Search

Chagas disease has spread throughout the world mainly because of the migration of infected individuals. In Brazil, only benznidazole (Bnz) is used; however, it is toxic and not active in the chronic phase, and cases of resistance are described. This work aimed at the synthesis and the trypanocidal evaluation in vitro and in vivo of six new Bnz analogues (3-8). They were designed by exploring the bioisosteric substitution between the amide group contained in Bnz and the 1,2,3-triazole ring. All the compounds were synthesized in good yields. With the exception of compound 7, the in vitro biological evaluation shows that all Bnz analogues were active against the amastigote form, whereas only compounds 3, 4, 5, and 8 were active against trypomastigote. Compounds 4 and 5 showed the most promising activities in vitro against the form of trypomastigote, being more active than Bnz. In vivo evaluation of compounds, 3-8 showed lower potency and higher toxicity than Bnz. Although the 1,2,3-triazole ring has been described in the literature as an amide bioisostere, its substitution here has reduced the activity of the compounds and made them more toxic. Thus, further molecular optimization could provide novel therapeutic agents for Chagas' disease., (© 2018 John Wiley & Sons A/S.)

Sexual dimorphism has been proposed as one of the facial traits to have evolved through sexual selection and to affect attractiveness perception. Even with numerous studies documenting its effect on attractiveness and mate choice, the neurophysiological correlates of the perception of sexual dimorphism are not yet fully understood. In the present study, event-related potentials (ERPs) were recorded during visualisation of faces that had been previously transformed in shape to appear more masculine or more feminine. The participants' task consisted of judging the attractiveness of half of the total number of faces, and performing a sex discrimination task on the other half. Both early and late potentials were modulated by the sex of faces, whereas the effect of the sexually dimorphic transform was mainly visible in the P2 (positive deflection around 200 ms after stimulus onset), EPN (early posterior negativity) and LPP (late positive potential) components. There was an effect of sexual dimorphism on P2 and EPN amplitudes when female participants visualised male faces, which may indicate that masculinity is particularly attended to when viewing opposite sex members. Also, ERP results seem to support the idea of sex differences in social categorisation decisions regarding faces, although differences were not evident on behavioural results. In general, these findings contribute to a better understanding of how humans perceive sexually dimorphic characteristics in other individuals' faces and how they affect attractiveness judgements., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background The consumption of addictive substances is common in adolescence and raises concerns about future addiction. We investigated addictive substance consumption among young people to inform the design of drug intervention programmes. Methods Participants were a population-based sample of 14- to 24-year-olds from Paredes, northern Portugal. A self-report questionnaire measured social and health variables, including tobacco, alcohol and illicit drug consumption. Results Data were analysed for 731 valid responses. Participants who had drunk alcohol did so first at 14.7 years (mean); 15.3% (95% confidence intervals [CI]: 12.9-18.1) drank alcohol regularly (more than 1/week, adjusted for age and sex) (95% CI: 12.9-18.1). Participants who had smoked tobacco did so first at 14.8 years (mean); 16.6% (95% CI: 14.0-19.5) were regular smokers. Illicit drug consumption was reported by 16.7% of participants (95% CI: 14.2-19.6) and 10.4% consumed drugs regularly. Conclusion We found a high prevalence of addictive substance consumption, particularly alcohol. As cultural attitudes likely influence alcohol consumption, a multigenerational approach is needed to address adolescent consumption. Participants' main sources of drug information were family members. Strategies are needed to promote drug literacy in parents and other relatives to change adolescents' culturally acquired habits of addictive substance consumption.

Executive control and its modulation of attentional mechanisms allow us to detect and adapt to conflicting information. According to recent studies, executive control functions may be modulated by unconsciously perceived information, although the available evidence is not consistent. In this study, we used a Flanker Task and employed Chromatic Flicker Fusion, a suppression technique that has been proposed as more adequate to elicit executive control functions, to assess conflict and conflict adaptation effects. Our results showed that, when suppressed, flankers did not evoke conflict related effects on performance. However, in trials where most flankers were incongruent, longer response times in congruent trials were observed, consistent with orienting responses. Our results help to support earlier theories regarding the inherent limitations of unconsciously perceived information, though future studies should further investigate why and under which conditions is the executive control system modulated by unconscious information., (Copyright © 2018 Elsevier Inc. All rights reserved.)

After a stroke in middle cerebral artery territory, there is a high probability of dysfunction of the ventromedial pathways, mainly related with postural control mechanisms such as the anticipatory postural adjustments (APAs). According to neuroanatomical knowledge, these pathways have a predominant ipsilesional disposition, which justifies a bilateral postural control dysfunction, often neglected in rehabilitation. In order to assess this bilateral postural control dysfunction, electromyography activity was assessed in eight post-stroke and 10 healthy individuals in the anterior deltoids, the superior and lower trapezius, and the latissimus dorsi as they reached for a bottle with both upper limbs separately at a self-selected velocity and fast velocity while standing associated with trunk kinematics analysis. Through this analysis it was possible to compare the timing of APAs in scapular muscles between sides in post-stroke and with healthy individuals, and to verify if there is a relation between the timing and the displacement of the trunk in the temporal window of the APAs. Indeed, post-stroke individuals show a delayed activation of APAs on scapular girdle muscles on both ipsilesional and contralesional sides, which were not reflected in the trunk displacement.

Many studies have indicated that the chemical cues from body odors (BOs) of donors experiencing negative emotions can influence the psychophysiological and behavioral response of the observers. However, these olfactory cues have been used mainly as contextual information for processing visual stimuli. Here, for the first time, we evaluate how emotional BO affects the emotional tone of a subsequent BO message. Axillary sweat samples were taken from 20 donors in 3 separate sessions while they watched fear, disgust, or neutral videos. In a double-blind experiment, we assessed the cardiac and subjective responses from 69 participants who were either exposed to negative emotional or neutral BOs. Our results showed a reduced cardiac parasympathetic activity (HF%)-indicating increased stress-when participants smelled the emotional BOs before the neutral BOs, compared to when they smelled neutral followed by emotional BOs. The intensity of the neutral odor also increased following the exposure to both negative BOs. These findings indicate that BOs contain an emotion-dependent chemical cue that affects the perceiver both at the physiological and subjective levels.

This article explores the significance of parasport culture in highlighting an emancipatory understanding of difference and enhancing social empowerment. Disability studies are used to illuminate the influence of ableist ideology on people with impairments. Rather than being suppressed, difference should be recognized and valued in parasport practices and ideologies, leading to a pluralist culture, in which farther and wider social emancipation can be grounded. Acceptance of difference is an absolute and essential precondition for parasport cultures to promote positive social change for people with disabilities., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

American trypanosomiasis or Chagas disease (CD) is a vector borne pathology caused by the parasite Trypanosoma cruzi (T. cruzi), which remains a serious global health problem. The current available treatment for CD is limited to two nitroderivatives with limited efficacy and several side effects. The rational design of ergosterol synthetic route inhibitors (e.g. CYP51 inhibitors) represents a promising strategy for fungi and trypanosomatids, exhibiting excellent anti-T.cruzi activity in pre-clinical assays. In the present work, we evaluate through different approaches (molecular docking, structure activity relationships, CYP51 inhibitory assay, and phenotypic screenings in vitro and in vivo) the potency and selectivity of a novel CYP51 inhibitor (compound 1) and its analogues against T.cruzi infection. Regarding anti-parasitic effect, compound 1 was active in vitro with EC 50 3.86 and 4.00 μM upon intracellular (Tulahuen strain) and bloodstream forms (Y strain), respectively. In vivo assays showed that compound 1 reduced in 43% the parasitemia peak but, unfortunately failed to promote animal survival. In order to promote an enhancement at the potency and pharmacological properties, 17 new analogues were purchased and screened in vitro. Our findings demonstrated that five compounds were active against intracellular forms, highlighting compounds 1e and 1f, with EC 50 2.20 and 2.70 μM, respectively, and selectivity indices (SI) = 50 and 36, respectively. Against bloodstream trypomastigotes, compound 1f reached an EC 50 value of 20.62 μM, in a similar range to Benznidazole, but with low SI (3). Although improved the solubility of compound 1, the analogue 1f did not enhance the potency in vitro neither promote better in vivo efficacy against mouse model of acute T.cruzi infection arguing for the synthesis of novel pyrazolo[3,4-e][1,4]thiazepin derivatives aiming to contribute for alternative therapies for CD., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Trypanosoma cruzi is the etiological agent of Chagas disease, a public health challenge due to its morbidity and mortality rates, which affects around 6-7 million people worldwide. Symptoms, response to chemotherapy, and the course of Chagas disease are greatly influenced by T. cruzi's intra-specific variability. Thus, DNA mutations in this parasite possibly play a key role in the wide range of clinical manifestations and in drug sensitivity. Indeed, the environmental conditions of oxidative stress faced by T. cruzi during its life cycle can generate genetic mutations. However, the lack of an established experimental design to assess mutation rates in T. cruzi precludes the study of conditions and mechanisms that potentially produce genomic variability in this parasite. We developed an assay that employs a reporter gene that, once mutated in specific positions, convert G418-sensitive into G418-insenstitive T. cruzi. We were able to determine the frequency of DNA mutations in T. cruzi exposed and non-exposed to oxidative insults assessing the number of colony-forming units in solid selective media after plating a defined number of cells. We verified that T. cruzi's spontaneous mutation frequency was comparable to those found in other eukaryotes, and that exposure to hydrogen peroxide promoted a two-fold increase in T. cruzi's mutation frequency. We hypothesize that genetic mutations in T. cruzi can arise from oxidative insults faced by this parasite during its life cycle.

Therapies for human African trypanosomiasis and Chagas disease, caused by Trypanosoma brucei and Trypanosoma cruzi , respectively, are limited, providing minimal therapeutic options for the millions of individuals living in very poor communities. Here the effects of 10 novel quinolines are evaluated in silico and by phenotypic studies using in vitro and in vivo models. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties revealed that most molecules did not infringe on Lipinski's rules, which is a prediction of good oral absorption. These quinolines showed high probabilities of Caco2 permeability and human intestinal absorption and low probabilities of mutagenicity and of hERG1 inhibition. In vitro screens against bloodstream forms of T. cruzi demonstrated that all quinolines were more active than the reference drug (benznidazole [Bz]), except for DB2171 and DB2192, with five (DB2187, DB2131, DB2186, DB2191, and DB2217) displaying 50% effective concentrations (EC 50 s) of <3 μM (4-fold lower than that of Bz). Nine quinolines were more effective than Bz (2.7 μM) against amastigotes, showing EC 50 s ranging from 0.6 to 0.1 μM. All quinolines were also highly active in vitro against African trypanosomes, showing EC 50 s of ≤0.25 μM. The most potent and highly selective candidates for each parasite species were tested in in vivo models. Results for DB2186 were promising in mice with T. cruzi and T. brucei infections, reaching a 70% reduction of the parasitemia load for T. cruzi , and it cured 2 out of 4 mice infected with T. brucei DB2217 was also active in vivo and cured all 4 mice (100% cure rate) with T. brucei infection., (Copyright © 2018 American Society for Microbiology.)

Five bis-arylimidamides were assayed as anti- Trypanosoma cruzi agents by in vitro , in silico , and in vivo approaches. None were considered to be pan-assay interference compounds. They had a favorable pharmacokinetic landscape and were active against trypomastigotes and intracellular forms, and in combination with benznidazole, they gave no interaction. The most selective agent (28SMB032) tested in vivo led to a 40% reduction in parasitemia (0.1 mg/kg of body weight/5 days intraperitoneally) but without mortality protection. In silico target fishing suggested DNA as the main target, but ultrastructural data did not match., (Copyright © 2018 American Society for Microbiology.)

Persistent cognitive activity is an important factor in disturbing sleep-onset both during bedtime and when attempting to get back to sleep after nocturnal awakenings. One of the most specific self-report measures designed to assess this feature is the Glasgow Content of Thoughts Inventory (GCTI). In this study, we investigated the preliminary psychometric properties of GCTI in a large sample of higher education European Portuguese students (N = 2995). Our results suggest that there is evidence of good internal consistency (α = 0.93) and validity indicators. Moreover, we found an interpretable factorial structure comprising 5 correlated factors that needs to be confirmed in future studies. The European Portuguese version of the GCTI appears to be a reliable and valid instrument for measurement of sleep-onset disturbing cognitions.

Background: Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. This illness is found mainly in 21 Latin American countries and an estimated 8 million people are infected worldwide. The unsatisfactory chemotherapy provokes severe toxicity and resistant strains. Medicinal plants constitute a promising source of new drugs and remedies against all kinds of disorders, mainly infectious diseases arousing interest worldwide., Objective: The aim of this study is the isolation, structural identification and evaluation of the trypanocidal activity of samples present in the Excoecaria lucida Sw. leaves., Methods: Total extract (TE) of E. lucida Sw. leaves was obtained by ethanol extract therefore fractionated sequentially with hexane, ethyl acetate and n-butanol, to obtain three phases: Hex, EA and But, respectively. Ellagic acid (EL1) was purified from both EA and But phases, while EL2; a 1:1 stigmasterol-3-O-β-D-glucopyranoside plus sitosterol-3-O-β-D-glucopyranoside mixture was obtained from the Hex phase. Activity assays were performed using bloodstream and intracellular forms of T. cruzi and cytotoxicity assays using L929 fibroblasts., Results: The EL1 and EL2 samples were more active against bloodstream trypomastigote forms with EC50 of 53.0±3.6 and 58.2±29.0 µg/mL, respectively; at 100 µg/mL. These samples also showed 70% of inhibition of L929 cells infection. Toxicity assays demonstrated that after 96 h of treatment only the fractions Hex and EA presented detectable cytotoxicity., Conclusion: Ellagic acid, stigmasterol-3-O-β-D-glucopyranoside and sitosterol-3-O-β-Dglucopyranoside are reported for the first time in E. lucida Sw. leaves as well as their biological activity studies supporting further investigations for Chagas disease treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

In this work, we studied theoretically the formation process of a molecularly imprinted polymer (MIP) for dinotefuran (DNF), testing distinct functional monomers (FM) in various solvents through density functional theory calculations. The results revealed that the best conditions for MIP synthesis were established with methacrylic acid (MAA) as FM in a 1 : 4 stoichiometry and with chloroform as the solvent. This protocol showed the most favourable stabilization energies for the pre-polymerization complexes. Furthermore, the formation of the FM/template complex is enthalpy driven and the occurrence of hydrogen bonds between the DNF and MAA plays a major role in the complex stability. To confirm the theoretical results, MIP was experimentally synthesized considering the best conditions found at the molecular level and characterized by scanning electron microscopy and thermogravimetric analysis. After that, the synthesized material was efficiently employed in microextraction by packed sorbent combined with high-performance liquid chromatography in a preliminary study of the recovery of DNF from water and artificial saliva samples.

Introduction Effective ventilation during cardiopulmonary resuscitation (CPR) is essential to reduce morbidity and mortality rates in cardiac arrest. Hyperventilation during CPR reduces the efficiency of compressions and coronary perfusion. Problem How could ventilation in CPR be optimized? The objective of this study was to evaluate non-invasive ventilator support using different devices., Methods: The study compares the regularity and intensity of non-invasive ventilation during simulated, conventional CPR and ventilatory support using three distinct ventilation devices: a standard manual resuscitator, with and without airway pressure manometer, and an automatic transport ventilator. Student's t-test was used to evaluate statistical differences between groups. P values <.05 were regarded as significant., Results: Peak inspiratory pressure during ventilatory support and CPR was significantly increased in the group with manual resuscitator without manometer when compared with the manual resuscitator with manometer support (MS) group or automatic ventilator (AV) group., Conclusion: The study recommends for ventilatory support the use of a manual resuscitator equipped with MS or AVs, due to the risk of reduction in coronary perfusion pressure and iatrogenic thoracic injury during hyperventilation found using manual resuscitator without manometer. Lacerda RS , de Lima FCA , Bastos LP , Vinco AF , Schneider FBA , Coelho YL , Fernandes HGC , Bacalhau JMR , Bermudes IMS , da Silva CF , da Silva LP , Pezato R . Benefits of manometer in non-invasive ventilatory support. Prehosp Disaster Med. 2017;32(6):615-620.

Metronidazole (Mtz) is a commercial broad-spectrum nitroimidazolic derivative with relevant antimicrobial activity and relative safety profile. Therefore, it is fair to consider Mtz a candidate for drug repurposing for other neglected conditions such as Chagas disease (CD), a parasitic pathology caused by Trypanosoma cruzi. CD is treated only with benznidazole (Bz) and nifurtimox, both introduced in clinics decades ago despite important limitations, including low efficacy on the later disease stage (chronic form) and severe side effects. New cheap and fast alternative treatments for CD are needed, thus the repurposing of Mtz was assessed in vitro and in vivo in mono- and combined therapy. In vitro assays demonstrated EC 50 >200µM for Mtz, while for Bz the values ranged from 2.51µM (intracellular forms) to 11.5µM (bloodstream trypomastigotes). When both drugs were combined in fixed-ratio proportions, Mtz promoted Bz potency (lower EC 50 values). In vivo toxicity assays for Mtz in mice showed no adverse effects neither histopathological alterations up to 2000mg/kg. Regarding experimental T. cruzi infection, Bz 100mg/kg suppressed parasitemia while Mtz (up to 1000mg/kg) in monotherapy did not, but prolonged animal survival at 250 and 500 regimen doses. The combination of both drugs (Bz 10+Mtz 250) prevented mortality (70%) besides protected against electric cardiac alterations triggered by the parasite infection. Although not able to reduce parasite load, the combination therapy prevented animal mortality; this was possibly due to a protection of the electric cardiac physiology that is normally altered in experimental infection of T. cruzi. It also suggested that the interaction with Mtz could have improved the pharmacokinetics of Bz. Our study emphasizes the importance of drug repurposing and combined therapy for CD to contribute to alternative therapies for this neglected and silent pathology., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Cultivable microbiota presents in a coffee semi-dry processing wastewater treatment plant (WTP) was identified. Thirty-two operational taxonomic units (OTUs) were detected, these being 16 bacteria, 11 yeasts and 4 filamentous fungi. Bacteria dominated the microbial population (11.61 log CFU mL - 1 ), and presented the highest total diversity index when observed in the WTP aerobic stage (Shannon = 1.94 and Simpson = 0.81). The most frequent bacterial species were Enterobacter asburiae, Sphingobacterium griseoflavum, Chryseobacterium bovis, Serratia marcescens, Corynebacterium flavescens, Acetobacter orientalis and Acetobacter indonesiensis; these showed the largest total bacteria populations in the WTP, with approximately 10 log CFU mL - 1 . Yeasts were present at 7 log CFU mL - 1 of viable cells, with Hanseniaspora uvarum, Wickerhamomyces anomalus, Torulaspora delbrueckii, Saturnispora gosingensis, and Kazachstania gamospora being the prevalent species. Filamentous fungi were found at 6 log CFU mL - 1 , with Fusarium oxysporum the most populous species. The identified species have the potential to act as a biological treatment in the WTP, and the application of them for this purpose must be better studied.

Soil sorption of insecticides employed in agriculture is an important parameter to probe the environmental fate of organic chemicals. Therefore, methods for the prediction of soil sorption of new agrochemical candidates, as well as for the rationalization of the molecular characteristics responsible for a given sorption profile, are extremely beneficial for the environment. A quantitative structure-property relationship method based on chemical structure images as molecular descriptors provided a reliable model for the soil sorption prediction of 24 widely used organophosphorus insecticides. By means of contour maps obtained from the partial least squares regression coefficients and the variable importance in projection scores, key molecular moieties were targeted for possible structural modification, in order to obtain novel and more environmentally friendly insecticide candidates. The image-based descriptors applied encode molecular arrangement, atoms connectivity, groups size, and polarity; consequently, the findings in this work cannot be achieved by a simple relationship with hydrophobicity, usually described by the octanol-water partition coefficient., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The association between sleep quality and quality of life (QoL) in clinical samples diagnosed with sleep disorders, mental disorders, or other medical conditions has been widely investigated. However, few studies focused on this relationship in samples of mostly young and healthy adults. This study analyzed the associations between sleep quality and several dimensions of QoL in higher education students and examined whether or not sleep quality would significantly predict QoL after statistically controlling for psychopathological symptoms., Design: Observational and transversal., Setting: Non-clinical; higher education., Participants: A sample of 324 college students, aged 17 to 47 years (M=20.89±2.85) were enrolled., Measurements: European Portuguese versions of the Pittsburgh Sleep Quality Index (PSQI), the WHOQOL-Bref to measure QoL, and the Brief Symptom Inventory (BSI) to measure psychopathological symptoms., Results: All PSQI components were significantly associated with general QoL and the psychological and physical QoL domains. The subjective sleep quality and daytime dysfunction PSQI components were consistently associated with all WHOQOL-Bref domains and general QoL. Hierarchical regression analyses further showed that the PSQI components as a whole, and in particular subjective sleep quality, added significant contributions to the general QoL facet and to the psychological, physical, and environmental QoL domains, after controlling for psychopathological symptoms., Conclusions: Several components of sleep quality and different facets/domains of QoL are associated in higher education students, particularly subjective sleep quality, which remains a significant predictor of most aspects of QoL, regardless of the presence of psychopathological symptoms., (Copyright © 2017 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: The purpose of this study was to understand the reasons and quantify the number of ultrasounds and computed tomographies that are potentially wasted in the hospital emergency in our institution, and the importance that the radiologist can have in the management and screening of these exams., Material and Methods: It was decided that urgent tests that were pending for more than seven days would be the object of analysis as to why they were not performed, consulting the electronic medical records. Six causes were used to cancel the requests: 'Changing the patient's status', 'Patient's withdrawal, refusal or abandonment', 'Patient's death'; 'No criteria or contraindicated', 'Lack of human resources' and 'Mistaken request'., Results: In the year 2015 we obtained 1211 canceled exams, since they were pending more than a week ago. The first four causes totaled 602 exams (sum of 283, 94, 41 and 184). The last two, 609 (sum of 29 and 580)., Discussion: It was verified that the 602 exams corresponding to the sum of the first four causes reflected a potential waste in clinical tests since they were not determinant in the approach of the Emergency episode nor on the final destiny of the patient. Under the tip of the iceberg may exist further examinations and patients who have not escaped inadequate or unjustified examinations., Conclusion: The radiologist can better manage the required radiological examinations, effectively screening within a multidisciplinary team environment, promoting the development and supporting the respect of guidelines, and potentially reducing requests through opinions or second opinions.

In this work, an efficient pipette tip based on molecularly imprinted polymers solid-phase extraction (PT-MIP-SPE) method was developed for carvedilol (CAR) analysis. This compound is available in clinical practice as a racemic mixture, in which (-)-(S)-CAR is a β- and α 1 -adrenergic antagonist, while (+)-(R)-CAR only acts as an α 1 -adrenergic antagonist. Enantioseparation of CAR presented satisfactory retention times (5.85 and 14.84min), acceptable theoretical plates (N=2048 and 2018) and good resolution (Rs=9.27). The separation was performed using a Chiralpak ® IA column (100mm×4.6mm, 3μm), a mixture of methanol:ethanol:water (64:15:21, v/v/v) plus 0.3% diethylamine as mobile phase, temperature of 35°C and flow rate of 1.5mLmin -1 . After density functional theory calculations based on prepolymerization complexes, the best protocol for the MIP synthesis was chosen. Then, some parameters that affect the PT-MIP-SPE technique were investigated. After optimization, the best conditions were 300μL of water as washing solvent, 500μL of acetonitrile:acetic acid (7:3, v/v) as eluting solvent, 20mg of MIP, 500μL of urine sample (pH 12.5) and no addition of NaCl. Recoveries±relative standard deviation (RSD%) for (+)-(R)-CAR and (-)-(S)-CAR were 101.9±4.8% and 104.6±2.1%, respectively. The method was linear over the concentration range from 20 to 1280ngmL -1 for each enantiomer, with correlation coefficients larger than 0.99 for both enantiomers. The method was applied successfully in a preliminary study of urinary excretion after administration of CAR racemate to a healthy volunteer., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Antimicrobial resistance is a current public health concern, limiting the available therapeutic options used for the treatment of common bacterial infections. The development of new drug entities via biotechnological processes is however expensive and time-consuming. Therefore, old antimicrobial agents have been recovered for clinical use. An example of these drugs is polymyxin, which is known for its serious adverse side effects, such as nephrotoxicity, neurotoxicity and promotion of skin pigmentation. To overcome these limitations, the use of biodegradable nanoparticles has been proposed to allow site-specific targeting, increasing the drug's bioavailability and decreasing its side effects. The aim of this work was the development of an optimized pharmaceutical formulation composed of solid lipid nanoparticles (SLN) loading polymyxin B sulphate (PLX) for the treatment of bacterial infections. The PLX-loaded SLN were produced by a double emulsion method (w/o/w), obtaining particles with a mean size of approximately 200nm, polydispersity of 0.3 and zeta potential of -30mV. The encapsulation efficiency reached values above 90% for all developed formulations. SLN remained stable for a period of 6months of storage at room temperature. The occlusive properties of the SLN was shown to be dependent on the type of lipid, while the antimicrobial properties of PLX-loaded SLN were effective against resistant strains of Pseudomonas aeruginosa. Results from the differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and small angle X-ray scattering (SAXS) analyses confirmed the crystallinity of the inner SLN matrices, suggesting the capacity of these particles to modify the release profile of the loaded drug., (Copyright © 2017. Published by Elsevier B.V.)

Aim: This study evaluated whether anethole attenuates the inflammatory response and joint damage in a model of adjuvant-induced arthritis (AIA) in rats., Methods: The animals were treated with 62.5-, 125-, or 250-mg/kg anethole daily for 21 days after AIA and necropsied on days 14 and 21 to evaluate the number of serum and synovial leukocytes (total and differential), serum cytokines (IL-2, IL-6, IL-12, IL-17, and TNF-α), and nitric oxide concentrations. Morphologic changes in the cartilage and bone of the femorotibial articulation in both left paw and right paw were studied in hematoxylin/eosin and Sirius Red-hematoxylin sections., Results: Different doses of anethole suppressed paw swelling and the number of serum and synovial leukocytes. However, 250 mg/kg of anethole more effectively controlled local and systemic inflammation. Histological evaluation revealed significant prevention of cartilage damage and inflammatory infiltrate scores. Morphometric analysis showed pannus formation, the thickness of the articular cartilage, and bone resorption lower in the anethole-treated AIA group compared to untreated AIA group on both days 14 and 21. These significant anti-inflammatory effects in the anethole-treated AIA group were associated with downregulation of cytokines and nitric oxide levels., Conclusion: Therefore, anethole may be a useful intervention to treat inflammatory arthritis.

Objective: To assess performance of TIRADS classification on a prospective surgical cohort, demonstrating its clinical usefulness., Methods: Between June 2009 and October 2012, patients assessed with pre-operative ultrasound (US) were included in this IRB-approved study. Nodules were categorised according to our previously described TIRADS classification. Final pathological diagnosis was obtained from the thyroidectomy specimen. Sensitivity, specificity, positive/negative predictive values and likelihood ratios were calculated., Results: The study included 210 patients with 502 nodules (average: 2.39 (±1.64) nodules/patient). Median size was 7 mm (3-60 mm). Malignancy was 0 % (0/116) in TIRADS 2, 1.79 % (1/56) in TIRADS 3, 76.13 % (185/243) in TIRADS 4 [subgroups: TIRADS 4A 5.88 % (1/17), TIRADS 4B 62.82 % (49/78), TIRADS 4C 91.22 % (135/148)], and 98.85 % (86/87) in TIRADS 5. With a cut-off point at TIRADS 4-5 to perform FNAB, we obtained: sensitivity 99.6 % (95 % CI: 98.9-100.0), specificity 74.35 % (95 % CI: 68.7-80.0), PPV 82.1 % (95 % CI: 78.0-86.3), NPV 99.4 % (95 % CI: 98.3-100.0), PLR 3.9 (95 % CI: 3.6-4.2) and an NLR 0.005 (95 % CI: 0.003-0.04) for malignancy., Conclusion: US-based TIRADS classification allows selection of nodules requiring FNAB and recognition of those with a low malignancy risk., Key Points: • TIRADS classification allows accurate selection of thyroid nodules requiring biopsy (TIRADS 4-5). • The recognition of benign/possibly benign patterns can avoid unnecessary procedures. • This classification and its sonographic patterns are validated using surgical specimens.

The sibling species of Capitella capitata are globally known for their tolerance to disturbed habitats and the C. capitata complex is often used as an ecological indicator. A recent re-description proposed that C. capitata, originally described in Greenland is restricted to the Artic and Subarctic regions. Given their ecological relevance, we conducted a morphological and molecular analyses based on mtDNA sequences to investigate the diversity and distribution of the C. capitata complex along the Brazilian coast. Our morphological and molecular data were congruent and revealed the existence of four new species distinct from C. capitata, collected from the type locality. This study is the first characterization of the biodiversity and distribution of Capitella species made along the Brazilian coast and yielded a set of morphological characters corroborated by the mtDNA sequences for species identification. Our results increase the biodiversity of the genus along the Brazilian coast by describing four new species (Capitella aracaensis sp. n., Capitella biota sp. n., Capitella neoaciculata sp. n. and Capitella nonatoi sp. n.). One species was collected from only one sampling site, while the others are distributed along the coast.

Research investigating the effect of lighting and viewpoint changes on unfamiliar and newly learnt faces has revealed that such recognition is highly image dependent and that changes in either of these leads to poor recognition accuracy. Three experiments are reported to extend these findings by examining the effect of apparent age on the recognition of newly learnt faces. Experiment 1 investigated the ability to generalize to novel ages of a face after learning a single image. It was found that recognition was best for the learnt image with performance falling the greater the dissimilarity between the study and test images. Experiments 2 and 3 examined whether learning two images aids subsequent recognition of a novel image. The results indicated that interpolation between two studied images (Experiment 2) provided some additional benefit over learning a single view, but that this did not extend to extrapolation (Experiment 3). The results from all studies suggest that recognition was driven primarily by pictorial codes and that the recognition of faces learnt from a limited number of sources operates on stored images of faces as opposed to more abstract, structural, representations.

Netto, M. S. B., Lima, W. G., Correia, K. C., da Silva, C. F. B., Thon, M., Martins, R. B., Miller, R. N. G., Michereff, S. J., and Câmara, M. P. S. 2016. Analysis of phylogeny, distribution, and pathogenicity of Botryosphaeriaceae species associated with gummosis of Anacardium in Brazil, with a new species of Lasiodiplodia. We identified Botryosphaeriaceae species associated with gummosis on Anacardium in Brazil. Isolates were sampled and identified on the basis morphology and phylogeny, through analysis of a partial translation elongation factor 1-α sequence, ribosomal DNA internal transcribed spacers, and β-tubulin gene sequence. Ten taxa were identified, namely, Lasiodiplodia brasiliense, L. euphorbicola, L. gonubiensis, L. iraniensis, L. jatrophicola, L. gravistriata sp. nov., L. pseudotheobromae, L. theobromae, Neofusicoccum batangarum, and Pseudofusicoccum stromaticum. Lasiodiplodia theobromae has been previously reported in cashew and is the most prevalent species observed. All the other species are reported here for the first time on this host. All species of Botryosphaeriaceae were pathogenic on detached green cashew shoots. Differences in aggressiveness were observed among the species, with N. batangarum, L. iraniensis, L. jatrophicola, and L. gravistriata characterized as the most aggressive species, whilst L. euphorbicola and L. pseudotheobromae were identified as the least aggressive., (Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

The electrocardiogram (ECG) signal has been widely used to study the physiological substrates of emotion. However, searching for better filtering techniques in order to obtain a signal with better quality and with the maximum relevant information remains an important issue for researchers in this field. Signal processing is largely performed for ECG analysis and interpretation, but this process can be susceptible to error in the delineation phase. In addition, it can lead to the loss of important information that is usually considered as noise and, consequently, discarded from the analysis. The goal of this study was to evaluate if the ECG noise allows for the classification of emotions, while using its entropy as an input in a decision tree classifier. We collected the ECG signal from 25 healthy participants while they were presented with videos eliciting negative (fear and disgust) and neutral emotions. The results indicated that the neutral condition showed a perfect identification (100%), whereas the classification of negative emotions indicated good identification performances (60% of sensitivity and 80% of specificity). These results suggest that the entropy of noise contains relevant information that can be useful to improve the analysis of the physiological correlates of emotion., (© 2016 Society for Psychophysiological Research.)

Chagas disease is a life-threatening infection caused by a variety of genetically diverse strains of the protozoan parasite Trypanosoma cruzi The current treatment (benznidazole and nifurtimox) is unsatisfactory, and potential alternatives include inhibitors of sterol 14α-demethylase (CYP51), the cytochrome P450 enzyme essential for the biosynthesis of sterols in eukaryotes and the major target of clinical and agricultural antifungals. Here we performed a comparative investigation of two protozoon-specific CYP51 inhibitors, VNI and its CYP51 structure-based derivative VFV, in the murine models of infection caused by the Y strain of T. cruzi The effects of different treatment regimens and drug delivery vehicles were evaluated in animals of both genders, with benznidazole serving as the reference drug. Regardless of the treatment scheme or delivery vehicle, VFV was more potent in both genders, causing a >99.7% peak parasitemia reduction, while the VNI values varied from 91 to 100%. Treatments with VNI and VFV resulted in 100% animal survival and 0% natural relapse after the end of therapy, though, except for the 120-day treatment schemes with VFV, relapses after three cycles of immunosuppression were observed in each animal group, and quantitative PCR analysis revealed a very light parasite load in the blood samples (sometimes below or near the detection limit, which was 1.5 parasite equivalents/ml). Our studies support further investigations of this class of compounds, including their testing against other T. cruzi strains and in combination with other drugs., (Copyright © 2017 American Society for Microbiology.)

A recent study claimed face skin color as a sexually dimorphic variable that influences attractiveness preferences in mate choice. Thereby, skin color may assume the role of a mate quality signal influencing attractiveness preferences. As body odor is linked to attractiveness, this study aimed to explore whether the odors of men with more masculine facial skin color would be evaluated more positively than odors from less masculine men. Female raters were presented with body odors of 18 men and were asked to rate them in various characteristics. Multilevel modeling revealed that the odors of the donors with more masculine color were rated not only as more attractive, more pleasant, and sexier, but also healthier. This indicates that odor associated with men with more masculine skin color is attractive, just as other sexually dimorphic traits. Furthermore, we found a negative relation between skin color masculinity and perceived odor maleness. Regarding this last finding, a new discussion is introduced with respect to the influence of cognitive stereotypes in odor judgments. Altogether, the study supports the possibility that chemosensory signals may be communicating signs of mate quality associated with masculinity., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Skin changes caused by aging increase the risk of skin damages, such as pressure ulcers, during hospitalization of elderly patients. There is few information about the cost of wound treatment in Brazil. Conversely, skin and wound problems are highly reported among hospitalized elderly patients and caregivers. The purpose is to analyze the socio-demographic and clinical profile associated with skin and wound care in hospitalized elderly., Methods: This is a prospective observational study. The sample consisted of 75 patients, aged 60 years or more, randomly selected in three hospitals in Rio de Janeiro, Brazil. Data extraction from nursing records of the sample, using cross mapping with Nursing Interventions Classification. Data Synthesis supported by SAS 6.11 (SAS Institute, Inc. Cary North Carolina) in association with SPSS version 14.0 and statistics analysis., Results: The findings were: age standard deviation 7.8, with minimum as 60, and maximum as 91 years old. Prevalence of women and married seniors. High prevalence of long-term hospitalization. There were 21 Nursing Interventions in the nursing records and seventeen of them related to skin and wound care. They were described in 57 nursing activities, present during 376 evaluations and repeated 1756 times. A significant difference was obtained between age and the presence of the nursing interventions "Positioning" (p-0.004), Eye Care/Hygiene (p- < 0.0001) and Oral Health Maintenance (p-0.0003)., Conclusion: The skin care to prevention and treatment of skin damages represented the major demand of nursing interventions in different clinical conditions of hospitalized elderly.

This study evaluated the use of vinasse as a substrate for microbial biomass production and its disposal impact on the environment. After grown in vinasse, the microbial biomass (SCP) of two Saccharomyces cerevisiae strains, CCMA 0137 and CCMA 0188, showed high levels of essential amino acids (3.78%), varying levels of chemical elements, and low nucleic acid content (2.38%), i. e, good characteristics to food supplemements. Following biological treatment, spent vinasse biochemical oxygen demand (BOD) and chemical oxygen demand (COD) decreased to 51.56 and 29.29%, respectively. Cultivation with S. cerevisiae significantly reduced short term phytotoxicity and toxicity on soil microbiota of spent vinasse., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This work aims to examine the influence of the metabolic state of the yeast Pichia kudriavzevii on the susceptibility to a metals mixture (5 mg L -1 Cd, 10 mg L -1 Pb, and 5 mg L -1 Zn). Cells exposed to the metals mixture in the presence of 25 mmol L -1 glucose displayed a higher loss of membrane integrity and proliferation capacity, compared to cells incubated in the absence of glucose. The analysis of the effect of individual metals revealed that glucose increased the toxic effect of Cd marginally, and of Pb significantly. The increased susceptibility to heavy metals due to glucose was attenuated in the simultaneous presence of a mitochondrial respiration inhibitor such as sodium azide (NaN 3 ). ATP-depleted yeast cells, resulting from treatment with the non-metabolizable glucose analogue 2-deoxy-d-glucose, showed an increased susceptibility to heavy metals mixture. Pre-incubation of yeast cells with 1 or 1.5 mmol L -1 Ca 2+ reduced significantly (P < 0.05) the loss of membrane integrity induced by the metals mixture. These findings contribute to the understanding of metals mechanisms of toxicity in the non-conventional yeast P. kudriavzevii., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We synthesized and characterized a series of oxo-centered carbonyl-triruthenium complexes with the general formula [Ru 3 O(CH 3 COO) 6 (L) 2 (CO)], where L = 2,6-dimethylpyrazine (dmpz) (1), isonicotinamide (adpy) (2), 4-acetylpyridine (acpy) (3), 3-methylpyridine (3-pic) (4), 4-methylpyridine (4-pic) (5), 4-tert-butylpyridine (4-tbpy) (6), 4-(dimethyl)aminopyridine (dmap) (7), or 4-aminopyridine (ampy) (8); we also investigated the photoreactivity of these complexes. Single-crystal X-ray diffraction helped to elucidate the structures of 1·H 2 O, 7·C 2 H 4 Cl 2 , and 8. The unit cell of 8 is composed of four cluster units; the hydrogen bonds between the amino groups of the terminal ligand of a neighboring molecule and the oxygen atoms of CO or acetate bridging ligands hold these cluster units together. The spectroscopic (NMR, UV-visible, and IR) and the electrochemical properties (cyclic voltammetry) of these complexes correlated with the ancillary ligands in terms of their σ-donating and π-accepting characteristics. The molecular orbital and the electronic localized description of the [Ru 3 O]-CO unit helped to rationalize the correlations. The photoreactivity of compounds 1-8 was investigated by laser excitation at 377 nm. Given the CO photorelease quantum yields, σ-donor ligands and aqueous medium (more polar) stabilized the charge-transfer excited state that culminated in CO photosubstitution, leading to higher Φ values.

The quest for safer anti-inflammatory drugs is still the focus of several medicinal chemistry programs. Chromones (4H-chromen-4-ones) are a group of naturally occurring compounds ubiquitous in plants, and the chromone core has proven to be a privileged scaffold in medicinal chemistry. Herein we provide an overview of the relevance of chromones as anti-inflammatory agents, specifically as inhibitors of cyclooxygenase (COX), 5-lipoxygenase (5-LOX), interleukin-5 (IL-5), and nitric oxide ( . NO) production. Numerous structure-activity relationships and mechanisms of action are discussed. This review is therefore intended to provide a foundation for the design and synthesis of novel chromone-based compound libraries for further development into safer and more efficient anti-inflammatory agents., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The phenotypic activity of two 5-nitroindazolinones, i.e. 2-benzyl-1-propyl (22) and 2-benzyl-1-butyl (24) derivatives, previously proposed as anti-Trypanosoma cruzi prototypes, was presently assayed on bloodstream trypomastigotes (BT) of the moderately drug-resistant Y strain. Further exploration of putative targets and cellular mechanisms involved in their activity was also carried out. Therefore, transmission electron microscopy, high-resolution respirometry and flow cytometry procedures were performed on BT treated for up to 24 h with the respective EC50 value of each derivative. Results demonstrated that although 22 and 24 were not as active as benznidazole in this in vitro assay on BT, both compounds triggered important damages in T. cruzi that lead to the parasite death. Ultrastructural alterations included shedding events, detachment of plasma membrane and nuclear envelope, loss of mitochondrial integrity, besides the occurrence of a large number of intracellular vesicles and profiles of endoplasmic reticulum surrounding cytoplasmic organelles such as mitochondrion. Moreover, both derivatives affected mitochondrion leading to this organelle dysfunction, as reflected by the inhibition in oxygen consumption and the loss of mitochondrial membrane potential. Altogether, the findings exposed in the present study propose autophagic processes and mitochondrial machinery as part of the mode of action of both 5-nitroindazolinones 22 and 24 on T. cruzi trypomastigotes.

The Halstead Category Test (HCT) is a neuropsychological test that measures a person's ability to formulate and apply abstract principles. Performance must be adjusted based on feedback after each trial and errors are common until the underlying rules are discovered. Event-related potential (ERP) studies associated with the HCT are lacking. This paper demonstrates the use of a methodology inspired on Singular Spectrum Analysis (SSA) applied to EEG signals, to remove high amplitude ocular and movement artifacts during performance on the test. This filtering technique introduces no phase or latency distortions, with minimum loss of relevant EEG information. Importantly, the test was applied in its original clinical format, without introducing adaptations to ERP recordings. After signal treatment, the feedback-related negativity (FRN) wave, which is related to error-processing, was identified. This component peaked around 250ms, after feedback, in fronto-central electrodes. As expected, errors elicited more negative amplitudes than correct responses. Results are discussed in terms of the increased clinical potential that coupling ERP information with behavioral performance data can bring to the specificity of the HCT in diagnosing different types of impairment in frontal brain function., (Copyright © 2016. Published by Elsevier B.V.)

Background: Stent-assisted coil embolization (SACE) is a viable therapeutic approach for wide-neck intracranial aneurysms. However, it can be technically challenging in small cerebral vessels (≤2 mm)., Objective: To present our experience with stents approved for SACE in aneurysms with small parent arteries., Methods: All patients who underwent stent-assisted aneurysm treatment with either a Neuroform or an Enterprise stent device at our institution between June 2006 and October 2012 were identified. Additionally, we evaluated each patient's vascular risk factors, aneurysm characteristics (ruptured vs non-ruptured, incidental finding, recanalized) and follow-up angiography data., Results: A total of 41 patients with 44 aneurysms met our criteria, including 31 women and 10 men. Most of the aneurysms were located in the anterior circulation (75%). Stent placement in vessels 1.2-2 mm in diameter was successful in 93.2%. Thromboembolic complications occurred in 6 cases and vessel straightening was seen in 1 case only. Initial nearly complete to complete aneurysm obliteration was achieved in 88.6%. Six-month follow-up angiography showed coil compaction in three cases, one asymptomatic in-stent stenosis and stent occlusion. Twelve to 20-months' follow-up showed stable coil compaction in two patients compared with previous follow-up, and aneurysm recanalization in two patients. Twenty-four to 36-months' follow-up showed further coil compaction in one of these patients and aneurysm recanalization in a previous case of stable coil compaction on mid-term follow-up., Conclusions: Our results suggest that SACE of aneurysms with small parent vessels is feasible in selected cases and shows good long-term patency rates of parent arteries., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Although canine identification of body odor (BO) has been widely used as forensic evidence, the concept of nosewitness identification by human observers was only recently put to the test. The results indicated that BOs associated with male characters in authentic crime videos could later be identified in BO lineup tests well above chance. To further evaluate nosewitness memory, we assessed the effects of lineup size (Experiment 1) and retention interval (Experiment 2), using a forced-choice memory test. The results showed that nosewitness identification works for all lineup sizes (3, 5, and 8 BOs), but that larger lineups compromise identification performance in similarity to observations from eye- and earwitness studies. Also in line with previous eye- and earwitness studies, but in disagreement with some studies on odor memory, Experiment 2 showed significant forgetting between shorter retention intervals (15 min) and longer retention intervals (1-week) using lineups of five BOs. Altogether this study shows that identification of BO in a forensic setting is possible and has limits and characteristics in line with witness identification through other sensory modalities.

Citrus canker, caused by the Gram-negative bacterium Xanthomonas citri subsp citri (Xac), is a major disease affecting citriculture worldwide, because of the susceptibility of the host and the lack of efficient control methods. Previous studies have reported that some genes of phytopathogenic bacteria possess a consensus nucleotide sequence (TTCGC...N15...TTCGC) designated the "plant-inducible-promoter box" (PIP box) located in the promoter region, which is responsible for activating the expression of pathogenicity and virulence factors when the pathogen is in contact with the host plant. In this study, we mapped and investigated the expression of 104 Xac genes associated with the PIP box sequences using a macroarray analysis. Xac gene expression was observed during in vitro (Xac grown for 12 or 20 h in XAM1 induction medium) or in vivo (bacteria grown in orange leaves for 3 to 5 days) infection conditions. Xac grown in non-induction NB liquid medium was used as the control. cDNA was isolated from bacteria grown under the different conditions and hybridized to the macroarray, and 32 genes differentially expressed during the infection period (in vitro or in vivo induction) were identified. The macroarray results were validated for some of the genes through semi-quantitative RT-PCR, and the functionality of the PIP box-containing promoter was demonstrated by activating b-glucuronidase reporter gene activity by the PIP box-containing promoter region during Xac-citrus host interaction.

Background: Being an adolescent mother and cohabiting with the maternal grandmother have been shown to be risk factors for a shorter breastfeeding duration. The objective of this study was to assess whether the positive effects of a pro-breastfeeding intervention aimed at adolescent mothers and maternal grandmothers on the prevalence of breastfeeding observed in the first year of life were maintained at 2 years of age., Methods: This study is the continuation of a randomized clinical trial initiated in 2006 involving 323 adolescent mothers, their newborns and maternal grandmothers when cohabiting. The intervention consisted of six breastfeeding counseling sessions, the first one held at the maternity ward and the others at the participants' homes at 7, 15, 30, 60, and 120 days postpartum. The present study reports data collected when the children were 4 to 7 years old, concerning the maintenance of breastfeeding at 2 years. Data were analyzed using multivariable Poisson regression model with robust variance, with breastfeeding at 2 years of age as the outcome., Results: Maintenance of breastfeeding for 2 years or more was present in 32.2% of the sample. When the intervention and control groups were compared, the prevalence of breastfeeding at 2 years was similar (29.9 vs. 34.3%, respectively; p = 0.605). Multivariable analysis failed to reveal an association between exposure to the intervention and maintenance of breastfeeding at 2 years in the different models tested., Conclusions: The positive impact of the intervention on the prevalence of breastfeeding observed in the first year of life was not maintained at 2 years of age., Trial Registration: The study was registered at ClinicalTrials.gov on May 28, 2009 under protocol no. NCT00910377.

The present work aims to contribute for the elucidation of the role of oxidative stress in the toxicity associated with the exposure of Pichia kudriavzevii to multi-metals (Cd, Pb and Zn). Cells of the non-conventional yeast P. kudriavzevii exposed for 6 h to the action of multi-metals accumulated intracellular reactive oxygen species (ROS), evaluated through the oxidation of the probe 2',7'-dichlorodihydrofluorescein diacetate. A progressive loss of membrane integrity (monitored using propidium iodide) was observed in multi-metal-treated cells. The triggering of intracellular ROS accumulation preceded the loss of membrane integrity. These results suggest that the disruption of membrane integrity can be attributed to the oxidative stress. The exposure of yeast cells to single metal showed that, under the concentrations tested, Pb was the metal responsible for the induction of the oxidative stress. Yeast cells coexposed to an antioxidant (ascorbic acid) and multi-metals did not accumulate intracellular ROS, but loss proliferation capacity. Together, the data obtained indicated that intracellular ROS accumulation contributed to metal toxicity, namely for the disruption of membrane integrity of the yeast P. kudriavzevii. It was proposed that Pb toxicity (the metal responsible for the toxic symptoms under the conditions tested) result from the combination of an ionic mechanism and the intracellular ROS accumulation.

Arylimidamides (AIAs) have been shown to have considerable biological activity against intracellular pathogens, includingTrypanosoma cruzi, which causes Chagas disease. In the present study, the activities of 12 novel bis-AIAs and 2 mono-AIAs against different strains ofT. cruziin vitroandin vivowere analyzed. The most active wasm-terphenyl bis-AIA (35DAP073), which had a 50% effective concentration (EC50) of 0.5 μM for trypomastigotes (Y strain), which made it 26-fold more effective than benznidazole (Bz; 13 μM). It was also active against the Colombiana strain (EC50= 3.8 μM). Analysis of the activity against intracellular forms of the Tulahuen strain showed that this bis-AIA (EC50= 0.04 μM) was about 100-fold more active than Bz (2 μM). The trypanocidal effect was dissociated from the ability to trigger intracellular lipid bodies within host cells, detected by oil red labeling. Both an active compound (35DAP073) and an inactive compound (26SMB060) displayed similar activation profiles. Due to their high selectivity indexes, two AIAs (35DAP073 and 35DAP081) were moved toin vivostudies, but because of the results of acute toxicity assays, 35DAP081 was excluded from the subsequent tests. The findings obtained with 35DAP073 treatment of infections caused by the Y strain revealed that 2 days of therapy induced a dose-dependent action, leading to 96 to 46% reductions in the level of parasitemia. However, the administration of 10 daily doses in animals infected with the Colombiana strain resulted in toxicity, preventing longer periods of treatment. The activity of the combination of 0.5 mg/kg of body weight/day 35DAP073 with 100 mg/kg/day Bz for 10 consecutive days was then assayed. Treatment with the combination resulted in the suppression of parasitemia, the elimination of neurological toxic effects, and survival of 100% of the animals. Quantitative PCR showed a considerable reduction in the parasite load (60%) compared to that achieved with Bz or the amidine alone. Our results support further investigations of this class with the aim of developing novel alternatives for the treatment of Chagas disease., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Sleep effort is generally defined as the attempt to force and induce sleep in a voluntary manner. This study aimed to document the psychometric properties of a brief measure of sleep effort--the Glasgow Sleep Effort Scale--in its European (Portuguese) version using a large sample (N = 2,995). The results supported the good internal consistency of the overall scale scores (α = .79). Potential construct validity was evaluated with various methods, including criterion validity. There was also a convergent validity indicator. Principal components analysis revealed a 1-dimensional structure that accounted for 45% of the total variance. This preliminary study suggests that this Portuguese version of the Glasgow Sleep Effort Scale is a measure of sleep behavior suitable for research and clinical purposes. However, more studies are needed, particularly with clinical groups., ((c) 2016 APA, all rights reserved).)

Objective To analyze the pathway of clinical trials of monoclonal antibodies and biological medicines for cancer treatment involving Brazilian institutions from 2003 to 2012. Method This retrospective, descriptive study was based on review of two clinical trial registries, ClinicalTrials.gov and the Brazilian registry ReBEC. Phase II or III studies with participation from Brazilian institutions listed in at least one of the registries were included. Following selection of the trials, the pathway of monoclonal antibodies and biological medicines was investigated from the research stage until licensing by the Brazilian Agency for Sanitary Surveillance (Anvisa), Food and Drug Administration (FDA), and European Medicines Agency (EMA). Results Nine trials (eight phase III and one phase II) were selected. All had a randomized, controlled design. Two trials were double-blind and seven were open-label, and all recruited adults (≥ 18 years of age) of both sexes. The mean number of patients recruited per trial was 985.2. Seven trials had been completed and two had been terminated early. All trials were sponsored by non-Brazilian pharmaceutical companies and focused on renal, colorectal, gastric, and lung (non-small cell) cancer, non-Hodgkin lymphoma, and melanoma, and involved the use of cetuximab, figitumumab, ipilimumab, rituximab, bevacizumab and interferon alfa-2a. The FDA was the first agency to license the drugs, followed by EMA, except in the case of interferon alfa-2a, which was not approved by EMA. We were unable to determine the year of drug licensing by Anvisa in Brazil. Conclusions The participation of Brazil in clinical trials of monoclonal antibodies and biological medications for cancer treatment is insufficient. The quality of the available information on trials, history of licensing, and other relevant elements is a major weakness of the sources reviewed.

Chitosan films can be used as wound dressings for the treatment of chronic wounds and severe burns. The antimicrobial properties of these films may be enhanced by the addition of silver. Despite the antimicrobial activity of silver, several studies have reported the cytotoxicity as a factor limiting its biomedical applications. This problem may, however, be circumvented by the provision of sustained release of silver. Silver zeolites can be used as drug delivery platforms to extend the release of silver. The objective of this study was to evaluate the addition of clinoptilolite and A-type zeolites in chitosan films. Sodium zeolites were initially subjected to ion-exchange in a batch reactor. Films were prepared by casting technique using a 2% w/w chitosan solution and two zeolite doses (0.1 or 0.2% w/w). Films were characterized by thermal analysis, color analysis, scanning electron microscopy, X-ray diffraction, and water vapor permeation. The results showed that films present potential for application as dressing. The water vapor permeability is one of the main properties in wound dressings, the best results were obtained for A-type zeolite/chitosan films, which presented a brief reduction of this property in relation to zeolite-free chitosan film. On the other hand, the films containing clinoptilolite showed lower water vapor permeation, which may be also explained by the best distribution of the particles into the polymer which also promoted greater thermal resistance.

This study aimed to evaluate the effect of the level of crude glycerin (CG) on in vitro fermentation kinetics (0, 20, 40, 60, and 80 g/kg DM of sugar cane silage), on in vitro neutral detergent fiber (NDF) degradation (0, 30, 60, and 90 g/kg DM of sugar cane silage), and intake and digestibility of nutrients and nitrogen balance (0, 20, 55, 82, and 108 g/kg DM of sugar cane silage) in lambs. The in vitro trials were conducted in a completely randomized design with three repetitions. The in vivo trial was conducted in a Latin square design with five repetitions (5 × 5). For variables in which the F test was considered significant, the statistical interpretation of the effect of CG substitution levels was carried out through regression analyses. Kinetic parameters were not affected by CG inclusion. On in vitro NDF degradation, a significant effect of CG levels was observed on the potentially degradable fraction of NDF, the insoluble potentially degradable fraction of NDF, and the undegradable NDF fraction. The intake and digestibility of nutrients and nitrogen balance were not affected by CG inclusion. The CG levels change in vitro NDF degradability parameters; however, there were no changes in animal intake, digestibility, and nitrogen balance with the inclusion levels used.