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Sporotrichosis is a fungal anthropozoonosis that has become a major public health problem in tropical countries. With that in mind, this study analyzed the relationship between this disease and demographic, socioeconomic and public health issues in Belém, State of Pará, Brazil, from 2020 to 2022. This ecological and cross-sectional study used data from the Belém Zoonosis Control Center, the Brazilian Institute of Geography and Statistics and the Health Ministry. Descriptive and spatial analyses were performed employing significance statistical, kernel, buffer and Moran techniques. One hundred sporotrichosis cases in cats and 49 in humans were analyzed. The results showed that the individuals most affected were women (61.22 %), adults (87.76 %), with the cutaneous form (95.92 %), diagnosed histopathologically (38.78 %), still undergoing treatment (46.94 %) and that the form of contagion was through cat scratches or bites (73.47 %). The profile also showed quantitative significance of ignored data related to treatment (65.31 %) and cat presence at home (63.27 %). The disease had a non-homogeneous distribution with very high densities in Campina de Icoaraci, Águas Negras and Parque Guajará. Those neighborhoods presented a very low Living Conditions Index and precarious services and health centers. The spatial dependence between the environmental and socioeconomic studied variables evidenced the establishment of an active transmission circuit for sporotrichosis in peripheral areas of the city, related to health inequalities with an underlying possible epidemiological silence, suggesting the need for expanding One Health public policies, aiming the sustainable development., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

2,3-Butanediol (2,3-BD) is a highly valued building block, and optimizing its production by fermentation, particularly with crude glycerol, is crucial. Enterobacter aerogenes is a key microorganism for this process; however, there are limited studies addressing the inhibition effects of products and by-products on 2,3-BD production. This study investigates these inhibition effects to maximize 2,3-BD production. Final concentrations of 2,3-BD plus acetoin reached 89.3, 92.7, and 71.1 g.L -1 with productivities of 1.22, 1.69, and 0.99 g.L -1 .h -1 in pure glycerol, glucose, and crude glycerol media, respectively. Acetic acid was the main by-product, with concentrations ranging from 10 to 15 g.L -1 . The reinoculation of E. aerogenes cells highlighted the strong effect of 2,3-BD and acetic acid on microbial growth and metabolism, with the cultivation environment exerting selective pressure. Notably, cells reuse enhanced performance in crude glycerol media, achieving a specific productivity in relation to biomass (Y P/X ) of 9.18 g.g -1 ; about 25% higher than in fed-batch without cells reuse. By combining results from two fed-batch cycles, the total final concentration of 2,3-BD plus acetoin reached 99.4 g.L -1 , alongside a 33% reduction in total acetic acid production with reused cells.

Introduction: The purpose of this study was to evaluate whether the mixing method of AH Plus Jet sealer affects its physicochemical and mechanical properties., Methods: The properties of AH Plus Jet sealer were analyzed when mixed using either the Auto Mix Tip or manual mixing. The evaluated properties included radiopacity (n = 5), initial and final setting times (n = 5), flow (n = 5), and solubility (n = 3), following specifications outlined in ISO 6876/2012 and ADA Nº 57/2000. pH levels were measured at intervals of 3, 24, 72, and 168 hours (n = 10). The push-out bond strength test was conducted using a universal testing machine and using bovine teeth (n = 30). Failure modes were analyzed with stereomicroscopy. Porosity was evaluated under micro-CT (n = 5), and scanning electron microscopy was also performed (n = 5). One-way analysis of variance and Tukey, unpaired t-tests, or Mann-Whitney tests were used with a significance level of 5%., Results: The Auto Mix exhibited a radiopacity value of 12.11 mmAl, whereas manual mixing resulted in 12.55 mmAl (P > .05). For initial and final setting times, Auto Mix showed 901 minutes and 1779 minutes, respectively, while manual mixing recorded values of 631 minutes and 1504 minutes (P < .05). In terms of flow, Auto Mix demonstrated higher values (25.26 mm) than manual mixing (21.71 mm) (P < .05). No statistical differences were observed between the two methods for solubility and pH (P > .05). Manual mixing presented a higher bond strength value (14.52 MPa) than Auto Mix (9.81 MPa) (P < .05). The mixed failure mode was the most frequent outcome for both methods. The highest porosity was observed for Auto Mix (P < .05). Scanning electron microscopy analysis revealed that manual mixing resulted in a smoother surface with fewer pores and smaller, more evenly distributed agglomerates compared to automatic mixing., Conclusion: The mixing method employed for AH Plus Jet sealer influences some physicochemical and mechanical properties of the material., (Copyright © 2024 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Conversion of heterotrophic organisms into partially or completely autotrophic organisms is primarily accomplished by extensive metabolic engineering and laboratory evolution efforts that channel CO 2 into central carbon metabolism. Here, we develop a directed endosymbiosis approach to introduce carbon assimilation in budding yeasts. Particularly, we engineer carbon assimilating and sugar-secreting photosynthetic cyanobacterial endosymbionts within the yeast cells, which results in the generation of yeast/cyanobacteria chimeras that propagate under photosynthetic conditions in the presence of CO 2 and in the absence of feedstock carbon sources like glucose or glycerol. We demonstrate that the yeast/cyanobacteria chimera can be engineered to biosynthesize natural products under the photosynthetic conditions. Additionally, we expand our directed endosymbiosis approach to standard laboratory strains of yeasts, which transforms them into photosynthetic yeast/cyanobacteria chimeras. We anticipate that our studies will have significant implications for sustainable biotechnology, synthetic biology, and experimentally studying the evolutionary adaptation of an additional organelle in yeast., (© 2024. The Author(s).)

Background: Leishmania (Viannia) braziliensis Thor strain exhibits a heterogeneous composition comprised of subpopulations with varying levels of infectivity. Clonal subpopulations were previously obtained from the strain Thor by sorting single-parasites and proceeding cultivation. The subpopulations used in this study are named Thor03, Thor 10 and Thor22., Objectives: Phenotypic characteristics of the parasite, specially focusing on virulence factors and resistance to the antimicrobial mechanisms of macrophages, were investigate in these subpopulations., Methods: Cellular and molecular biology, as well as biochemistry approaches were applied to obtain the data analysed in this study., Findings: Relative quantification of gene expression was measured for calpain, cysteine protease B (CPB), and subtilisin proteases but no significant differences in these genes' expression among subpopulations was observed. However, subtilisin and CPB proteins were assessed as more abundant in Thor03 by fluorescence-labelled flow cytometry technique. Western Blotting assays, as semi-quantitative analysis in gel, showed higher concentrations of subtilisin (110 to 50 kDa) and CPB (40 to 18 kDa) in extract of intracellular amastigotes from subpopulations Thor03 and Thor10 and calpain (60 to 25 kDa) showed no significant differences among subpopulations. Complementary, higher trypanothione reductase activity was observed in Thor10 intracellular amastigotes and assays of susceptibility to hydrogen peroxide-inducing agents and nitric oxide donors conducted with promastigotes revealed greater resistance to in vitro oxidative stress induction for Thor10, followed by Thor03., Main Conclusions: The data obtained for the virulence factors explored here suggest how multiple coexisting phenotypic-distinct subpopulations may contribute in adaptability of a single L. (V.) braziliensis strain during infection in the host cells.

The use of antimicrobials in swine production is an issue that concerns the whole world due to their impact on animal and public health. This study aimed to verify the antimicrobial use in 29 commercial full-cycle farms in the midwestern region of the state of Minas Gerais, since this region is a hub of intensive pig farming in Brazil, as well as the possible correlations between the use of antimicrobials, biosecurity, and productivity. A total of 28 different drugs used for preventive purposes were described. On average, the herds used seven drugs, exposing the piglets for 116 days and totaling 434.17 mg of antimicrobials per kilogram of pig produced. Just eight active ingredients made up 77.5% of the total number of drugs used on the studied herds. Significant differences were found between the variables, biosecurity score and number of sows, antimicrobial amount and number of drugs, number of drugs and number of sows, and between productivity and biosecurity scores. The use of antimicrobials was considered excessive in the swine farms in the state of Minas Gerais compared to what was reported in Brazil and in other countries. Educational measures and better control should be proposed to reduce the preventive use of antimicrobials.

Two C -methylated fluostatins (FSTs) B3 (1) and B4 (2) were synthesized from flavin-mediated nonenzymatic epoxide ring-opening reactions of FST C. The structures of 1 and 2 were elucidated by HRESIMS, NMR, and ECD spectroscopic analyses. A subsequent 13 C labeling study demonstrated that the C -methyl groups of 1 and 2 were derived from DMSO and enabled the mechanistic proposal of a nonenzymatic C -methylation.

Introduction: The obturation quality of the mandibular molar mesial canals and isthmuses with two thermoplastic techniques, ultrasonic vertical condensation (UVC) and continuous wave of condensation (CWC), was evaluated using computed microtomography (μCT)., Methods: Thirty-six human mandibular molars had been previously scanned and analyzed using μCT for mesial roots with morphologically similar isthmuses for this study. Coronal access and confirmation of foraminal patency were performed, and the actual length of the teeth was established using a clinical microscope (40X magnification). The canals were prepared using ProTaper Gold instruments up to #F3, with 2.5% sodium hypochlorite as the irrigant solution, followed by a passive ultrasonic irrigation protocol. The specimens were randomly divided into the UVC and CWC groups based on the obturation technique to be used. Obturation was performed with #F3 gutta-percha cones cemented using AH Plus Jet sealer. The μCT scans were performed after 15 days, and the images were evaluated by a calibrated examiner blinded to the experimental groups to determine the filling rate of the entire canal area, including the main canal and isthmus. Student's t-test was used for statistical analysis; P values ≤0.05 were considered significant., Results: Neither of the thermoplastic obturation techniques achieved complete filling of the canals (86.3% for UVC and 91.4% for CWC), with a statistically significant difference between them (P = .029)., Conclusions: Under the conditions of the study, it can be concluded that none of the techniques completely filled the canal/isthmus of the mandibular molars; however, the CWC exhibited better performance., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: Malaria is a parasitosis conditioned by several factors. This study sought to analyze the spatial distribution of malaria considering environmental, socioeconomic, and political variables in São Félix do Xingu, Pará, Brazil, from 2014 to 2020., Methods: Epidemiological, cartographic, and environmental data were obtained from the Ministry of Health, Brazilian Geographical and Statistical Institute, and National Space Research Institute. Statistical and spatial distribution analyses were performed using chi-squared tests of expected equal proportions and the kernel and bivariate global Moran's techniques with Bioestat 5.0 and ArcGIS 10.5.1., Results: The highest percentage of cases occurred in adult males with brown skin color, mainly placer miners, with a primary education level, living in rural areas, who were infected with Plasmodium vivax and with parasitemia of two or three crosses as diagnosed by the thick drop/smear test. The disease had a non-homogeneous distribution, with distinct annual parasite indices associated with administrative districts and clusters of cases in locations with deforestation, mining, and pastures close to Conservation Units and Indigenous Lands. Thus, a direct relationship between areas with cases and environmental degradation associated with land use was demonstrated, along with the precarious availability of health services. Pressure on protected areas and epidemiological silence in Indigenous Lands were also noted., Conclusions: Environmental and socioeconomic circuits were identified for development of diseases associated with precarious health services in the municipality. These findings highlight the need to intensify malaria surveillance and contribute to the systematic knowledge of malaria's epidemiology by considering the complexity of its conditioning factors.

Precision and organization govern the cell cycle, ensuring normal proliferation. However, some cells may undergo abnormal cell divisions (neosis) or variations of mitotic cycles (endopolyploidy). Consequently, the formation of polyploid giant cancer cells (PGCCs), critical for tumor survival, resistance, and immortalization, can occur. Newly formed cells end up accessing numerous multicellular and unicellular programs that enable metastasis, drug resistance, tumor recurrence, and self-renewal or diverse clone formation. An integrative literature review was carried out, searching articles in several sites, including: PUBMED, NCBI-PMC, and Google Academic, published in English, indexed in referenced databases and without a publication time filter, but prioritizing articles from the last 3 years, to answer the following questions: (i) "What is the current knowledge about polyploidy in tumors?"; (ii) "What are the applications of computational studies for the understanding of cancer polyploidy?"; and (iii) "How do PGCCs contribute to tumorigenesis?"

Objective: This study aimed to assess diagnostic radiology training and exposure during medical school, from the perspective of medical students in Brazil., Methods: In this multicenter study approved by the Institutional Review Board, medical students from multiple universities in Brazil filled out an online questionnaire regarding their perception about diagnostic radiology training during medical school, including knowledge and use of the American College of Radiology Appropriateness Criteria and their confidence level in interpreting common radiological findings. Medical students from different regions of Brazil were sent invitations to participate in the anonymous survey through radiology group emails initiated by radiology professors and a group of ambassadors representing different institutions. Informed consent was obtained electronically at the beginning of the survey., Results: The survey demonstrated diagnostic radiology is frequently included in preclinical exams; however, radiology training during medical school was considered inadequate from the medical students´ perspective. Overall, radiological imaging teaching was provided by radiologists for more than half of the survey respondents; however, radiological imaging is frequently shown to students by non-radiologist physicians during case discussion rounds. Moreover, few respondents had a mandatory radiology training rotation during medical school., Conclusion: This Brazilian medical student survey demonstrated that from the medical students' perspective, diagnostic radiology is an important subject in clinical practice; however, their radiology training and exposure are overall heterogeneous.

Unexplained infertility has a huge social impact and is a significant challenge for both clinicians and researchers. Previous studies have shown the involvement of multiple factors in infertility. Among these, the subset of regulatory T cells is of particular interest for the maternal tolerance towards the semi-allogenic fetus. We investigated circulating CD45RA + regulatory and non-regulatory CD4 + T cells in healthy women and patients with unexplained infertility in the context of thymic output and peripheral proliferation. The proportion of FOXP3 + and FOXP3 - CD45RA + CD4 + T cells in peripheral blood was studied in control groups of healthy parous and nulliparous (never-pregnant) women and in patients with unexplained infertility. In the same groups thymic output and peripheral proliferation were defined by the sj/βTREC ratio, and signal joint T-cell receptor excision circles (sjTREC) and Ki67 expression, respectively. In parous women a decrease in sjTREC/10 5 cells and CD45RA + T lymphocytes, compared to nulliparous group was found. At the same time, the proportion of FOXP3 - CD45RA + CD4 + cells, but not FOXP3 + CD45RA + Tregs was reduced. In contrast, in patients with unsuccessful pregnancy, proportions of both regulatory and non-regulatory T cell counterparts were lower. Taken together, our results provide evidence for group-specific properties in the CD45RA + T cell compartment between healthy parous, nulliparous and women with unexplained infertility., Competing Interests: Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Due to the significant shortage of therapeutic options for carbapenem-resistant Enterobacterales (CRE) infections, new drugs or therapeutic combinations are urgently required. We show in this study that (-)-camphene-based thiosemicarbazide (TSC) may act synergistically with polymyxin B (PMB) against CRE, rescuing the activity of this antimicrobial. With the specific aim of a better molecular understanding of this effect caused by the presence of TSC, theoretical calculations were also performed in this study. Based on these findings, it is concluded that the presence of TSC moieties contributes to significant changes in the hydrogen atom charge of PMB structure, which trend more positives for the PMB/TSC system studied. This could lead to the formation of stronger hydrogen bonds in the Enterobacterales active site and, thus contribute to a molecular understanding of the PMB rescue of activity promoted by the presence of TSC moiety. As such, the clinical potential of these drug combinations requires further evaluation.

Xanthone-containing natural products display diverse pharmacological properties. The biosynthetic mechanisms of the xanthone formation have not been well documented. Here we show that the flavoprotein monooxygenase FlsO1 in the biosynthesis of fluostatins not only functionally compensates for the monooxygenase FlsO2 in converting prejadomycin to dehydrorabelomycin, but also unexpectedly converts prejadomycin to xanthone-containing products by catalyzing three successive oxidations including hydroxylation, epoxidation and Baeyer-Villiger oxidation. We also provide biochemical evidence to support the physiological role of FlsO1 as the benzo[b]-fluorene C5-hydrolase by using nenestatin C as a substrate mimic. Finally, we resolve the crystal structure of FlsO1 in complex with the cofactor flavin adenine dinucleotide close to the "in" conformation to enable the construction of reactive substrate-docking models to understand the basis of a single enzyme-catalyzed multiple oxidations. This study highlights a mechanistic perspective for the enzymatic xanthone formation in actinomycetes and sets an example for the versatile functions of flavoproteins., (© 2022. The Author(s).)

Functional annotation of Trametes villosa genome was performed to search Class II peroxidase proteins in this white-rot fungus, which can be valuable for several biotechnological processes. After sequence identification and manual curation, five proteins were selected to build 3 D models by comparative modeling. Analysis of sequential and structural sequences from selected targets revealed the presence of two putative Lignin Peroxidase and three putative Manganese Peroxidase on this fungal genome. All 3 D models had a similar folding pattern from selected 3 D structure templates. After minimization and validation steps, the best 3 D models were subjected to docking studies and molecular dynamics to identify structural requirements and the interactions required for molecular recognition. Two reliable 3 D models of Class II peroxidases, with typical catalytic site and architecture, and its protein sequences are indicated to recombinant production in biotechnological applications, such as bioenergy.Communicated by Ramaswamy H. Sarma.

Epoxide ring opening reactions are common and important in both biological processes and synthetic applications and can be catalyzed in a non-redox manner by epoxide hydrolases or reductively by oxidoreductases. Here we report that fluostatins (FSTs), a family of atypical angucyclines with a benzofluorene core, can undergo nonenzyme-catalyzed epoxide ring opening reactions in the presence of flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NADH). The 2,3-epoxide ring in FST C is shown to open reductively via a putative enol intermediate, or oxidatively via a peroxylated intermediate with molecular oxygen as the oxidant. These reactions lead to multiple products with different redox states that possess a single hydroxyl group at C-2, a 2,3-vicinal diol, a contracted five-membered A-ring, or an expanded seven-membered A-ring. Similar reactions also take place in both natural products and other organic compounds harboring an epoxide adjacent to a carbonyl group that is conjugated to an aromatic moiety. Our findings extend the repertoire of known flavin chemistry that may provide new and useful tools for organic synthesis., (© 2022. The Author(s).)

Dyslipidemia is described as a hallmark of metabolic syndrome, promoting a stage of metabolic inflammation (metainflammation) that could lead to misbalances in energetic metabolism, contributing to insulin resistance, and modifying intracellular cholesterol pathways and the renin-angiotensin system (RAS) in pancreatic islets. Low-density lipoprotein (LDL) hypercholesterolemia could disrupt the tissue communication between Langerhans β-cells and hepatocytes, wherein extracellular vesicles (EVs) are secreted by β-cells, and exposition to LDL can impair these phenomena. β-cells activate compensatory mechanisms to maintain insulin and metabolic homeostasis; therefore, the work aimed to characterize the impact of LDL on β-cell cholesterol metabolism and the implication on insulin secretion, connected with the regulation of cellular communication mediated by EVs on hepatocytes. Our results suggest that β-cells can endocytose LDL, promoting an increase in de novo cholesterol synthesis targets. Notably, LDL treatment increased mRNA levels and insulin secretion; this hyperinsulinism condition was associated with the transcription factor PDX-1. However, a compensatory response that maintains basal levels of intracellular calcium was described, mediated by the overexpression of calcium targets PMCA1/4, SERCA2, and NCX1, together with the upregulation of the unfolded protein response (UPR) through the activation of IRE1 and PERK arms to maintain protein homeostasis. The LDL treatment induced metainflammation by IL-6, NF-κB, and COX-2 overexpression. Furthermore, LDL endocytosis triggered an imbalance of the RAS components. LDL treatment increased the intracellular levels of cholesterol on lipid droplets; the adaptive β-cell response was portrayed by the overexpression of cholesterol transporters ABCA1 and ABCG1. Therefore, lipotoxicity and hyperinsulinism induced by LDL were regulated by the natural compound auraptene, a geranyloxyn coumarin modulator of cholesterol-esterification by ACAT1 enzyme inhibition. EVs isolated from β-cells impaired insulin signaling via mTOR/p70S6Kα in hepatocytes, a phenomenon regulated by auraptene. Our results show that LDL overload plays a novel role in hyperinsulinism, mechanisms associated with a dysregulation of intracellular cholesterol, lipotoxicity, and the adaptive UPR, which may be regulated by coumarin-auraptene; these conditions explain the affectations that occur during the initial stages of insulin resistance.

The use of teleophthalmology may be a viable strategy to track and to diagnose major eye diseases primary health care patients. This study aimed to describe the performance of 30,315 telediagnoses in ophthalmology in primary care patients and the case management of this service. This is a cross-sectional study to evaluate the telediagnosis performed in patients treated at the eight remote points of the TeleOftalmo project from January 2nd, 2018, to December 31st, 2020. The patients' demographic characteristics, the reasons for referral, the diagnoses made according to age group, and the case management of the telediagnosis were evaluated. Most patients were female (66.1%), adults (70.3%), and referred to telediagnosis mainly due to reduced visual acuity (60.5%). Refractive errors were the most prevalent diagnosis in all age groups. Presbyopia was the most prevalent eye disease in adults (65.4%) and older adults (64%), followed by cataracts (41.3%) and suspected glaucoma (10.6%) in older adults. In total, 30,315 patients underwent telediagnosis, 70.5% had their ocular complaints fully resolved, without the need for referral to an in-person ophthalmologist. Telemedicine can be resolutory for the most prevalent eye diseases in the population, increasing the supply of diagnoses, qualifying and assisting in reducing waiting lines for ophthalmologic care.

This study aimed to evaluate the root canal real length (RL) changes due to the mechanical instrumentation use with different flaring magnitudes. After access cavity, 60 mesial root canals of mandibular molars were randomly separated in three groups: Hyflex EDM (HF; #25/.12, #10/.05 e #25/~), Reciproc Blue (RB; R25), and MTwo (M2; #10/.04, #15/.05, #20/.06 e #25/.06). The RL was defined as the apical limit, and 2.5% sodium hypochlorite irrigating solution was chosen. After the access cavity (RL 1), cervical flaring (RL 2), and complete chemical-mechanical preparation (RL 3), the RL was evaluated. The RL was evaluated by a blind examiner with the aid of a microscope (16x) placing the endodontic file stop at the coronary reference. When comparing length measurements, the RL was shorter before instrumentation than that after instrumentation. A reduction of 0.65 mm (HF), 0.61 mm (RB), and 0.48 mm (M2) was observed. However, among groups, no statistical differences were found (p > 0.05). Under the conditions tested, it can be inferred that all mechanical systems provoked RL variations, which emphasizes the need for constant verification of the odontometry, mainly before root canal obturation.

Brucellosis is one of the most important and widespread bacterial zoonotic diseases worldwide, and it is transmitted to humans from various sources, including direct contact with infected animals and the ingestion of contaminated products, including unpasteurized milk. There are only a few epidemiological studies on said disease in humans in Western Santa Catarina, a region instantiated by agriculture. Thus, the objective of this study was to characterize the epidemiological aspects of human brucellosis reported in Western Santa Catarina from 2013 to 2018. The data were provided by the Epidemiological Surveillance Board (Diretoria de Vigilancia Epidemiologica). The frequency of the disease in humans and the epidemiological profile of confirmed human cases were evaluated. Cases that were screened positive and those that were confirmed and submitted to the therapeutic protocol were analyzed. During the study period, 3,671 people were tested, of which 12.34% were screened positive (453/ 3,671) and 3.40% were confirmed (125/3,671). The year with the highest number of people testing positive was 2015 (123 cases), and 2018 was the year with the highest number of confirmed cases (39 cases). Confirmed cases predominated in males (48.8%), self-declared white (22.4%), aged 20-59 years old (60%), with incomplete primary education (22.4%), of rural origin (59.2%), with occupational contact with cattle (64.8%), engaged in professions directly linked to agricultural and livestock activities (55.5%), and who reported consumption of unpasteurized dairy products (59.2%). No seasonal variation was observed in case numbers. The results demonstrated that brucellosis is an endemic disease in Western Santa Catarina.

Introduction:  Endometriosis is an inflammatory disease that affects women of reproductive age, causing pain and the possibility of infertility. Endometriosis was associated to low life quality and research shows the impact of endometriosis in several areas of life, justifying how these patients are more likely to develop depression, anxiety, and stress., Objective:  The aim of the present systematic review was to explore the field of psychology in endometriosis, identifying studies that used the cognitive behavioral therapy technique as a treatment for endometriosis and chronic pelvic pain., Methods:  The keywords used were Endometriosis and Behavioral Therapy; Behavioral Disciplines and Activities ; Cognitive Behavioral Therapy ; Mental Health ; Psychological Techniques ; Psychology ; Psychotherapy ; Mental Health Services ; and the search was performed in the following databases: PubMed/Medline, Scielo, Lilacs, and Capes. The study followed the PRISMA guidelines and all studies whose intervention strategy used was related to cognitive-behavioral therapy were considered., Results:  Of the 129 articles found, only 5 were selected, and it was possible to identify that the psychological intervention whose approach brought cognitive-behavioral therapy techniques promoted a decrease in the sensation of pain, improvements in the scores of depression and stress, and significant changes in aspects of quality of life such as vitality, physical and social functioning, emotional well-being, control, and autonomy., Conclusion:  Cognitive-behavioral therapy can be very promising to take care of the emotional side of those who have endometriosis However, the present systematic review highlights the need to develop more structured studies with consistent, clear and replicable methods to reach a psychological intervention protocol for patients who live with this gynecological-physical-emotional condition., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Antimicrobial resistance is a global problem that puts the population's health at risk. This paper aims to identify and evaluate strategies for the prevention and control of antimicrobial resistance, and barriers to their implementation in Primary Health Care (PHC) services. We developed an evidence brief for policies. The search for evidence occurred in 13 databases from November to December 2018. A deliberative dialogue was performed to validate the results and we identified barriers and facilitators to implementing the strategies. The 13 systematic reviews included evidenced that the interventions focused on education, use of electronic systems and biomarkers reduced antimicrobial consumption and prescription. User/caregiver's expectation to receive antibiotic prescriptions was the main obstacle to implementing strategies, while education actions involving health professionals were facilitators. The rational use of medications in the PHC services is crucial to prevent antimicrobial resistance to antibiotics. The interventions identified in this study can be implemented alone or combined, according to local context.

Marine-derived fungi are a promising source of bioactive molecules, especially species from extreme habitats. Although several secondary metabolites such as meroterpenoids and alkaloids have been isolated from cultures of Aspergillus fischeri, obtained from terrestrial habitats, there is no report on compounds isolated from marine-derived strains. Many metabolites isolated from marine-derived fungi exhibited a myriad of biological activities. Marine natural products have shown to be an important source of bioactive compounds and can assist in the discovery of molecules with affinity against validated targets from exclusive strains of parasites of medical importance such as pteridine reductase 1 (PTR1), from Leishmania major, which is essential for cell growth. Leishmaniasis is responsible for approximately 65,000 annual deaths. Despite the mortality data, drugs available for the treatment of patients are insufficient and have moderate therapeutic efficacy in addition to serious adverse effects, which make the development of new drugs urgent. The previously described aszonalenin (ASL), aszonapyrone A (ASP), acetylaszonalenin (ACZ), and helvolic acid (HAC) were isolated from the ethyl acetate extract of the culture of a marine sponge-associated A. fischeri MMERU 23 and their affinities against PTR1 were determined by ThermoFluor®. Among the tested compounds, only ACZ showed dose-dependent affinity against PTR1. Moreover, complementary molecular dynamics studies ( t  = 100 000 ps) have showed that this molecule performs hydrogen bonds with key residues at the active site for more than 60% of the productive trajectory time. The results indicate that ACZ could be a promising PTR1 inhibitor and a potential candidate for development of antileishmanial drug.Communicated by Ramaswamy H. Sarma.

The visceral form of Leishmaniasis, also known as kala-azar, caused by Leishmania chagasi is the main etiological agent of this form in Brazil responsible for 30,000 annual deaths. Despite its epidemiological impact, treatment of the disease is limited by resistance, species-dependent efficacy and serious adverse effects. The application of computational tools to prioritize potential bioactive molecules based on 3D structural of biological target is a viable alternative. Among the L. chagasi validated targets, Fe + 2 superoxide dismutase B2 (LcFeSODB2) is the first parasite enzyme against oxidative stress and it is involved in essential metabolic processes for its survival. Due to substrate binding-site volume (superoxide ion) and consequent difficulty in its active site modulation for small molecules, the search for allosteric sites at LcFeSODB2 3D structure is a promising strategy. As there are no 3D structures of LcFeSODB2, comparative modeling was applied to build 3D models by SWISS-MODEL and MODELLER version 9.19. Next, the best 3D model was used in molecular dynamics (MD) routines with multiple probes on GROMACS version 5.1.2. In addition, potential allosteric sites predicted by FTMap and Metapocket web servers were used with probe occupancy maps from MD to select an allosteric binding site and propose a pharmacophore model. Next, it was used as a template in virtual screening by UNITY ® module available on SYBYL-X version 2.1.1 at Sigma-Aldrich CPR™ subset of ZINC12 database. The pharmacophore-based virtual screening resulted in the selection of two potential allosteric LcFeSOD compounds with partial pharmacophoric requirements, drug-like properties and commercial availability for enzymatic assays. Communicated by Ramaswamy H. Sarma.

Berninamycins are a class of thiopeptide antibiotics with potent activity against Gram-positive bacteria. Heterologous expression of the berninamycin ( ber ) biosynthetic gene cluster from marine-derived Streptomyces sp. SCSIO 11878 in different terrestrial model Streptomyces hosts led to the production of berninamycins A (1) and B (2) in Streptomyces lividans SBT18 and Streptomyces coelicolor M1154, while two new linearized berninamycins J (3) and K (4) were obtained in Streptomyces albus J1074. Their structures were elucidated by detailed interpretation of NMR data and Marfey's method. Bioactivity assays showed that the linear thiopeptides 3 and 4 were less potent than 1 and 2 in antibacterial activity. This work indicates that undefined host-dependent enzymes might be responsible for generating the linear thiopeptides 3 and 4 in S. albus J1074.

Purpose: Oral mucositis is a painful condition that occurs in patients who undergo chemotherapy. Due to the worsening of oral mucositis, the patient may progress to a worse clinical condition and interrupt antineoplastic treatment. There is little literature on low-power laser therapy in chemotherapy for other solid tumors. The purpose of this study was to investigate whether low-level laser therapy (LLLT) applied before chemotherapy could prevent oral mucositis in patients with solid tumors., Methods: Laser therapy was applied at a frequency of 630nm, with a dose of 2J / cm2, for the prevention of oral mucositis induced by chemotherapy specifically for non-hematological tumors. Epidemiological data, total neutrophils, general side effects, development of oral mucositis and degree, and the performance of low-power laser therapy to prevent oral mucositis were collected. The involvement of oxidative stress was evaluated by the enzyme superoxide dismutase (SOD) through blood samples, before and after chemotherapy treatments., Results: LLLT in the proposed protocol is efficient in reducing the development of oral mucositis (only at grade I/II) in patients under chemotherapy and able to reduce the severity of oral mucosal lesions, in patients who developed mucositis after the use of the laser for prevention. All individuals who underwent LLLT protocol did not show a significant reduction of SOD activity after the last chemotherapy cycle., Conclusions: The prophylactic laser therapy protocol proposed by the study, defined at a frequency of 630nm, a dose of 2J / cm2, demonstrated the ability to decrease the occurrence of oral mucositis in patients undergoing chemotherapy protocols to solid tumors. This effect could be related to preserved SOD activity, as it was observed that oral mucositis is related to leukopenia and reduced SOD activity and LLLT protocol prevented the decrease of SOD activity.

e-Health may enhance self-management of pelvic floor muscle training (PFMT) to treat stress urinary incontinence (SUI). It is crucial to involve patients in planning, developing and monitoring the optimal e-Health solution. This research aims to describe patient-centered innovation in an early developmental stage of the WOMEN-UP solution. We conducted a qualitative study through a self-developed questionnaire in 22 women with SUI, to define system requirements from a patient's perspective. The first prototype of the WOMEN-UP solution was developed. It was tested by 9 patients in a usability study (think-aloud protocol and retrospective interviews). Patient preferences regarding the possible use of an e-Health solution with serious games for PFMT were: (1) to receive feedback about PFMT; (2) convenient home-use; (3) increasing motivation; (4) available in medical centers. Identified usability aids (31) reassured our design-development plan, which considered the biofeedback and serious games as key factors. Patient's perspective detected some unexpected issues related to the calibration and serious games, involving a change in the ongoing development to get an improved WOMEN-UP solution; the value of patient-centered innovation during the development of an e-Health solution for PFMT (WOMEN-UP solution). To identify patients' unmet needs, we proposed a longitudinal approach for the future eHealth-related patient-centered innovations.

Sixty moderately curved canals of mandibular molars classified as Vertucci's type IV canal configuration were selected by micro-CT 1174. The teeth were divided into two groups according to the kinematics used, whether reciprocating or rotary motion (n=30, totaling 60 mesial root canals). The instruments used to perform the glide path procedures had identical features (0.15 mm of tip size, 0.04 mm/mm taper, thermal treatment, and square cross-section), but differed in the direction of the cutting blade. The duration of the procedure and the absolute and percentage frequency of the instruments to reach the full working length were recorded. The torsional test (3630-1; 1992) was performed on both used and unused instruments, to evaluate a possible reduction in the torsional resistance when using the glide path procedure. Statistical analysis was performed using the unpaired t-test and the chi-square test, and the level of significance was set at 5%. The type of kinematics used affected the duration of glide path procedures, and the reciprocating motion seemed to induce less torsional stress during glide path procedures.

This study aimed to evaluate the influence of large apical preparations with Reciproc (REC), Hyflex CM (HCM) and Twisted File Adaptive (TFA) systems using micro-computed tomography (MCT). Ninety mesiobuccal (MB) and distobuccal (DB) root canals of maxillary molars (n = 45) were scanned using MCT before and after the shaping procedures. The root canals (n = 15) were prepared until REC 40.06, HCM 40.04 and TFA 35.04. The root canal transportation (RCT), centring ability (CA), change in volume of the root canal and at different levels (VC), remaining dentine thickness (RDT), removal of dentine wall (RDW) and working time (WT) were evaluated. Data were analysed using the Kruskal-Wallis and Dunn tests, and the one-way ANOVA and Tukey tests with a level of significance set at 5%. No significant difference among the instruments was found regarding the RCT, CA, RDT, RDW and WT (P > 0.05), in larger apical preparations in curved MB and straight DB canals of maxillary molars., (© 2020 Australian Society of Endodontology Inc.)

Resveratrol, a potent antioxidant, can be an alternative semen extender constituent to protect spermatozoa against reactive oxygen species (ROS); however, effects on sperm quality post-thawing and sperm function is not well understood. This study, therefore, was conducted to investigate effects of resveratrol supplementation to semen extender on sperm quality post-thawing. Bull semen was cryopreserved using extenders not supplemented or supplemented with 0.05, 0.1, or 1 mM resveratrol. Supplementation of extender with resveratrol at 0.05 mM resulted in greater (P < 0.05) sperm progressive motility, average path velocity, straight linear velocity, linearity and straightness when compared with no or 1 mM supplementations. Furthermore, effects of 0.05 mM resveratrol supplementations on plasma membrane and acrosome integrity and sperm fertilization capacity using in vitro procedures were investigated. Supplementation of semen extender with resveratrol resulted in a greater (P < 0.05) proportion of frozen-thawed spermatozoa with an intact acrosome and plasma membrane. Results from in vitro fertilization studies indicated there were no differences (P> 0.05) when there was no supplementation or supplementation with 0.05 mM resveratrol on embryo development to the cleavage and blastocyst stages. In conclusion, addition of resveratrol to bull semen extender resulted in greater sperm quality post-thawing in a dose-dependent manner, with values for variables related to sperm quality being greater when there was resveratrol supplementation at the 0.05 mM concentration. Proportion of embryo developing to the cleavage and blastocyst stages after in vitro fertilization was not affected by resveratrol supplementation to semen extenders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Stroke is the principal cause of disability around the world and the ensuing functional dependence (FD) can be correlated with different factors., Objective: To determine how demographic factors and clinical characteristics after stroke distinguish patients who achieve functional independence from those who do not., Design and Setting: Observational study at specialized neurovascular clinic in Alagoas, Brazil., Methods: FD was classified according to the modified Rankin scale (mRs): 0 to 2 points were classified as independent (FD-), and 3 to 5 points were classified as dependent (FD+). Logistic regression analysis included age, sedentary lifestyle, the Center for Epidemiological Studies - Depression Scale (CES-D) and the National Institutes of Health Stroke Scale (NIHSS). The Mann-Whitney test and χ2 test were used to compare groups., Results: We included 190 stroke patients with a mean age of 60.02 ± 14.22 years. We found that 34.8% of the patients were classified as FD+. Lower NIHSS and CES-D scores were more associated with achieving functional independence. Most of the patients had access to physical therapy, and the mean duration of rehabilitation therapy was 65.2 minutes per week. Females had higher prevalence of depressive symptoms (P = 0.005) and rehabilitation time was shorter for hemorrhagic stroke (P = 0.02)., Conclusion: We found a FD rate four times greater than in another Brazilian study. Lower stroke severity and fewer depressive symptoms were associated with achieving functional independence. Less than half of the patients were referred to a rehabilitation service at hospital discharge and few had access to multidisciplinary treatment.

Objectives: to know how people with tuberculosis undergoing treatment exercise their rights throughout daily life while experiencing illness., Methods: this qualitative study was developed from April to May 2015, with people with tuberculosis undergoing treatment in an outpatient clinic of the Municipal Tuberculosis Control Program in the city of Pelotas. Data were collected through semi-structured interviews and verified by content analysis, under the thematic modality., Results: people announced aspects that involved human rights pertaining to their experiences, and they had difficulties to achieve full rights to dignity, health, social security, and social services. Such rights were neither guaranteed by the State nor by their families., Final Considerations: it is necessary for health professionals and services to inform and equip people with tuberculosis, directly or indirectly, for the full exercise of their rights.

Epoxide hydrolases (EHs) have been characterized and engineered as biocatalysts that convert epoxides to valuable chiral vicinal diol precursors of drugs and bioactive compounds. Nonetheless, the regioselectivity control of the epoxide ring opening by EHs remains challenging. Alp1U is an α/β-fold EH that exhibits poor regioselectivity in the epoxide hydrolysis of fluostatin C (compound 1) and produces a pair of stereoisomers. Herein, we established the absolute configuration of the two stereoisomeric products and determined the crystal structure of Alp1U. A Trp-186/Trp-187/Tyr-247 oxirane oxygen hole was identified in Alp1U that replaced the canonical Tyr/Tyr pair in α/β-EHs. Mutation of residues in the atypical oxirane oxygen hole of Alp1U improved the regioselectivity for epoxide hydrolysis on 1. The single site Y247F mutation led to highly regioselective (98%) attack at C-3 of 1, whereas the double mutation W187F/Y247F resulted in regioselective (94%) nucleophilic attack at C-2. Furthermore, single-crystal X-ray structures of the two regioselective Alp1U variants in complex with 1 were determined. These findings allowed insights into the reaction details of Alp1U and provided a new approach for engineering regioselective epoxide hydrolases., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Zhang et al.)

Objective: Adaptive changes in DHEA and sulfated-DHEA (DHEAS) production from adrenal zona reticularis (ZR) have been observed in normal and pathological conditions. Here we used three different cohorts to assess timing differences in DHEAS blood level changes and characterize the relationship between early blood DHEAS reduction and cell number changes in women ZR., Materials and Methods: DHEAS plasma samples (n = 463) were analyzed in 166 healthy prepubertal girls before pubarche (<9 years) and 324 serum samples from 268 adult females (31.9-83.8 years) without conditions affecting steroidogenesis. Guided by DHEAS blood levels reduction rate, we selected the age range for ZR cell counting using DHEA/DHEAS and phosphatase and tensin homolog (PTEN), tumor suppressor and cell stress marker, immunostaining, and hematoxylin stained nuclei of 14 post-mortem adrenal glands., Results: We confirmed that overweight girls exhibited higher and earlier DHEAS levels and no difference was found compared with the average European and South American girls with a similar body mass index (BMI). Adrenopause onset threshold (AOT) defined as DHEAS blood levels <2040 nmol/L was identified in >35% of the females >40 years old and associated with significantly reduced ZR cell number (based on PTEN and hematoxylin signals). ZR cell loss may in part account for lower DHEA/DHEAS expression, but most cells remain alive with lower DHEA/DHEAS biosynthesis., Conclusion: The timely relation between significant reduction of blood DHEAS levels and decreased ZR cell number at the beginning of the 40s suggests that adrenopause is an additional burden for a significant number of middle-aged women, and may become an emergent problem associated with further sex steroids reduction during the menopausal transition.

The aim of this study was to evaluate the influence of different coronal preflaring protocols (absent, conservative and conventional) on the accuracy of Root ZX II, Raypex 6, and RomiApex A-15 electronic foramen locators (EFLs). Twenty mandibular molars with Vertucci's type IV mesial roots were subjected to endodontic exploration and foraminal patency confirmation. Under 16x magnification, its real lengths (RL) were measured and registered (RL1). The canals were then irrigated with 2.5% sodium hypochlorite and electronically measured (EM1) employing the alginate model; all measurements were performed in triplicate by a blind operator using adjusted endodontic hand-files introduced until the apex foramen. Coronal preflaring procedures were sequentially performed with #25/.06 (conservative) and #25/.12 (conventional) instruments; new RLs extents were performed after each coronal preparation protocol (RL2/RL3), as same as electronic measurements (EM2/EM3). The devices error (mm) was evaluated considering the difference between RLs and EMs at each preparation stage; their precision was stablished adopting ±0.5 mm as tolerance margin. The EFLs error significantly reduced after conventional coronal preflaring protocol (p<0.05), which not occur after the conservative one. The best precisions values were noted after conventional preparation as 90% (Root ZX II), 97.5% (Raypex 6), and 92.5% (RomiApex A-15). No significant differences were found in EFLs comparisons, regardless of the coronal protocol tested (p>0.05). Under the conditions tested it can be concluded that the EFLs evaluated were precise. Moreover, the preflaring protocols influences its accuracy's, where the less conservative one produced the best results.

The dynamics of dengue transmission are multifactorial and involve socioeconomic, ecological, and environmental aspects, the latter being closely related to local climatic conditions that affect the vector's reproductive cycle. Climate depends in turn on tropical oceanic mechanisms such as phases of El Niño/La Niña over the Pacific. The study contributes to this discussion and reports on the correlations between the Multivariate ENSO Index (MEI) in the Pacific and the number of reported dengue cases in seven state capitals in the Brazilian Amazon from 2001 to 2012. The study also analyzes the seasonality pattern (quarterly mean values) in dengue cases throughout the region. Evidence that El Niño/La Niña causes a decrease versus increase in the local rainfall pattern is consistent with the lower versus higher number of reported dengue cases in most of the state capitals in the Amazon, a result proven by the statistically significant negative correlations seen in Manaus (Amazonas), São Luís (Maranhão), Belém (Pará) and Palmas (Tocantins). The 12-years means (2001-2012) revealed the presence of pronounced seasonality in dengue incidence in the majority of the state capitals, with sharp peaks from January to March [Rio Branco (Acre), Manaus, Belém and Palmas] and from April to June (São Luís), corresponding to 50-70% of the annual total. State capitals farther north [Boa Vista (Roraima) and Macapá (Amapá)] showed dengue reporting in all quarters of the year, with no pronounced seasonality.

The aim of the present study was to assess the penetration capacity of two endodontic cements, Endosequence BC Sealer and AH Plus, in artificial lateral canals. Twenty-six two-rooted, maxillary first premolars were instrumented to size 40.06 using K3 files. In each root, six lateral canals of two diameters (0.06 and 0.10 mm) were created with a working length of 2, 4, and 6 mm. The specimens were randomly divided into two groups according to the endodontic cement to be used (Endosequence BC Sealer and AH Plus) and obturated by the single-cone technique. The specimens were imaged by digital periapical radiography and scores from 0 to 4 were attributed according to the degree of penetration by sealers into the lateral canals. Data were analyzed statistically by Kruskal-Wallis and Student-Newman-Keuls tests, and a significance level of p < 0.05 was adopted. No significant difference was observed between the two endodontic cements used to fill the simulated lateral canals (p > 0.05). The diameter of lateral canals only influenced the capacity of the Endosequence BC Sealer in filling the canals, and presented greater penetration in the lateral canals of diameter 0.10 mm (p < 0.05). We concluded that the bioceramic endodontic cement Endosequence BC Sealer presented similar ability as AH Plus to fill simulated lateral canals.

Chronic stimulation of the β-adrenergic sympathetic system induces vascular dysfunction which is associated with increased inflammatory cytokines production. A recently proposed therapy to control vascular injury through inflammatory processes involves inhibition of the enzyme dipeptidyl peptidase-IV (DPP4). The present study investigates whether the inhibition of DPP4 prevents the increase in inflammatory markers induced by isoproterenol and restores endothelial function in vivo and in vitro. Male Wistar rats were divided into four groups: vehicle (VHC), an isoproterenol-treated group (ISO), a sitagliptin-treated group (SITA), and an isoproterenol and sitagliptin-treated group (ISO + SITA). The ISO group exhibited significantly increased contractile responses to phenylephrine associated with reduced endothelial participation, which was totally prevented by DPP4 inhibition. In vitro incubation with isoproterenol had no effect on vascular smooth muscle cells, however isoproterenol increased the activity of DPP4 and the expression of inflammatory cytokines in endothelial cells, while sitagliptin reduced the level of cytokines to basal level. In conclusion, we have shown that beta-adrenergic receptor activation can increase DPP4 activity, which was associated with vascular dysfunction and cytokine expression in endothelial cells. The important role of DPP4 was further supported by sitagliptin, which reversed vascular changes induced by isoproterenol in vivo and in vitro., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The scope of this article is to describe the food consumption and eating behavior of quilombola and non-quilombola adolescents from the rural area of Southwest Bahia. A cross-sectional study with 390 adolescents aged 10 to 19 years was conducted in 2015, using an adapted PeNSE and PNS questionnaire. Food consumption was assessed by the frequency of healthy and unhealthy food markers in the previous 7 days. Eating breakfast was used as a marker of healthy eating behavior and having meals while watching TV as being unhealthy. Frequency distribution was carried out and the differences between quilombola and non-quilombola groups were assessed using the chi-square test. The prevalence ratio (PR) estimated the association of food consumption and eating behavior and the variables of interest. Low fruit consumption (30.8%), vegetables (44.3%) and milk (24.4%) was observed. Comparison between the groups revealed lower consumption of vegetables (PR = 0.73), fruit (PR = 0.67) and milk (PR = 0.68) among quilombola than among non-quilombola adolescents. Public policies targeted at nutritional assistance specific to rural adolescents are recommended, since bad eating habits can prevail throughout life and lead to poor health conditions.

The present article problematizes the incorporation of masculinities as a dimension to propel management strategies within the Brazilian National Policy of Comprehensive Men's Health Care (PNAISH). A close reading of masculinities as perceived through their intersectional character may contribute to improving the present context of review of this policy, especially considering that sociocultural characteristics that are essentially Brazilian, such as social inequality and racism, are directly associated with the high morbidity and mortality rates affecting black, young, and poor men as a result of urban violence. It becomes clear that the discourses that view men as subjects that seek health care services only in the presence of worsening symptoms do not recognize the role of social markers of difference, such as social class and race, in producing health inequities. Intersectionality provides a view of health care access as dependent on the territory where men move and on the (social, political) means that influence the recognition of men as rightful subjects. Given that certain masculinities are invisible within the arena of public health care policies, a deeper reading regarding masculinity and health is proposed from a post-structuralist perspective, as a means of thinking and doing men's health. Finally, the article also describes aspects that are essential for the review of the guidelines and policies aimed at this population., Competing Interests: Conflitos de interesse. Nada declarado pelos autores.

Mycobacterium kansasii is an opportunistic pathogen and one of the most commonly encountered species in individuals with lung disease. We here report the complete genome sequence of 12 clinical isolates of M. kansasii from patients with pulmonary disease in Brazil.

Lomaiviticin A and difluostatin A are benzofluorene-containing aromatic polyketides in the atypical angucycline family. Although these dimeric compounds are potent antitumor agents, how nature constructs their complex structures remains poorly understood. Herein, we report the discovery of a number of fluostatin type dimeric aromatic polyketides with varied C-C and C-N coupling patterns. We also demonstrate that these dimers are not true secondary metabolites, but are instead derived from non-enzymatic deacylation of biosynthetic acyl fluostatins. The non-enzymatic deacylation proceeds via a transient quinone methide like intermediate which facilitates the subsequent C-C/C-N coupled dimerization. Characterization of this unusual property of acyl fluostatins explains how dimerization takes place, and suggests a strategy for the assembly of C-C and C-N coupled aromatic polyketide dimers. Additionally, a deacylase FlsH was identified which may help to prevent accumulation of toxic quinone methides by catalyzing hydrolysis of the acyl group.

The aim of this study was to investigate salivary levels of TGFβ1 and proliferation/ maturation of epithelial mucosa cells in diabetic and hypertensive patients., Design: in this cross-sectional study, whole stimulated saliva and oral mucosa exfoliative cytology specimens were collected from 39 patients that were healthy (control, n=10) or presented history of arterial hypertension (HAS, n=9), diabetes mellitus (DM, n=10) or both (DM+HAS, n=10). Salivary flow rate (SFR), TGFβ1 level in saliva, AgNORs and the epithelial maturation were evaluated. Non-parametric Kruskal-Wallis test, followed by Dunn's multiple comparison post-test and the Spearman test correlation analysis were used. SFR showed a significant decreased in DM and DM+HAS (0.47±0.11 and 0.64±0.43 mL/min) when compared to control (1.4±0.38 mL/min). DM+HAS presented the highest value of TGFβ1 concentration (24.72±5.89 pg/mL). It was observed a positive correlation between TGFβ1 and glycaemia (R=0.6371; p<0.001) and a negative correlation between TGFβ1 and saliva (R=-0.6162; p<0.001) and glycaemia and SFR (R=-0.5654; P=0.001). AgNORs number and status of maturation of mucosa cells were similar for all conditions. DM and DM+HAS presented the lowest SFR, which correlated with increased TGFβ1 levels. Despite the higher TGFβ1 secretion it was not observed changes in the morphology or proliferation of epithelial cells when diabetes or hypertension was present.

To evaluate the amount of apically extruded debris, percentage of foraminal enlargement and apical foramen (AF) deformation that occurred during root canal preparation with different reciprocation systems: Reciproc, WaveOne (M-Wire), and ProDesign R (Shape Memory Technology Wire) at two different working lengths (WLs): 0.0 and 1.0 mm beyond the AF. The AF of 120 root canals in 60 mesial roots of mandibular molars were photographed with stereomicroscope and randomly assigned into four groups: manual, Reciproc (REC), WaveOne (WO), and ProDesign R (PDR); subsequently, they were further subdivided according to the WL (n=15). Teeth were instrumented, coupled to a dual collecting chamber, and then another photograph of each AF was captured. Extrusion was analysed by determining the weight of extruded debris. Each AF diameter was measured in pre- and post-instrumentation images to determine deformation, which was analysed, and afterwards the final format of AFs was classified (circular/oval/deformed). We found no significant differences when analysing each system at different WLs. When considering each WL, REC and WO showed highest extrusion values (P<.05); for AF enlargement, differences were observed only for WO, when it was used beyond the AF; differences were observed among M-Wire groups beyond the AF (P<.05). AF deformation was observed in all groups; PDR showed the lowest AF deformation values at both WLs; M-Wire groups showed 50% strain beyond the AF. Authors concluded that beyond the apical limit, the alloy and taper are important aspects when considering extrusion and deformation.

Objective: To describe the sexual behavior and to identify associated factors in adolescents from rural communities in Bahia, Brazil., Methods: This is a cross-sectional, population-based, and household-based study, carried out in 2015 with adolescents aged 10 to 19 years. We described the variables of sexual intercourse in life and in the last 12 months, age at first intercourse, condom use and number of partners, guidance on pregnancy, AIDS, or other sexually transmitted infections, and guidance on how to get condoms. The analysis was performed for the total sample and for the quilombola and nonquilombola strata. We used Poisson regression, with robust variance, to estimate the prevalence ratios for sexual intercourse in relation to the explanatory variables., Results: A total of 390 adolescents were interviewed, of them 42.8% were quilombolas, 51.3% females, and the median age was 14.8 years. Of these adolescents, 26.4% reported sexual intercourse (28.1% quilombolas and 25.1% non-quilombolas), and the median age of the first relation was 15 years; 77.7% of them mentioned condom use in the last intercourse and more than half received guidance on pregnancy, AIDS, or other sexually transmitted infections and received no guidance on how to get free condoms. Age (PR = 1.42) and alcohol use experimentation (PR = 2.41) were positively associated with sexual intercourse after adjustment. In the quilombola stratum, age (RP = 1.37), having three or more close friends (PR = 1.37), and experimentation with alcohol (PR = 2.60) were associated. In the non-quilombola stratum, age (PR = 1.43), black persons (PR = 2.06), and alcohol use experimentation (PR = 2.68) were associated., Conclusions: Lack of information and exposure to behaviors such as alcohol use experimentation are conditions that need to be addressed in health promotion strategies and in strategies for the prevention of sexual health problems in rural adolescents. Intersectoral partnerships between education and health also need to be strengthened to promote the autonomous and safe exercise of sexuality in this population.

Recent advances in X-ray instrumentation have made it possible to measure the spectra of an essentially unexplored class of electronic states associated with double inner-shell vacancies. Using the technique of single electron spectroscopy, spectra of states in CS 2 and SF 6 with a double hole in the K-shell and one electron exited to a normally unoccupied orbital have been obtained. The spectra are interpreted with the aid of a high-level theoretical model giving excellent agreement with the experiment. The results shed new light on the important distinction between direct and conjugate shake-up in a molecular context. In particular, systematic similarities and differences between pre-edge states near single core holes investigated in X-ray absorption spectra and the corresponding states near double core holes studied here are brought out.

The effects of Mg, Zn, Cd, and Pd dications on the photophysical properties of the tetraphenylporphyrin ligand have been explored, considering the corresponding complexes and by using the density functional theory and its time-dependent extension. Results show that absorption wavelengths do not change significantly when the metal ion changes contrary to what happens to the singlet-triplet energy gaps (ΔE S-T ) and the spin-orbit matrix elements ΨSnHsoΨTm. The most probable intersystem spin crossing (ISC) pathways for the population of the lowest triplet states have been explored. Our findings can contribute to rationalize the available experimental data and promote the potential therapeutic use of these compounds as photosensitizers in photodynamic therapy (PDT)., Competing Interests: The authors declare no conflict of interest.