F-box receptor mediated control of substrate stability and subcellular location organizes cellular development of Aspergillus nidulans.

Fungal growth and development are coordinated with specific secondary metabolism. This coordination requires 8 of 74 F-box proteins of the filamentous fungus Aspergillus nidulans. F-box proteins recognize primed substrates for ubiquitination by Skp1-Cul1-Fbx (SCF) E3 ubiquitin RING ligases and degradation by the 26S proteasome. 24 F-box proteins are found in the nuclear fraction as part of SCFs during vegetative growth. 43 F-box proteins interact with SCF proteins during growth, development or stress. 45 F-box proteins are associated with more than 700 proteins that have mainly regulatory roles. This corroborates that accurate surveillance of protein stability is prerequisite for organizing multicellular fungal development. Fbx23 combines subcellular location and protein stability control, illustrating the complexity of F-box mediated regulation during fungal development. Fbx23 interacts with epigenetic methyltransferase VipC which interacts with fungal NF-κB-like velvet domain regulator VeA that coordinates fungal development with secondary metabolism. Fbx23 prevents nuclear accumulation of methyltransferase VipC during early development. These results suggest that in addition to their role in protein degradation, F-box proteins also control subcellular accumulations of key regulatory proteins for fungal development.

Is caffeine mouth rinsing an effective strategy to improve physical and cognitive performance? A systematic review.

The aim of this study was to perform a systematic review on the effects of caffeine mouth rinsing on physical and cognitive performance. Following a search through 4 databases, 18 studies were found meeting the inclusion criteria (15 for physical performance and 3 for cognitive performance). All selected studies found an improvement in cognitive performance with caffeine mouth rinse. Four studies found positive effects of caffeine mouthwash on physical performance when repeated during exercise, while one study detected a positive effect with a single mouthwash before exercise, but only in a fasted state. Among these studies that showed positive effects, however, three (2 for physical performance and 1 for cognitive performance) presented fair methodological quality. There was also a variety of methodological approaches in the studies that showed no improvement in physical performance with caffeine mouth rinse, which may have influenced the potential to detect the ergogenic effect of caffeine mouth rinse. Thus, the effects of caffeine mouth rinse on physical performance are mixed, but a potential ergogenic effect might be present in a fasted state and when mouthwash is repeated during exercise. Concerning cognitive performance, caffeine mouth rinse seems to be a beneficial strategy.

Vaterite microparticle-loaded methylene blue for photodynamic activity in macrophages infected with Leishmania braziliensis.

Calcium carbonate (CaCO3) exhibits a variety of crystalline phases, including the anhydrous crystalline polymorphs calcite, aragonite, and vaterite. Developing porous calcium carbonate microparticles in the vaterite phase for the encapsulation of methylene blue (MB) as a photosensitizer (PS) for use in photodynamic therapy (PDT) was the goal of this investigation. Using an adsorption approach, the PS was integrated into the CaCO3 microparticles. The vaterite microparticles were characterized by scanning electron microscopy (SEM) and steady-state techniques. The trypan blue exclusion method was used to measure the biological activity of macrophages infected with Leishmania braziliensis in vitro. The vaterite microparticles produced are highly porous, non-aggregated, and uniform in size. After encapsulation, the MB-loaded microparticles kept their photophysical characteristics. The carriers that were captured allowed for dye localization inside the cells. The results obtained in this study indicated that the MB-loaded vaterite microparticles show promising photodynamic activity in macrophages infected with Leishmania braziliensis.

The High Osmolarity Glycerol Mitogen-Activated Protein Kinase regulates glucose catabolite repression in filamentous fungi.

The utilization of different carbon sources in filamentous fungi underlies a complex regulatory network governed by signaling events of different protein kinase pathways, including the high osmolarity glycerol (HOG) and protein kinase A (PKA) pathways. This work unraveled cross-talk events between these pathways in governing the utilization of preferred (glucose) and non-preferred (xylan, xylose) carbon sources in the reference fungus Aspergillus nidulans. An initial screening of a library of 103 non-essential protein kinase (NPK) deletion strains identified several mitogen-activated protein kinases (MAPKs) to be important for carbon catabolite repression (CCR). We selected the MAPKs Ste7, MpkB, and PbsA for further characterization and show that they are pivotal for HOG pathway activation, PKA activity, CCR via regulation of CreA cellular localization and protein accumulation, as well as for hydrolytic enzyme secretion. Protein-protein interaction studies show that Ste7, MpkB, and PbsA are part of the same protein complex that regulates CreA cellular localization in the presence of xylan and that this complex dissociates upon the addition of glucose, thus allowing CCR to proceed. Glycogen synthase kinase (GSK) A was also identified as part of this protein complex and shown to potentially phosphorylate two serine residues of the HOG MAPKK PbsA. This work shows that carbon source utilization is subject to cross-talk regulation by protein kinases of different signaling pathways. Furthermore, this study provides a model where the correct integration of PKA, HOG, and GSK signaling events are required for the utilization of different carbon sources.

Nucleus reuniens of the thalamus controls fear memory reconsolidation.

The nucleus reuniens has been shown to support the acquisition, consolidation, maintenance, destabilization upon retrieval, and extinction of aversive memories. However, the direct participation of this thalamic subregion in memory reconsolidation is yet to be examined. The present study addressed this question in contextually fear-conditioned rats. Post-reactivation infusion of the GABAA receptor agonist muscimol, the glutamate N2A-containing NMDA receptor antagonist TCN-201, or the protein synthesis inhibitor anisomycin into the NR induced significant impairments in memory reconsolidation. Administering muscimol or TCN-201 and anisomycin locally, or associating locally infused muscimol or TCN-201 with systemically administered clonidine, an α2-receptor adrenergic agonist that attenuates the noradrenergic tonus associated with memory reconsolidation, produced no further reduction in freezing times when compared with the muscimol-vehicle, TCN-201-vehicle, vehicle-anisomycin, and vehicle-clonidine groups. This pattern of results indicates that such treatment combinations produced no additive/synergistic effects on reconsolidation. It is plausible that NR inactivation and antagonism of glutamate N2A-containing NMDA receptors weakened/prevented the subsequent action of anisomycin and clonidine because they disrupted the early stages of signal transduction pathways involved in memory reconsolidation. It is noteworthy that these pharmacological interventions, either alone or combined, induced no contextual memory specificity changes, as assessed in a later test in a novel and unpaired context. Besides, omitting memory reactivation precluded the impairing effects of muscimol, TCN-201, anisomycin, and clonidine on reconsolidation. Together, the present findings demonstrate interacting mechanisms through which the NR can regulate contextual fear memory restabilization.

Are Demethylation Inhibitor Plus Quinone Outside Inhibitor Fungicide Premixes During Flowering Worthwhile for Fusarium Head Blight Control in Wheat? A Meta-Analysis.

Fusarium head blight (FHB), caused mainly by Fusarium graminearum, is best controlled with demethylation inhibitor (DMI) fungicides during flowering. However, the use of premixes of DMI and quinone outside inhibitor (QoI) fungicides to control FHB has increased in Brazil. Data on FHB severity and wheat yields measured in field experiments conducted in Brazil were gathered from both peer- and nonpeer-reviewed sources published from 2000 to 2018. After selection criteria were applied, 73 field trials from 35 bibliographic sources were identified, among which 50% of the data were obtained from cooperative network trials conducted after 2011. To be included in the analysis, DMI plus QoI premixes or tebuconazole were tested in at least 14 trials and 3 years. Four premixes met the criteria. Estimates of percent control (and respective 95% confidence intervals) by a network model fitted to the log of the treatment means ranged from 44.1% (pyraclostrobin plus metconazole applied once; 32.4 to 53.7) to 64.3% (pyraclostrobin plus metconazole; 58.4 to 69.3); the latter did not differ from tebuconazole (59.9%; 53.6 to 65.3). Yield response was statistically similar for pyraclostrobin plus metconazole (532.1 kg/ha; 441 to 623) and trifloxystrobin plus prothioconazole (494.9 kg/ha; 385 to 551), and both differed statistically from a group composed of tebuconazole (448.2 kg/ha; 342 to 554), trifloxystrobin plus tebuconazole (468.2 kg/ha; 385 to 551), azoxystrobin plus tebuconazole (462.4 kg/ha; 366 to 558), and pyraclostrobin plus metconazole applied once (413.7 kg/ha; 308 to 518). The two categories of FHB index (7% cutoff) and yield (3,000 kg/ha cutoff), both in the nontreated check, did not explain the heterogeneity in the estimates. Considering only the fungicide effects on yield, two sequential sprays of tebuconazole or one spray of pyraclostrobin plus metconazole as management choices are likely more profitable than DMI plus QoI premixes sprayed twice during flowering.

Thalamic nucleus reuniens regulates fear memory destabilization upon retrieval.

The neural circuit supporting aversive memory destabilization after retrieval includes the hippocampus, amygdala, and medial prefrontal cortex. The nucleus reuniens (NR) contributes to the functional interaction of these brain regions relevant to cognitive processing. However, the direct participation of this thalamic subregion in memory destabilization is yet to be investigated. The present study addressed this question in contextually fear-conditioned rats. Pre-reactivation infusion of the GABAA receptor agonist muscimol, the protein degradation inhibitor clasto-lactacystin ß-lactone (ß-lac), or the glutamate N2B-containing NMDA receptors antagonist ifenprodil into the NR prevented the post-reactivation amnestic effects of both locally infused anisomycin and systemically administered clonidine. In either case, the results suggest a significant disruption in memory destabilization. It is noteworthy that these pharmacological interventions induced no changes in expression or contextual specificity of the memory. Moreover, omitting memory reactivation precluded the muscimol, ß-lac, and ifenprodil effects on destabilization and the anisomycin and clonidine effects on reconsolidation. We also quantified the Egr1/Zif268-expressing neurons to investigate the effects of muscimol-induced NR inactivation on the activity-related plasticity locally, and in other brain regions supporting fear memory destabilization-reconsolidation. Relative to controls, there were reduced values in the NR, the dorsal CA1 hippocampus, the prelimbic cortex, and the infralimbic cortex. In contrast, increases happened in the ventral CA1 hippocampus and the basolateral amygdala. These results suggest that NR has a circuit-level influence on this process. Together, present findings demonstrate how the NR can regulate contextual fear memory destabilization upon retrieval.

Biofilm formation by Candida albicans is inhibited by photodynamic antimicrobial chemotherapy (PACT), using chlorin e6: increase in both ROS production and membrane permeability.

Candida albicans is an opportunistic fungal producing both superficial and systemic infections in immunocompromised patients. Furthermore, it has been described an increase in the frequency of infections which have become refractory to standard antifungal therapy. Photodynamic antimicrobial chemotherapy (PACT) is a potential antimicrobial therapy that combines visible light and a nontoxic dye, known as a photosensitizer, producing reactive oxygen species (ROS) that can kill the treated cells. The objective of this study was to investigate the effects of PACT, using chlorin e6, as a photosensitizer on C. albicans. In this work, we studied the effect of PACT on both cell growth and biofilm formation by C. albicans. In addition, both ROS production and cell permeability were determined after PACT. PACT inhibited both growth and biofilm formation by C. albicans. We have also observed that PACT increased both ROS production (six times) and cell membrane permeability (five times) in C. albicans. PACT decreased both cell growth and biofilm development. The effect of PACT using chlorin e6 on C. albicans could be associated with an increase in ROS production, which could increase cell permeability, producing permanent damage to the cell membranes, leading to the cell death.

Mitogen activated protein kinases SakA(HOG1) and MpkC collaborate for Aspergillus fumigatus virulence.

Here, we investigated which stress responses were influenced by the MpkC and SakA mitogen-activated protein kinases of the high-osmolarity glycerol (HOG) pathway in the fungal pathogen Aspergillus fumigatus. The ΔsakA and the double ΔmpkC ΔsakA mutants were more sensitive to osmotic and oxidative stresses, and to cell wall damaging agents. Both MpkC::GFP and SakA::GFP translocated to the nucleus upon osmotic stress and cell wall damage, with SakA::GFP showing a quicker response. The phosphorylation state of MpkA was determined post exposure to high concentrations of congo red and Sorbitol. In the wild-type strain, MpkA phosphorylation levels progressively increased in both treatments. In contrast, the ΔsakA mutant had reduced MpkA phosphorylation, and surprisingly, the double ΔmpkC ΔsakA had no detectable MpkA phosphorylation. A. fumigatus ΔsakA and ΔmpkC were virulent in mouse survival experiments, but they had a 40% reduction in fungal burden. In contrast, the ΔmpkC ΔsakA double mutant showed highly attenuated virulence, with approximately 50% mice surviving and a 75% reduction in fungal burden. We propose that both cell wall integrity (CWI) and HOG pathways collaborate, and that MpkC could act by modulating SakA activity upon exposure to several types of stresses and during CW biosynthesis.

In vitro evaluation of photodynamic therapy using curcumin on Leishmania major and Leishmania braziliensis.

Cutaneous leishmaniasis is an infectious disease caused by the Leishmania protozoan. The conventional treatment is long-lasting and aggressive, in addition to causing harmful effect. Photodynamic therapy has emerged as a promising alternative treatment, which allows local administration with fewer side effects. This study investigated the photodynamic activity of curcumin on Leishmania major and Leishmania braziliensis promastigote. Both species were submitted to incubation with curcumin in serial dilutions from 500 µg/ml up to 7.8 µg/ml. Control groups were kept in the dark while PDT groups received a fluency of 10 J/cm(2) at 450 nm. Mitochondrial activity was assessed by MTT assay 18 h after light treatment, and viability was measured by Trypan blue dye exclusion test. Morphological alterations were observed by Giemsa staining. Confocal microscopy showed the uptake of curcumin by both tested Leishmania species. Mitochondrial activity was inconclusive to determine viability; however, Trypan blue test was able to show that curcumin photodynamic treatment had a significant effect on viability of parasites. The morphology of promastigotes was highly affected by the photodynamic therapy. These results indicated that curcumin may be a promising alternative photosensitizer, because it presents no toxicity in the dark; however, further tests in co-culture with macrophages and other species of Leishmania should be conducted to determine better conditions before in vivo tests are performed.

Root-Knot Nematodes (Meloidogyne spp.) Parasitizing Resistant Tobacco Cultivars in Southern Brazil.

Our study surveyed Meloidogyne spp. from tobacco cultivars in Brazil carrying the Rk gene, which confers resistance to Meloidogyne incognita races 1 and 3. Identification of Meloidogyne populations from 39 tobacco fields was based on the analysis of esterase phenotypes, perineal patterns, and 18S-internal transcribed spacer (ITS)1-5.8S ribosomal RNA sequences. Biometric characterization and differential host tests of isolates were determined as well. We detected M. incognita, M. javanica, M. enterolobii, M. arenaria, and M. inornata in 18 (46.2%), 16 (41%), 10 (25.6%), 2 (5.1%), and 1 (2.6%) samples, respectively. Mixtures of species were found in 25.6% of the samples. This is the first report of M. inornata parasitizing tobacco in Brazil's southern region. Two morphological and biochemically unusual populations had host ranges and ITS1 sequences nearly identical to M. enterolobii and M. incognita, respectively. Pathogenic and biometric intraspecific variations were observed. Based on our results and considering the limited efficiency of the Rk gene, it is indispensable not only to search for resistance sources to M. incognita virulent strains but also to consider resistance to M. enterolobii, M. inornata, M. arenaria, and M. javanica in tobacco breeding programs. Changes in integrated management procedures should be considered to avoid increased crop damage in the future.

Prospective policy analysis-a critical interpretive synthesis review.

Most policy analysis methods and approaches are applied retrospectively. As a result, there have been calls for more documentation of the political-economy factors central to health care reforms in real-time. We sought to highlight the methods and previous applications of prospective policy analysis (PPA) in the literature to document purposeful use of PPA and reflect on opportunities and drawbacks. We used a critical interpretive synthesis (CIS) approach as our initial scoping revealed that PPA is inconsistently defined in the literature. While we found several examples of PPA, all were researcher-led, most were published recently and few described mechanisms for engagement in the policy process. In addition, methods used were often summarily described and reported on relatively short prospective time horizons. Most of the studies stemmed from high-income countries and, across our sample, did not always clearly outline the rationale for a PPA and how this analysis was conceptualized. That only about one-fifth of the articles explicitly defined PPA underscores the fact that researchers and practitioners conducting PPA should better document their intent and reflect on key elements essential for PPA. Despite a wide recognition that policy processes are dynamic and ideally require multifaceted and longitudinal examination, the PPA approach is not currently frequently documented in the literature. However, the few articles reported in this paper might overestimate gaps in PPA applications. More likely, researchers are embedded in policy processes prospectively but do not necessarily write their articles from that perspective, and analyses led by non-academics might not make their way into the published literature. Future research should feature examples of testing and refining the proposed framework, as well as designing and reporting on PPA. Even when policy-maker engagement might not be feasible, real-time policy monitoring might have value in and of itself.

Nitrogen and Silicon Contribute to Wheat Defense's to Pyrenophora tritici-repentis, but in an Independent Manner.

Nitrogen (N) and silicon (Si) are mineral elements that have shown a reduction in the damage caused by tan spot (Pyrenophora tritici-repentis (Ptr)) in wheat. However, the effects of these elements were studied separately, and the N and Si interaction effect on wheat resistance to tan spot remains elusive. Histocytological and biochemical defense responses against Ptr in wheat leaves treated with Si (+Si) at low (LN) and high N (HN) inputs were investigated. Soil amendment with Si reduced the tan spot severity in 18% due to the increase in the leaf Si concentration (around 30%), but it was affected by the N level used. The superoxide dismutase (SOD) activity was higher in +Si plants and inoculated with Ptr, leading to early and higher H2O2 and callose accumulation in wheat leaf. Interestedly, phenylalanine ammonia-lyase (PAL) activity was induced by the Si supplying, being negatively affected by the HN rate. Meanwhile, catalase (CAT), and peroxidase (POX) activities showed differential response patterns according to the Si and N rates used. Tan spot severity was reduced by both elements, but their interaction does not evidence synergic effects in this disease's control. Wheat plants from -Si and HN and +Si and LN treatments recorded lower tan spot severity.

Fullerene-C60 and PCBM as interlayers in regular and inverted lead-free PSCs using CH3NH3SnI3: an analysis of device performance and defect density dependence by SCAPS-1D.

One of the challenges hindering the commercialization of perovskite solar cells (PSCs) is the presence of toxic metals such as lead in their composition. Simulation studies using SCAPS-1D have already been conducted on lead-free PSCs to find optimized solar cell parameters, having tin as the primary candidate for replacing lead in perovskites. Here, we used fullerene-C60 and its derivative PCBM as interlayers in a lead-free tin-based PSC between the ETL (ZnO) and the perovskite MASI in both regular and inverted configurations of PSCs using SCAPS-1D software. To the best of our knowledge, this is the first simulation study reporting the impact of using fullerene-C60 and PCBM as interlayers in lead-free PSCs. The defect density (Nt) of the perovskite material is varied, allowing us to observe its influence on the power conversion efficiency (PCE). Using an Nt value of 1017 cm-3 without the interlayer, the PCE was 6.90% and 3.72% for regular and inverted devices. Using PCBM as an interlayer improves the efficiency of both simulated PSCs, achieving a maximum PCE of 8.11% and 5.26% for the regular and inverted configurations, respectively. Decreasing the Nt from 1017 cm-3 to 1016 cm-3 caused a significant increase in efficiency, reaching 13.38% (n-i-p) and 10.00% (p-i-n). Finally, using the optimized parameters and an ideal Nt value (1013 cm-3), both PSCs achieved a PCE close to 30%.

Impact of secreted glucanases upon the cell surface and fitness of Candida albicans during colonisation and infection.

Host recognition of the pathogen-associated molecular pattern (PAMP), ß-1,3-glucan, plays a major role in antifungal immunity. ß-1,3-glucan is an essential component of the inner cell wall of the opportunistic pathogen Candida albicans. Most ß-1,3-glucan is shielded by the outer cell wall layer of mannan fibrils, but some can become exposed at the cell surface. In response to host signals such as lactate, C. albicans shaves the exposed ß-1,3-glucan from its cell surface, thereby reducing the ability of innate immune cells to recognise and kill the fungus. We have used sets of barcoded xog1 and eng1 mutants to compare the impacts of the secreted ß-glucanases Xog1 and Eng1 upon C. albicans in vitro and in vivo. Flow cytometry of Fc-dectin-1-stained strains revealed that Eng1 plays the greater role in lactate-induced ß-1,3-glucan masking. Transmission electron microscopy and stress assays showed that neither Eng1 nor Xog1 are essential for cell wall maintenance, but the inactivation of either enzyme compromised fungal adhesion to gut and vaginal epithelial cells. Competitive barcode sequencing suggested that neither Eng1 nor Xog1 strongly influence C. albicans fitness during systemic infection or vaginal colonisation in mice. However, the deletion of XOG1 enhanced C. albicans fitness during gut colonisation. We conclude that both Eng1 and Xog1 exert subtle effects on the C. albicans cell surface that influence fungal adhesion to host cells and that affect fungal colonisation in certain host niches.

Pyruvate decarboxylase activity is regulated by the Ser/Thr protein phosphatase Sit4p in the yeast Saccharomyces cerevisiae.

Deletion of SIT4 phosphatase decreased the pyruvate decarboxylase activity, which is essential for directing the glucose flux to ethanol production. Concomitantly, a reduction in the fermentative capacity was observed. As pyruvate decarboxylase expression was not altered, its post-translational phosphorylation was studied. Immunoblot analyses using anti-phosphoserine antibodies against the affinity-purified Pdc1p showed that Pdc1p is a phosphoenzyme. Dephosphorylation of Pdc1p by alkaline phosphatase inhibited activity by 50%. Moreover, phosphorylation of Pdc1p was dependent on the growth phase, being hyperphosphorylated in the logarithmic phase, which showed to be dependent on the presence of SIT4. A comparison of the kinetic parameters of pyruvate decarboxylase in total protein extracts from WT yeast and the Δsit4 mutant revealed that the apparent K(m) values of the cofactor thiamin pyrophosphate (TPP) were 81 and 205 µM, respectively, with V(max) values of 0.294 and 0.173 µmol mg⁻¹ min⁻¹, respectively. Treatment of the purified enzyme with alkaline phosphatase increased the K(m) for TPP from 20 to 84 µM and for pyruvate from 2.3 to 4.6 mM, while the V(max) changed from 0.806 to 0.673 µmol mg⁻¹ min⁻¹. These results suggest that the Pdc1p phosphorylation dependent on SIT4 occurs at residues that change the apparent affinity for TPP and pyruvate.

[For the sacrifice of isolation: leprosy and philanthropy in Argentina and Brazil, 1930-1946]. / Em prol do sacrifício do isolamento: lepra e filantropia na Argentina e no Brasil, 1930-1946.

Patronato de Leprosos, in Argentina, and Federação das Sociedades de Assistência aos Lázaros e Defesa Contra a Lepra, in Brazil, were created as institutions designed to help people with leprosy and their families. Headed by women from the ruling classes, these entities took very similar actions, despite the different national contexts in which they operated, both supplementing leprosy healthcare policies in their respective countries. This article aims to demonstrate the similarities in the strategies adopted by both philanthropic institutions, which, in the 1930s and 1940s, acted in harmony with the physicians who supported compulsory isolation.

Adsorption of phosphate from aqueous solution by hydrous zirconium oxide.

Synthetic ZrO2 x nH2O was used for phosphate removal from aqueous solution. The optimum adsorbent dose obtained for phosphate adsorption on to hydrous zirconium oxide was 0.1 g. The kinetic process was described very well by a pseudo-second-order rate model. The phosphate adsorption tended to increase with the decrease in pH. The adsorption capacity increased from 61 to 66 mg g(-1) when the temperature was increased from 298 to 338 K. A phosphate desorption of approximately 74% was obtained using water at pH 12.

Prevalence of Tinnitus in Patients Diagnosed with Cerebral Arteriovenous Fistula Treated with Endovascular Technique.

Introduction Tinnitus is characterized as the conscious and involuntary perception of sound, and it affects ∼ 30% of the population. Despite careful physical examination, the etiology of tinnitus can be established for only 30% of patients. Tinnitus is a common symptom of cerebral arteriovenous fistulas and results from increased blood flow through the dural venous sinuses, leading to turbulent arterial flow, mainly related to sigmoid and transverse sinus lesions. Objectives To analyze the frequency of tinnitus, patient profile, and endovascular treatment characteristics in individuals diagnosed with cerebral arteriovenous fistulas. Methods A retrospective and observational study based on reviewed data from medical records on the PHILIPS Tasy system (Philips Healthcare, Cambridge, MA, USA) at the neurosurgery and interventional neuroradiology service of Hospital Santa Isabel in Blumenau-state of Santa Catarina, Brazil. Results The profile of 68 individuals diagnosed with cerebral arteriovenous fistula who underwent endovascular treatment were analyzed. Most patients were female, aged 31 to 60. Tinnitus affected 18 individuals. Dural fistulas were the most prevalent in the sample, and computed tomography alone was the most used diagnostic method for initial investigation. Conclusion The prevalence of this symptom in patients diagnosed with cerebral arteriovenous fistula was found in 26.5% of this sample, mainly in women with associated comorbidities. Tinnitus remission was observed in all patients who underwent endovascular treatment to correct cerebral fistula.

Hydroalcoholic extract of Remijia ferruginea accelerates the closure of skin wounds by modulating tissue morphology and antioxidant profile: An in vitro and in vivo study.

ETHNOPHARMACOLOGICAL RELEVANCE: Remijia ferruginea DC. (Rubiaceae) (syn. Cinchona ferruginea A.St.-Hil.) is used in traditional medicine for the treatment of wounds, fever and malaria. AIM: This study investigated in vitro the proliferative and antioxidant effects of hydroalcoholic extract of leaves of R. ferruginea (HERF) and in vivo the healing effect of ointment based on HERF. MATERIALS AND METHODS: The plant extract was characterized by liquid chromatography/mass spectrometry. Cell proliferation assays and in vitro antioxidant activity were performed. In in vivo assays, wound contraction ax was evaluated, as well as histological analyzes such as cellularity, proportion of blood vessels and collagen type I and III index. In addition, analyzes of the antioxidant enzymes SOD, CAT and GST were performed. RESULTS: Our results showed in the chromatographic analysis that catechin, rutin and quercetin were the main phenolic compounds in the plant extract and may be responsible for the antioxidant and proliferative effects (p < 0.05). In addition, these compounds were found in higher concentration in leaves collected in spring. The ointment containing HERF was able to modulate tissue morphology, increasing cell proliferation, blood vessels, being able to stimulate the production of collagen fibers type I and III, (p < 0.05) contributing to scar tissue maturation and resistance. CONCLUSION: Our findings indicated that the three doses of HERF tested (1%, 3% and 5%) can modulate the skin repair process, but the best effects were observed after exposure to the highest dose.