management has been shown to increase primary care resolution and to promote coordination of care. The objective of this study was to assess the impact of telehealth strategies on waiting lists and waiting times for specialized care in Brazil., Methods: Before-and-after study with measures obtained between January 2019 and February 2020. Baseline measurements of waiting lists were obtained immediately before the implementation of a remotely operated referral management system. Post-interventional measurements were obtained monthly, up to six months after the beginning of operation. Data was extracted from the database of the project. General linear models were applied to assess interaction of locality and time over number of cases on waiting lists and waiting times., Results: At baseline, the median number of cases on waiting lists ranged from 2961 to 12,305 cases. Reductions of the number of cases on waiting lists after six months of operation were observed in all localities. The magnitude of the reduction ranged from 54.67 to 88.97 %. Interaction of time measurements was statistically significant from the second month onward. Median waiting times ranged from 159 to 241 days at baseline. After six months, there was a decrease of 100 and 114 waiting days in two localities, respectively, with reduction of waiting times only for high-risk cases in the third locality., Conclusions: Adoption of telehealth strategies resulted in the reduction of number of cases on waiting lists. Results were consistent across localities, suggesting that telehealth interventions are viable in diverse settings., (© 2021. The Author(s).)

The microlepidoptera, Bedellia somnulentella (Zeller), is an important pest of sweetpotato, Ipomoea batatas (L.) Lam. Damage by B. somnulentella occurs in the larval stage and when consuming the foliar mesophyll of I. batatas make the leaves brown, wrinkled, and reducing the photosynthetic area and the yield. The detection and management of this pest depends on knowing its biological cycle and identifying its natural enemies. The objectives of this study were to determine the life history of B. somnulentella feeding on I. batatas leaves and to survey parasitoids of this pest in the field. The duration and viability of B. somnulentella egg, larva, prepupa, pupa, and adult stages were evaluated under laboratory conditions. Cephalic capsule width was measured to determine the number of B. somnulentella instars, based on the Dyar rule and analyzed by the Akaike statistical model (AIC). The developmental period of B. somnulentella was 32.5 ± 0. 21 d with a viability of 75, 84, 100, and 84% for the egg, larva, prepupa, and pupa stages, respectively. The identification of this pest on the plants is possible from the third instar and in the pupal and adult stages. The parasitoid Conura sp. (Hymenoptera: Chalcididae) was identified parasitizing pupae of B. somnulentella and could be considered a potential natural enemy for the integrated management of this pest., (© The Author(s) 2021. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We evaluated the impact of maximal exercise on oxidative stress and DNA damage in peripheral blood mononuclear cells (PBMC) from sedentary and exercised lean and obese men. PBMC were collected before, immediately and 1-h after exercise and exposed to hydrogen peroxide (H 2 O 2 ; 25 and 50 µM, 4 h). A leukocytosis was induced by maximal exercise immediately and 1-h after exercise in all groups. However, a lymphopenia was observed 1-h after exercise in the Sedentary obese group. In the control condition, low DNA damage index concomitant to increases in intracellular glutathione content (GSH) was identified immediately after exercise in all groups. However, higher DNA damage index and lipid peroxidation occurred 1-h after the bout in Sedentary and Exercised Obese groups. PBMC exposed to both H 2 O 2 25 and 50 µM experienced higher DNA damage and lipid peroxidation index immediately after exercise in all groups. Both lipid peroxidation and DNA damage index remained higher in PBMC of Sedentary Lean, Sedentary Obese, and Exercised obese groups obtained 1-h after exercise in both H 2 O 2 25 and 50 µM, with the highest values identified in PBMC from Sedentary Obese group. However, increases in GSH content were identified in treated PBMC from sedentary and exercised lean groups as well as exercised obese group 1-h after exercise. Habitual exercise confers increased resistance of PBMC to DNA damage induced by oxidative stress, reducing the detrimental effects of obesity.Keywords: Exercise, physical activity, DNA damage, obesity, mutagenesis, oxidative stress.

A scoping review, based on the RE-AIM framework, was conducted to analyze evidence of reach, effectiveness, adoption, implementation, and maintenance of the Strengthening Families Program (10-14), a preventive family-based substance abuse program for adolescents. Sixty-five articles were included. The results disclosed that effectiveness, implementation, and maintenance at the individual-level were the most evaluated aspects, while reach, maintenance at the setting-level, and adoption were the least investigated aspects. Positive effects on drug abuse prevention and protective parenting factors were found in the U.S. studies. Likewise, Latin American studies have shown the improvement of parenting practices. However, European studies have produced mixed results, with predominantly null effects on substance abuse. The implementation quality was high. There is no available evidence of adoption and maintenance at the setting-level by the organizations that implemented it. New studies must examine the reach, adoption, and sustainability of the program to lay foundations for its future use as an instrument of public policies.

This study evaluated the effects of heat stress on the ex vivo inflammatory profile in untrained and trained men. Whole blood samples from untrained (UT) and trained (TR) individuals were incubated for 2 h at 37 °C or 40 °C. The whole blood of a subsample of the participants (n = 5 in both TR and UT groups) were stimulated with lipopolysaccharide (LPS, 10 ng/mL) concomitant to heat treatment (37 °C versus 40 °C). Flow cytometry was used to assess the intracellular NF-κB activation in CD4+ T cells and CD14+ monocytes, the expression of Toll-Like Receptor-4 (TLR-4), the frequencies of CD4+CD25-CD39+ and CD4+CD25+CD39+ T cells and monocyte subsets (CD14+CD16-; CD14+CD16+; CD14-CD16+), the mitochondrial membrane potential (MMP) and the reactive oxygen species (ROS) production by lymphocytes and monocytes. The production of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) by LPS-stimulated whole blood were also evaluated. Heat treatment (40 °C) increased the proportions of CD14+CD16- and CD14+CD16+ monocytes and the lymphocyte MMP in the UT group. The frequencies of CD14-CD16+ monocytes and the activation of NF-κB in CD14+ monocytes decreased in UT and TR groups after heat treatment, while a reduction in CD4+CD25-CD39+ T-cells was observed only in the UT group. Higher TLR-4 and NF-κB activation were found in LPS-stimulated monocytes of UT men concomitant with higher TNF-α production and diminished IL-10 production after heat treatment. TR individuals presented lower NF- κB activation in LPS-stimulated monocytes after heat treatment. Our data suggest that the training status of individuals may impact on the anti-inflammatory response of heat treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Few investigations have evaluated isokinetic torque after a period of weight loss in wrestlers. Thus, the current study sought to investigate the effects of gradual weight loss in the precompetitive period on isokinetic peak torque in the upper and lower limbs and body composition in wrestling athletes., Methods: Eight elite athletes participated in the study (mean age 20.8±3.1 years). The athletes visited the laboratory on 2 occasions: during the period of weight maintenance (baseline) and during weight loss, in the precompetitive period (post). The variables analyzed were body composition through air displacement plethysmography (BOD POD) and peak torque (PT) of knee flexion and extension movements, and internal and external shoulder rotation in concentric action, at speeds of 60°/s and 180°/s, determined using an isokinetic dynamometer (Biodex Medical Systems; Shirley, NY, USA)., Results: A significant decrease was observed in body composition values, except lean mass. No significant differences were observed in the PT of the movements analyzed: Shoulder internal rotation (60°/s P=0.825; 180°/s P=0.245) and external rotation (60°/s P=0.149; 180°/s P=0.163) and knee extension (60°/s P=0.086; 180°/s P=0.630) and flexion (60°/s P=0.310; 180°/s P=0.239)., Conclusions: Gradual weight loss did not affect the production of torque in the wrestlers before a competition. In addition, gradual weight loss contributed to a reduction in body fat, associated with an increase in percentage lean body mass.

In this study, we evaluated the effects of autologous serum collected after two types of exercise on the in vitro inflammatory profile and T cell phenotype of resting peripheral blood mononuclear cells (PBMCs) in obese men. Serum samples and PBMCs were obtained from eight obese men who performed two exercise bouts-high intensity interval exercise (HIIE) and exhaustive exercise session to voluntary fatigue-in a randomized cross-over trial. Pre-exercise PBMCs were incubated with 50% autologous serum (collected before and after each exercise bout) for 4 h. In vitro experiments revealed that post-HIIE serum reduced the histone H4 acetylation status and NF-κB content of PBMCs and suppressed the production of both TNF-α and IL-6 by PBMCs, while increasing IL-10 production. Post-exhaustive exercise serum induced histone H4 hyperacetylation and mitochondrial depolarization in lymphocytes and increased TNF-α production. In vitro post-HIIE serum incubation resulted in an increase in the frequencies of CD4 + CTLA-4 + and CD4 + CD25+ T cells expressing CD39 and CD73. Post-exhaustive exercise serum decreased the frequency of CD4 + CD25 + CD73+ T cells but increased CD4 + CD25-CD39 + T cell frequency. Both post-exercise serums increased the proportions of CD4 + PD-1 + and CD8 + PD-1+ T cells. Blood serum factors released during exercise altered the immune response and T cell phenotype. The type of exercise impacted the immunomodulatory activity of the post-exercise serum on PBMCs.

Mosquito colony maintenance in the laboratory is essential for research but presents logistical and ethical problems with the use of live animals for bloodfeeding. The Glytube is an artificial bloodfeeding system for mosquitoes that uses Parafilm-M® membrane and human blood to feed Aedes aegypti. This study evaluated the efficiency of Glytube with different types of membranes and chicken blood to feed Ae. aegypti and Ae. albopictus. We evaluated 2 artificial (thread seal tape [TST], Parafilm-M) and 2 natural membranes (pork, sheep intestine). The results for Ae. aegypti suggest that TST was the best membrane because it presented a high percentage of fed females (63%), a high average number of eggs per female (54.65), and an egg viability rate significantly similar to control (mouse). For Ae. albopictus, there was no significant difference between the membranes and the control; however, the use of TST is suggested due to the low cost and easy manipulation. The treatments that used chicken blood did not present significant differences in the egg viability when compared with the control. The Glytube functionality can be increased by replacing the Parafilm-M membrane by TST and human to chicken blood., (Copyright © 2020 by The American Mosquito Control Association, Inc.)

Obesity and physical inactivity threaten human health, and both could be solved with exercise. However, a higher amount of pollutants is inhaled during exercise. Exposure to air pollution increases the incidence and progression of diseases. Therefore, the aim of the study was to investigate the rate of pollution inhalation of lean, overweight, and obese individuals in a low and high-intensity hypothetical exercise session. Healthy sedentary men (n = 135) classified as lean, overweight, or obese were enrolled in our study. All participants performed a cardiopulmonary exercise testing (CPX) to collect ventilation rate (VE) data, which was used to predict total ventilation and pollutant inhalation of a 5-km running session. Air pollutant concentration of São Paulo City, Brazil was evaluated and the toxicological risk was estimated based on the potential intake dose. The concentrations of PM 2.5 were 29.57 μg/m 3 and 51.71 μg/m 3 , PM 10 were 45.85 μg/m 3 and 74 μg/m 3 , NO 2 were 63.71 μg/m 3 and 66.65 μg/m 3 , and O 3 were 69 μg/m 3 and 37 μg/m 3 , respectively in the summer and winter. In the hypothetical exercise session, total VE and time in both the first and second threshold were increased in the obese group (p < 0.001) (p < 0.001). The inhalation of PM 2.5 , PM 10 , NO 2 , and O 3 , during the hypothetical session, was increased in obese individuals (p < 0.001). Obese individuals should be considered a susceptible population, once they are more exposed to air pollution during exercise.

Stilobezzia Kieffer, 1911 is a diverse genus of predaceous Ceratopogonidae (Ceratopogoninae: Ceratopogonini) with 349 species recognized worldwide (Borkent Dominiak 2020). The genus has four subgenera, three occurs in Brazil, where Stilobezzia s. str. is the most speciose, with 23 species registered (Santarém Felippe-Bauer 2019).

The aim of this study was to evaluate the impact of high-intensity strength training (ST) or low-intensity strength training with blood flow restriction (ST-BFR) on monocyte subsets, the expression of C-C chemokine receptor 5 (CCR5), and CD16 on monocytes, and tumor necrosis factor alpha (TNF-α) production of overweight men. Thirty overweight men were randomly assigned to conventional ST or ST-BFR. Both groups performed exercises of knee extension and biceps curl with equal volume (3 sessions/week) over 8 weeks, and the peripheral frequency of monocytes (CD14+CD16-, classical monocytes; CD14+CD16+, intermediate monocytes; CD14-CD16+, nonclassical monocytes), the mean fluorescence intensity (MFI) of CCR5 and CD16 on CD14+ monocytes; and the production of TNF-α by lipopolysaccharide (LPS)-stimulated cells were quantified. Eight weeks of ST increased the frequency of CD14+CD16- monocytes ( p = 0.04) and reduced the percentage of CD14-CD16+ ( p = 0.02) and the production of TNF-α by LPS-stimulated cells ( p = 0.03). The MFI of CD16 on CD14+ monocytes decreased after the ST intervention ( p = 0.02). No difference in monocyte subsets, CCR5 or CD16 expression, and TNF-α production were identified after ST-BFR intervention ( p > 0.05). The adoption of ST promotes anti-inflammatory effects on monocyte subsets of overweight men, but this effect was lost when BFR was adopted. Novelty High-intensity strength training reduces the production of TNF-α and the peripheral frequency of CD16+ monocytes in overweight men. Blood flow restriction method blunts the strength training adaptations on monocyte subsets and pro-inflammatory TNF-α production in overweight men.

The toxicity of essential oils that can be used in insect pest management to pollinators needs further studies. Apis mellifera Linnaeus and Trigona hyalinata (Lepeletier) (Hymenoptera: Apidae) foragers were exposed by three pathways to ginger, mint, oregano and thyme essential oils to provide their LC 50, LD 50 and LC 90, LD 90 . Oregano and thyme were more toxic through contact and topically for A. mellifera while the toxicity of mint and ginger was lower. Trigona hyalinata was more tolerant to the essential oils than A. mellifera. In the walking test, the area was treated (totally or partially) with sub-doses (LC 50 ) obtained via contact. The area fully treated with oregano reduced the distance traveled and the movement speed increased the number of stops by A. mellifera. Similar results were observed for T. hyalinata with oregano and thyme oils. Apis mellifera showed irritability remaining shorter time in the area partially treated with ginger, mint and thyme essential oils while T. hyalinata had similar behavior with ginger and thyme. Essential oils did not repel A. mellifera or T. hyalinata, but those of ginger, mint and thyme reduced the time spent by A. mellifera in areas treated with sublethal doses. Oregano and thyme essential oils reduced the survival, mainly, of A. mellifera, while ginger and mint were selective for both pollinators.

Background: Obesity and low physical activity changes the redox state and neurotrophin secretion by leukocytes. However, the role of exercise on brain derived neurotrophic factor (BDNF) production and oxidative stress markers of peripheral blood mononuclear cells (PBMC) remains unknown. This study aimed to verify the impact of acute maximal exercise on oxidative stress markers and the BDNF production by stimulated PBMC from sedentary and physically active obese men., Methods: PBMC from twelve sedentary obese (SED group) and twelve regular exercisers (EXE group) obese men were collected before, immediately and 1-h after maximal exercise. PBMC were stimulated with lipopolysaccharide (LPS) to evaluate the BDNF and nitrite production, lipid peroxidation, and antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) activities., Results: PBMC from EXE group presented higher BDNF production (P=0.03) and lower TBARS levels than SED group at baseline. Maximal exercise increased BDNF and nitrite production, and lipid peroxidation immediately and 1-h after the bout in both groups. The EXE group presented higher superoxide dismutase activity immediately after bout and higher catalase activity 1-h after bout in PBMC. On the other hand, PBMC from SED group had lower superoxide dismutase activity immediately after exercise. Furthermore, PBMC from EXE group presented higher BDNF production and SOD activity and lower TBARS concentrations than SED group immediately after maximal exercise., Conclusions: Maximal exercise changes the redox state and enhances BDNF production by LPS-stimulated PBMC in obese individuals.

Introduction: Military personnel must remain physically active to meet operational requirements. Military physical training not only provides the performance capabilities required for performing occupational tasks but also fosters the development of sport. Thus, Armed Forces across the world have historically invested in developing elite- and Olympic-level athletes. This study aimed to assess the anthropometric and physiological differences among groups of Brazilian military athletes (MA), non-military athletes (A), and military non-athletes (M)., Materials and Methods: Seventy-five individuals participated in the study: 17 MA (23.7 ± 4.8 years), 27 A (24.7 ± 5.3 years), and 31 M (26.9 ± 3.3 years). MA and A individuals specialized in endurance sports, and had a mean weekly training volume of (100.0 ± 34.8 and 106.3 ± 40.5 Km; F = 0.894, p = 0.6), respectively. Anthropometric measures and maximal oxygen uptake (V̇O2máx) were assessed in all participants. Ergospirometry and anthropometry variables were analyzed with one-way analysis of variance (ANOVA) for independent measures. Comparisons of weekly training volume (km) and training experience (years) were performed only between the A and MA using the Student's t-test for independent samples. For a multidimensional approach, Partial least squares discriminant analysis (PLS-DA) was performed for all variables using the online tool MetaboAnalyst., Results: We found no differences in anthropometric and physiological profiles between A and MA, but significant differences between M and MA/A in body mass index (kg/m2) (BMI), body fat percentage, fat mass (kg), waist circumference (cm) (WC), somatotype, and V̇O2máx (mL min-1 kg-1)., Conclusion: In conclusion, military endurance athletes have similar anthropometric and physiological profiles to non-military athletes and superior levels to non-athlete military. These findings indicate that the Brazilian Armed Forces scouting system has been successful in identifying endurance athletic talent in line with their historic role of developing sport in Brazil., (© Association of Military Surgeons of the United States 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Thaumastocoris peregrinus spread to eucalyptus plantations in many countries. Chemical control is a questionable measure, mainly due to the environmental impact, high cost and moreover has the use restricted by the forest certifications. Bio-insecticides may have similar efficiency to chemical products to control T. peregrinus. The chemical thiamethoxam, thiamethoxam + lambda-cyhalothrin, acephate and the microbial Beauveria bassiana and Metarhizium anisopliae insecticides were tested at different doses to manage T. peregrinus. The products were sprayed on eucalyptus plants using aircraft and populations of this insect were counted before application and at 1, 14 and 21 days afterwards (DAA). Ten eucalyptus trees were evaluated per plot, with the collection of ten leaves from the middle third of the crown of each tree, and the number of T. peregrinus nymphs and adults obtained per leaf was determined. All the chemical insecticides had similar control at 1 DAA for T. peregrinus nymphs and adults. At 14 DAA, the number of T. peregrinus nymphs and adults on eucalyptus leaves was similar for the chemical and microbial insecticide treatments. At 21 DAA the control efficiency of T. peregrinus nymphs and adults was higher than 80% with all insecticides. The entomopathogenic insecticides have potential for aerial application to control T. peregrinus nymphs and adults and provide viable and environmentally-friendly alternative to manage this pest.

This work aimed to evaluate the inhibition of Candida rugosa lipase by five guanylhydrazone derivatives through biological, biophysical and theoretical studies simulating physiologic conditions. The compound LQM11 (IC 50  = 14.70 μM) presented the highest inhibition against the enzyme. Therefore, for a better understanding of the interaction process, spectroscopic and theoretical studies were performed. Fluorescence and UV-vis assays indicate a static quenching mechanism with non-fluorescent supramolecular complex formation and changing the native protein structure. The binding process was spontaneous (ΔG < 0) and electrostatic forces (ΔH < 0 and ΔS > 0) played a preferential role in stabilizing the complex ligand-lipase. The compounds were classified as non-competitive inhibitors using orlistat as a reference in competition studies. Based on the 1 H NMR assays it was possible to propose the sites of ligand (epitope) that bind preferentially to the enzyme and the theoretical studies were consistent with the experimental results. Finally, LQM11 was efficient as a lipase inhibitor of the crude intestinal extract of larvae of Rhynchophorus palmarum, an important agricultural plague, showing potential for control of this pest. Within this context, the real potential of this biotechnological application deserves further studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aim: To investigate the impact of physical fitness on the mobilization of CD4 + CD25 - CD39 + and CD4 + CD25 + CD39 + T cells in response to acute exercise., Methods: Fifteen high physical fitness (25.3 ± 1.4 years) and 15 low physical fitness (26.1 ± 1.9 years) men performed a single bout of high-intensity interval exercise (HIIE, 10 bouts of 60 seconds at 85% HRmax intercepted by 75 seconds of recovery at 50% HRmax). Blood lymphocytes were isolated before, immediately after and 1 hour after exercise for assessment of cell surface expression of CD25, CD39, and CD73 on CD4 + T cells. Effector memory T cells (mTeff) were identified by CD4 + CD25 - CD39 + coexpression, and memory regulatory T cells (mTReg) were defined as CD4 + CD25 + CD39 + T cells., Results: Exercise increased CD4 + and CD4 + CD25 + T cell frequencies immediately after followed by a decrease bellow to baseline values at 1 hour after the bout in both low and high physical fitness groups. At baseline, the proportions of mTeff were higher, while mTreg were lower in low physical fitness individuals. The frequency of mTreg increased immediately after HIIE in both groups, and remained higher 1 hour after the bout. However, high physical fitness individuals presented higher mTreg frequency in all periods evaluated. A significantly mobilization of mTeff cells was identified in both groups immediately after HIIE. High physical fitness individuals displayed a decrease in mTeff cells bellow to baseline, while the frequency of mTeff remained higher in low physical fitness group 1 hour after the bout. The peripheral frequency of CD4 + CD25 + CD73 + T cells increased in a similar way immediately after the bout in both groups, returning to the baseline values 1 hour after exercise. No differences in CD4 + CD25 - CD73 + T cells were observed after HIIE in both groups., Conclusion: Our results highlight the impact of physical activity status in the redistribution of CD4 + T cells expressing ectonucleotidases in response to HIIE., (© 2019 Wiley Periodicals, Inc.)

Acute Kidney Injury (AKI) is the main systemic complication and cause of death in viperid envenomation. Although there are hypotheses for the development of AKI, the mechanisms involved are still not established. The aim of this study was to evaluate the clinical-laboratorial-epidemiological factors associated with AKI in victims of Bothrops sp envenomation. This is an observational study carried out at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. AKI was defined according to the guidelines of the Acute Kidney Injury Network (AKIN). Among the 186 patients evaluated, AKI was observed in 24 (12.9%) after 48 hours of admission. Stage I was present in 17 (70.8%) patients, II in 3 (12.5%) and III in 4 (16.7%). Epidemiological characterization showed predominance of men, occurrence in rural areas, aged between 16-60 years, feet as the most affected anatomical region, and time to medical assistance less than 3 hours. Hypertension and diabetes were the comorbidities identified. Most of the accidents were classified as moderate, and clinical manifestations included severe pain, mild edema, local bleeding and headache. Laboratory results showed blood uncoagulability, hypofibrinogenemia, leukocytosis, increase of creatine kinase, and high lactate dehydrogenase levels. Multivariate analysis showed an association with high LDH levels [AOR = 1.01 (95% CI = 1.01-1.01, p<0.002)], local bleeding [AOR = 0.13 (95%CI = 0.027-0.59, p<0.009)], and the presence of comorbidities [AOR = 60.96 (95%CI = 9.69-383.30; p<0.000)]. Herein, laboratory markers such as high LDH levels along with local bleeding and comorbidities may aid in the diagnosis of AKI., Competing Interests: The authors have declared that no competing interests exist.

The interaction between bovine serum albumin (BSA) and thimerosal (TM), an organomercury compound widely employed as a preservative in vaccines, was investigated simulating physiological conditions and using different spectroscopic techniques. The results, employing molecular fluorescence showed the interaction occurs by static quenching through electrostatic forces (ΔH < 0 and ΔS > 0), spontaneously (ΔG = -4.40 kJ mol -1 ) and with a binding constant of 3.24 × 10 3  M -1 . Three-dimensional fluorescence studies indicated that TM causes structural changes in the polypeptide chain of the BSA, confirmed by circular dichroism that showed an increase in α-helix (from 43.9 to 47.8%) content after interaction process. Through synchronized fluorescence and employing bilirubin as a protein site marker, it was confirmed the preferential interaction of TM in the subdomain IB of BSA. The interaction mechanism proposed in this work is based on the reaction of TM with BSA through of free Cys34 residue, forming the adduct BSA-HgEt with the thiosalicylic acid release, which possibly interacts electrostatically with positive side chain amino acids of the modified protein. Finally, it was proven that both TM and EtHgCl accelerate the protein fibrillation kinetics in 42 and 122%, respectively, indicating the toxicity of these compounds in biological systems., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Micrurus snakes, commonly known as coral snakes, are responsible for 0.4% of the snakebites envenomings in Brazil. In this report, we describe a case of envenoming by Micrurus averyi, the black-headed coral snake, recorded in the western Brazilian Amazon. To the best of our knowledge, this is the first published case perpetrated by this species. The major complaint of the patient was an intense local pain and paresthesia. Examination of the bite site revealed edema extending from the left foot up the left leg that was accompanied by erythema involving the foot and distal third of the leg. Systemic signs at admission included nausea and drooling. The patient was treated with 100 mL of coral snake antivenom and intravenous analgesics (dipyrone) and was discharged 48 h post-admission with no complaints. The patient showed more intense local edema than that generally described in several other cases of Micrurus bites in Brazil., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Bothrops atrox is the snake responsible for the majority of snakebites in the Brazilian Amazon. Patients generally evolve to local manifestations such as edema, pain and ecchymoses. Systemic effects of B. atrox venom are usually restricted to blood incoagulability and spontaneous bleeding. However, in a few cases, bleeding in the central nervous system may occur, which can lead to sequels and deaths. Here, we report a case of a 59 year-old woman who presented edema, pain and ecchymoses on the right foot, headache, nausea, diarrhea, hypertension and blood incoagulability after the bite by Bothrops snake in the Brazilian Amazon. This case evolved with stroke resulting in death despite the antivenom and conservative therapy employed. In addition, we were able to identify the presence of venom in the patient's brain tissue after death. Direct action of toxins present in the snake's venom in the induction of systemic hemorrhage allied to blood incoagulability and hypertension presented by the patient could be involved in the mechanism of stroke in this case., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Secondary bacterial infections from snakebites contribute to the high complication rates that can lead to permanent function loss and disabilities. Although common in endemic areas, routine empirical prophylactic use of antibiotics aiming to prevent secondary infection lacks a clearly defined policy. The aim of this work was to estimate the efficacy of amoxicillin clavulanate for reducing the secondary infection incidence in patients bitten by Bothrops snakes, and, secondarily, identify risk factors for secondary infections from snakebites in the Western Brazilian Amazon., Methods and Findings: This was an open-label, two-arm individually randomized superiority trial to prevent secondary infection from Bothrops snakebites. The antibiotic chosen for this clinical trial was oral amoxicillin clavulanate per seven days compared to no intervention. A total of 345 patients were assessed for eligibility in the study period. From this total, 187 accomplished the inclusion criteria and were randomized, 93 in the interventional group and 94 in the untreated control group. All randomized participants completed the 7 days follow-up period. Enzyme immunoassay confirmed Bothrops envenoming diagnosis in all participants. Primary outcome was defined as secondary infection (abscess and/or cellulitis) until day 7 after admission. Secondary infection incidence until 7 days after admission was 35.5% in the intervention group and 44.1% in the control group [RR = 0.80 (95%CI = 0.56 to 1.15; p = 0.235)]. Survival analysis demonstrated that the time from patient admission to the onset of secondary infection was not different between amoxicillin clavulanate treated and control group (Log-rank = 2.23; p = 0.789).Secondary infections incidence in 7 days of follow-up was independently associated to fibrinogen >400 mg/dL [AOR = 4.78 (95%CI = 2.17 to 10.55; p<0.001)], alanine transaminase >44 IU/L [AOR = 2.52 (95%CI = 1.06 to 5.98; p = 0.037)], C-reactive protein >6.5 mg/L [AOR = 2.98 (95%CI = 1.40 to 6.35; p = 0.005)], moderate pain [AOR = 24.30 (95%CI = 4.69 to 125.84; p<0.001)] and moderate snakebites [AOR = 2.43 (95%CI = 1.07 to 5.50; p = 0.034)]., Conclusions/significance: Preemptive amoxicillin clavulanate was not effective for preventing secondary infections from Bothrops snakebites. Laboratorial markers, such as high fibrinogen, alanine transaminase and C-reactive protein levels, and severity clinical grading of snakebites, may help to accurately diagnose secondary infections., Trial Registration: Brazilian Clinical Trials Registry (ReBec): RBR-3h33wy; UTN Number: U1111-1169-1005.

Scorpion stings are a public health problem in the Brazilian Amazon. However, detailed clinical characterization with the proper animal identification is scarce. Here we report a confirmed case of envenoming by Tityus cf. silvestris in the Brazilian Amazon. The case evolved with generalized muscle spasms and was treated with antivenom and supportive therapy, requiring intensive care unit admission. The patient evolved favourably and was discharged after 9 days of hospitalization., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The Amazon region reports the highest incidence of snakebite envenomings in Brazil. We aimed to describe the epidemiology of snakebites in the state of Amazonas and to investigate factors associated with disease severity and lethality. We used a nested case-control study, in order to identify factors associated with snakebite severity and mortality using official Brazilian reporting systems, from 2007 to 2012. Patients evolving to severity or death were considered cases and those with non-severe bites were included in the control group. During the study period, 9,191 snakebites were recorded, resulting in an incidence rate of 52.8 cases per 100,000 person/years. Snakebites mostly occurred in males (79.0%) and in rural areas (70.2%). The most affected age group was between 16 and 45 years old (54.6%). Fifty five percent of the snakebites were related to work activities. Age ≤15 years [OR=1.26 (95% CI=1.03-1.52); (p=0.018)], age ≥65 years [OR=1.53 (95% CI=1.09-2.13); (p=0.012)], work related bites [OR=1.39 (95% CI=1.17-1.63); (p<0.001)] and time to medical assistance >6 hours [OR=1.73 (95% CI=1.45-2.07); (p<0.001)] were independently associated with the risk of severity. Age ≥65 years [OR=3.19 (95% CI=1.40-7.25); (p=0.006)] and time to medical assistance >6 hours [OR=2.01 (95% CI=1.15-3.50); (p=0.013)] were independently associated with the risk of death. Snakebites represent an occupational health problem for rural populations in the Brazilian Amazon with a wide distribution. These results highlight the need for public health strategies aiming to reduce occupational injuries. Most cases of severe disease occurred in the extremes of age, in those with delays in medical attention and those caused by Micrurus bites. These features of victims of snakebite demand adequate management according to well-defined protocols, including prompt referral to tertiary centres when necessary, as well as an effective response from surveillance systems and policy makers for these vulnerable groups.

The value of no-take marine reserves as fisheries-management tools is controversial, particularly in high-poverty areas where human populations depend heavily on fish as a source of protein. Spillover, the net export of adult fish, is one mechanism by which no-take marine reserves may have a positive influence on adjacent fisheries. Spillover can contribute to poverty alleviation, although its effect is modulated by the number of fishermen and fishing intensity. In this study, we quantify the effects of a community-managed marine reserve in a high poverty area of Northern Mozambique. For this purpose, underwater visual censuses of reef fish were undertaken at three different times: 3 years before (2003), at the time of establishment (2006) and 6 years after the marine reserve establishment (2012). The survey locations were chosen inside, outside and on the border of the marine reserve. Benthic cover composition was quantified at the same sites in 2006 and 2012. After the reserve establishment, fish sizes were also estimated. Regression tree models show that the distance from the border and the time after reserve establishment were the variables with the strongest effect on fish abundance. The extent and direction of the spillover depends on trophic group and fish size. Poisson Generalized Linear Models show that, prior to the reserve establishment, the survey sites did not differ but, after 6 years, the abundance of all fish inside the reserve has increased and caused spillover of herbivorous fish. Spillover was detected 1 km beyond the limit of the reserve for small herbivorous fishes. Six years after the establishment of a community-managed reserve, the fish assemblages have changed dramatically inside the reserve, and spillover is benefitting fish assemblages outside the reserve.

Leukemia is the most common blood cancer, and its development starts at diverse points, leading to distinct subtypes that respond differently to therapy. This heterogeneity is rarely taken into account in therapies, so it is still essential to look for new specific drugs for leukemia subtypes or even for therapy-resistant cases. Naphthoquinones (NQ) are considered privileged structures in medicinal chemistry due to their plethora of biological activities, including antimicrobial and anticancer effects. Nitrogen-containing heterocycles such as 1,2,3-1H-triazoles have been identified as general scaffolds for generating glycosidase inhibitors. In the present study, the NQ and 1,2,3-1H-triazole cores have been combined to chemically synthesize 18 new 1,2-furanonaphthoquinones tethered to 1,2,3-1H-triazoles (1,2-FNQT). Their cytotoxicities were evaluated against four different leukemia cell lines, including MOLT-4 and CEM (lymphoid cell lines) and K562 and KG1 (myeloid cell lines), as well as normal human peripheral blood mononucleated cells (PBMCs). The new 1,2-FNQT series showed high cytotoxic potential against all leukemia cell lines tested, and some compounds (12o and 12p) showed even better results than the classical therapeutic compounds such as doxorubicin or cisplatin. Others compounds, such as 12b, are promising because of their high selectivity against lymphoblastic leukemia and their low activity against normal hematopoietic cells. The cells of lymphoid origin (MOLT and CEM) were generally more sensitive than the myeloid cell lines to this series of compounds, and most of the compounds that showed the highest cytotoxicity were similarly active against both cell lines., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The enzyme dextransucrase in a medium containing sucrose and an acceptor as substrate synthesizes prebiotics oligosaccharides. The cashew apple juice works as a source of acceptors because it is rich in glucose and fructose (enzyme acceptors). The use of cashew apple juice becomes interesting because it aims at harnessing the peduncle of the cashew that is wasted during the nut processing, which is the product of greater economic expression. The production of dextransucrase enzyme was done by fermentative process by inoculating the bacterium Leuconostoc mesenteroides NRRL B512F into a culture medium containing sucrose as the only carbon source. Thus, the aim of this work was the production of prebiotic oligosaccharides by enzymatic process with addition of the dextransucrase enzyme to the clarified cashew apple juice. Dextran yield was favored by the combination of low concentrations of sucrose and reducing sugars. The formation of oligosaccharides was favored by increasing the concentration of reducing sugars and by the combination of high concentrations of sucrose and reducing sugars, the highest concentration of oligosaccharides obtained was 104.73 g/L and the qualitative analysis showed that at concentrations of 25 g/L and 75 g/L of sucrose and reducing sugar, respectively, it is possible to obtain oligosaccharides of degree of polymerization up to 12. The juice containing prebiotic oligosaccharide is a potential new functional beverage.

Sea bream scales were subjected to enzymatic hydrolysis with Esperase, and a peptide fraction with a molecular mass <3kDa (F3) was isolated by ultrafiltration. F3 was encapsulated in nanoliposomes made of partially purified phosphatidylcholine (PC). Concentrations of 3.1% and 1mg/ml for PC and F3, respectively, were established as the best entrapment protocol by response surface methodology. The liposomes entrapment efficiency and zeta potential were 74.6±0.9% and -40.8±0.67mV, respectively. The liposome size ranged from 66.2 to 214nm, with a mean diameter of 90.3nm and a polydispersity index of 0.25. The antioxidant activity and ACE inhibitory activity of the encapsulated peptide fraction (L-F3) remained constant after 8days at 4°C. Encapsulation preserved the biological activities of F3, and could therefore be an alternative to improve the stability of these compounds when applied to a food product., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Antibiotic resistance is considered one of the world's major public health concerns. The main cause of bacterial resistance is the improper and repeated use of antibiotics. To alleviate this problem, new chemical substances against microorganisms are being synthesized and tested. Thiazolidines are compounds having many pharmacological activities including antimicrobial activities. For this purpose some thiazolidine derivatives substituted at position 5 in the thiazolidine nucleus were synthesized and tested against several microorganisms. Using a disc diffusion method, antimicrobial activity was verified against Gram-positive, Gram-negative, and alcohol acid resistant bacteria and yeast. The minimum inhibition concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined. All derivatives showed antimicrobial activity mainly against Gram-positive bacteria, with MIC values ranging from 2 to 16 µg/mL.

Objective. This study aimed to compare the prevalence and morbidity data on Schistosoma mansoni infection in two rural areas: the Jequitinhonha valley (area 1) and the Rio Doce valley (area 2) in the state of Minas Gerais, Brazil, covering the period from 2007 to 2010. Material and Methods. The parasitological stool tests were based on the quantitative method of Kato modified by Katz et al. Three clinical forms were considered: type I-schistosomiasis infection, type II-hepatointestinal form, and type III-hepatosplenic form. Results. The prevalence of infection among inhabitants of area 1 was 22.9%, with 2.1% presenting the hepatosplenic form and two cases of schistosomal myeloradiculopathy. The infection prevalence rate in area 2 was 20.2%, with 3.3% presenting the hepatosplenic form. Conclusion and Recommendation. There was no difference in the prevalence and in the morbidity of Schistosoma mansoni infection between the two areas, but it was predominant in young men with a low intensity of infection. The cases of schistosomal myeloradiculopathy in area 1 can be highlighted: these emphasize that schistosomiasis should not be neglected in Brazil. The lack of infection control in both areas may be related to the poor sanitation system, the absence of previous treatment, and the reinfection process.