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The pedunculopontine nucleus (PPN) has been proposed as target for deep brain stimulation (DBS) in patients with postural instability and gait disorders due to its involvement in muscle tonus adjustments and control of locomotion. However, it is a deep-seated brainstem nucleus without clear imaging or electrophysiological markers. Some studies suggested that diffusion tensor imaging (DTI) may help guiding electrode placement in the PPN by showing the surrounding fiber bundles, but none have provided a direct histological correlation. We investigated DTI fractional anisotropy (FA) maps from in vivo and in situ post-mortem magnetic resonance images (MRI) compared to histological evaluations for improving PPN targeting in humans. A post-mortem brain was scanned in a clinical 3T MR system in situ. Thereafter, the brain was processed with a special method ideally suited for cytoarchitectonic analyses. Also, nine volunteers had in vivo brain scanning using the same MRI protocol. Images from volunteers were compared to those obtained in the post-mortem study. FA values of the volunteers were obtained from PPN, inferior colliculus, cerebellar crossing fibers and medial lemniscus using histological data and atlas information. FA values in the PPN were significantly lower than in the surrounding white matter region and higher than in areas with predominantly gray matter. In Nissl-stained histologic sections, the PPN extended for more than 10 mm in the rostro-caudal axis being closely attached to the lateral parabrachial nucleus. Our DTI analyses and the spatial correlation with histological findings proposed a location for PPN that matched the position assigned to this nucleus in the literature. Coregistration of neuroimaging and cytoarchitectonic features can add value to help establishing functional architectonics of the PPN and facilitate neurosurgical targeting of this extended nucleus.

In the present study, we examined 30 individuals of introduced African cichlids, Oreochromis niloticus and Coptodon rendalli, collected in a river spring of the Pardo River, Paranapanema River basin, southeastern Brazil. Based on morphological and molecular analyses of the partial LSU rDNA gene, we identified four species of monogeneans, Cichlidogyrus tilapiae, C. thurstonae, C. mbirizei, and Scutogyrus longicornis on the gills of O. niloticus, whereas individuals of C. rendalli were infested only with C. papernastrema. This is the first record of C. mbirizei and C. papernastrema in tilapias from Brazil. The ecological consequences of the introduction of exotic species of tilapia such as O. niloticus and C. rendalli along with their monogenean parasites in a wild environment represented by a river spring are discussed. Our new molecular data on Cichlidogyrus and Scutogyrus contribute to the investigation of the phylogenetic interrelationships of these widely distributed genera of monogeneans since their species composition is still unsettled.

Background: To determine the alterations in the corneal topography after pars planavitrectomy with the system of 20- and 25-gauge. Methods: A total of 29 patients with vitreous hemorrhage. The first group (17 patients) had to undergo a pars planavitrectomy with the 20-gauge system, whereas the second (12 patients) had the pars planavitrectomy with the 25-gauge system. The corneal topography was analyzed in the pre-operation, in the first, third, and sixth months in the post-operation. Results: the group which underwent the standartvitrectomy registered a statistically significant difference in the keratometric difference (dK) in the first month compared to the pre-operation (p < 0,000), first month with the third month (p < 0,020), first month and sixth month (p < 0,008). In the 25-gauge system group significant statistical alterations did not occur. Conclusion: astigmatism occurs in the first month post vitrectomy standard. The 25-gauge systemis notinducedastigmatism. [ABSTRACT FROM AUTHOR]

Diversity of Creptotrema was investigated using morphological and molecular tools, including data for Creptotrema creptotrema (type-species). Three new species, parasites of Brazilian fishes, are described: Creptotrema conconae n. sp. (type-host, Imparfinis mirini Haseman), Creptotrema schubarti n. sp. (type-host, Characidium schubarti Travassos) and Creptotrema megacetabularis n. sp. (type-host, Auchenipterus osteomystax (Miranda Ribeiro)). The diagnosis of the genus was amended to include new features. The new species differ from each other mainly in terms of body shape, relative sucker size, and testes position. DNA sequences were obtained from Creptotrema spp. from Brazil, including 28S, ITS and COI. Genetic divergences among the new species and C. creptotrema varied from 2.1 to 5.2% (21–49 bp) for 28S, and 6.6 to 16.4% (21–45 bp) for COI. Phylogenetic analysis (28S) placed the newly generated DNA sequences of Creptotrema in a clade (Creptotrema clade sensu stricto) composed of C. creptotrema, the new species described herein, and all species previously described as Auriculostoma, revealing that Auriculostoma is best interpreted as a synonym of Creptotrema based on the principle of priority of zoological nomenclature. Creptotrema funduli, the single sequence of the genus previously available, was not grouped within the Creptotrema clade sensu stricto, suggesting the need for reevaluation of the taxonomic status of this species. Our results showed that Creptotrema represents a monophyletic genus of trematodes widely distributed across the Americas, which currently comprises 19 valid species of parasites of teleosts and anurans.

The Dactylosomatidae Jakowska and Negrelli, 1955 are one of four families belonging to adeleorinid coccidia and comprise the genera Babesiosoma Jakowska and Nigrelli, 1956 and Dactylosoma Labbé, 1894. These blood protozoa occur in peripheral blood of lower vertebrates, and are commonly reported parasitising amphibians. The present study describes Dactylosoma piperis n. sp. from the pepper frog Leptodactylus labyrinthicus (Spix, 1824) (Anura: Leptodactylidae), collected in 2018 at the municipality of Araguaiana, Mato Grosso State, Brazil, based on morphology of intra-erythrocytic trophozoite, primary and secondary merogonic stages and a molecular analysis (partial 18S rDNA). Dactylosoma piperis n. sp. forms a well-supported clade with other Dactylosomatidae. This is the first molecular characterization of a species of Dactylosoma from a Brazilian anuran.

Abstract Background Bacille Calmette-Guerin (BCG) is currently the only available vaccine against tuberculosis (TB) and comprises a heterogeneous family of sub-strains with genotypic and phenotypic differences. The World Health Organization (WHO) affirms that the characterization of BCG sub-strains, both on genomic and proteomic levels, is crucial for a better comprehension of the vaccine. In addition, these studies can contribute in the development of a more efficient vaccine against TB. Here, we combine two-dimensional electrophoresis (2DE) and mass spectrometry to analyse the proteomic profile of culture filtrate proteins (CFPs) from M. bovis BCG Moreau, the Brazilian vaccine strain, comparing it to that of BCG Pasteur. CFPs are considered of great importance given their dominant immunogenicity and role in pathogenesis, being available for interaction with host cells since early infection. Results The 2DE proteomic map of M. bovis BCG Moreau CFPs in the pH range 3 - 8 allowed the identification of 158 spots corresponding to 101 different proteins, identified by MS/MS. Comparison to BCG Pasteur highlights the great similarity between these BCG strains. However, quantitative analysis shows a higher expression of immunogenic proteins such as Rv1860 (BCG1896, Apa), Rv1926c (BCG1965c, Mpb63) and Rv1886c (BCG1923c, Ag85B) in BCG Moreau when compared to BCG Pasteur, while some heat shock proteins, such as Rv0440 (BCG0479, GroEL2) and Rv0350 (BCG0389, DnaK), show the opposite pattern. Conclusions Here we report the detailed 2DE profile of CFPs from M. bovis BCG Moreau and its comparison to BCG Pasteur, identifying differences that may provide relevant information on vaccine efficacy. These findings contribute to the detailed characterization of the Brazilian vaccine strain against TB, revealing aspects that may lead to a better understanding of the factors leading to BCG's variable protective efficacy against TB.

Limonene, a monoterpene found in essential oils, has various activities, such as antifungal, antioxidant, neuroprotective, gastroprotective and vasorelaxant. However, the observation of limonene's biphasic effect in preclinical studies provides crucial information about its dose-dependent actions. Understanding this behavior is essential for optimizing therapeutic doses and anticipating possible side effects prior to clinical trials. The objective of this study is to provide a more detailed characterization and investigation of the mechanisms of action of limonene on the contractile tonus of isolated aorta.The experiments were carried out on aortic rings isolated from rats, subjected to isometric recording of contractions in their circular smooth muscle and exposed to different concentrations of limonene. It was found that limonene blocked the contraction induced by KCl (60 mM), but had a biphasic effect on the contraction induced by phenylephrine (0.1 μM). At lower concentrations, limonene was able to amplify the contraction induced by phenylephrine, while at higher concentrations, it inhibited it. The nitric oxide synthase blockers L-NAME and ruthenium red, a TRP ion channel blocker, did not significantly interfere with the biphasic character of limonene. However, indomethacin, a blocker of arachidonic acid derivatives, completely blocked the amplification of contraction induced by phenylephrine. In addition, limonene promoted relaxation in contractions induced by BAY-K 8644, a calcium channel agonist and by Ba 2+ . Limonene has complex effects on aortic tone, amplifying or inhibiting contractions, suggesting that the therapeutic window should be carefully studied to optimize clinical results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Leishmaniasis are zoonosis widely spread in Brazil, caused by the protozoan of the genus Leishmania, which includes several species. The disease manifests itself in the visceral or tegumentary form, and the main reservoir is the dogs. Manaus is the largest city in the Brazilian Amazon region, and despite the importance of the municipality, practically nothing is known about leishmaniosis in humans and animals. The objective of this study was to evaluate the occurrence and risk factors associated with the presence of Leishmania infantum in domiciliated dogs from Manaus. Molecular (polymerase chain reaction) and serological (immunofluorescent antibody test) methods were used as an indication of the circulation of the parasite. Blood samples for 154 domiciled dogs were obtained, and prevalence ratio and analysis of the variables were performed. Serum antibodies anti-Leishmania spp. were detected in 20.8% (95% CI: 14.4%-27.2%). Access to the street and zone of residence (P < 0.01) were associated with higher seropositivity. Molecular diagnosis for L. infantum detected positivity in 60 (39%) of the 154 (95% CI: 31.3%-46.7%) animals, and the variables street access, contact with dogs, and zone of residence were associated with higher frequencies of positivity (P < 0.05). Both serology and molecular diagnosis detected positive dogs in the municipality. This is the first description of the circulation of L. infantum infecting dogs in Manaus. As the municipality is classified as nonendemic, studies of isolation and characterization of the isolate must be done urgently., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Tools for assessing a country's capacity in the face of public health emergencies must be reviewed, as they were not predictive of the COVID-19 pandemic. Social cohesion and risk communication, which are related to trust in government and trust in others, may have influenced adherence to government measures and mortality rates due to COVID-19., Objective: To analyse the association between indicators of social cohesion and risk communication and COVID-19 outcomes in 213 countries., Results: Social cohesion and risk communication, in their dimensions (public trust in politicians, trust in others, social safety nets, and equal distribution of resources index), were associated with lower excess mortality due to COVID-19. The number of COVID-19-related disorder events and government transparency were associated with higher excess mortality due to COVID-19. The lower the percentage of unemployed people, the higher the excess mortality due to COVID-19. Most of the social cohesion and risk communication variables were associated with better vaccination indicators, except for social capital and engaged society, which had no statistically significant association. The greater the gender equality, the better the vaccination indicators, such as the number of people who received all doses., Conclusion: Public trust in politicians, trust in others, equal distribution of resources and government that cares about the most vulnerable, starting with the implementation of programs, such as cash transfers and combating food insecurity, were factors that reduced the excess mortality due to COVID-19. Countries, especially those with limited resources and marked by social, economic, and health inequalities, must invest in strengthening social cohesion and risk communication, which are robust strategies to better cope with future pandemics., (© 2024. The Author(s).)

We demonstrate a broadband acousto-optic notch filter based on a tubular-lattice hollow-core fiber for the first time to our knowledge. The guided optical modes are modulated by acoustically induced dynamic long-period gratings along the fiber. The device is fabricated employing a short interaction length (7.7 cm) and low drive voltages (10 V). Modulated spectral bands with 20 nm half-width and maximum depths greater than 60% are achieved. The resonant notch wavelength is tuned from 743 to 1355 nm (612 nm span) by changing the frequency of the electrical signal. The results indicate a broader tuning range compared to previous studies using standard and hollow-core fibers. It further reveals unique properties for reconfigurable spectral filters and fiber lasers, pointing to the fast switching and highly efficient modulation of all-fiber photonic devices.

Background: National governance may have influenced the response of institutions to the Covid-19 pandemic, being a key factor in preparing for the next pandemics. The objective was to analyze the association between excess mortality due to COVID-19 (daily and cumulative per 100 thousand people) and national governance indicators in 213 countries., Method: Multiple linear regression models using secondary data from large international datasets that are in the public domain were performed. Governance indicators corresponded to six dimensions: (i) Voice and Accountability; (ii) Political Stability and Absence of Violence/Terrorism; (iii) Government Effectiveness; (iv) Regulatory Quality; (v) Rule of Law and (vi) Control of Corruption. The statistical analysis consisted of adjusting a multiple linear regression model. Excess mortality due to COVID-19 was adjusted for potential confounding factors (demographic, environmental, health, economic, and ethnic variables)., Results: The indicators Control of Corruption, Government Effectiveness, Regulatory Quality and Rule of Law had a significant inverse association (p < 0.0001) with the estimated excess mortality in 2020, 2021 and 2022. Furthermore, the governance indicators had a direct significant association (p < 0.0001) with the vaccination variables (People&#95;fully&#95;vaccinated; Delivered population; The total number of vaccination doses administered per 100 people at the country level), except for the variables Vaccination policies and Administration of first dose, which were inversely associated. In countries with better governance, COVID-19 vaccination was initiated earlier., Conclusion: Better national governance indicators were associated with lower excess mortality due to COVID-19 and faster administration of the first dose of the COVID-19 vaccine., (© 2023. The Author(s).)

Background Aims: Advanced therapy medicinal products (ATMPs) are a class of biological products for human use that are based on gene, tissues or cells. ATMPs have peculiar characteristics when compared with traditional medicines. In this regard, long-term safety and efficacy follow-up systems of individuals treated with ATMPs have become necessary and may present unique challenges, because unlike conventional drugs and biologics, these products can exert their effects for years after administration. This work seeks to assess the requirements foreseen in the regulatory frameworks for the post-marketing authorization safety and efficacy surveillance for ATMPs in Brazil, European Union (EU), Japan and United States, which are some of the members of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use., Methods: We reviewed the scientific literature and official documents of regulatory agencies (RAs) in Brazil, the EU, Japan and the United States., Results and Conclusions: RAs in the EU, US and Japan have developed regulatory guidelines for the post-marketing surveillance of ATMPs. These guidelines aim at implementing surveillance plans for monitoring adverse events, including late ones, after marketing authorization. All the ATMPs authorized by the RAs studied, submitted some type of post-marketing requirement to supplement safety and efficacy data, according to the regulations and terminology used by those jurisdictions., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Background: ( E , E )-farnesol is a sesquiterpene alcohol derived from plants and animals that exhibits pharmacological properties in the cardiovascular system. However, its effects on human umbilical vessels remain unknown., Purpose: Thus, this study aims to characterize the vasodilatory effect of ( E , E )-farnesol in human umbilical arteries (HUA)., Study Design: The tissue is obtained from pregnant women over 18 years of age, normotensive, and without prepartum complications. After collected, the tissue was segmented and dissected to remove Wharton's jelly and obtain the umbilical arteries segments., Methods: HUA segments were isolated and sectioned into rings that were subjected to isometric tension recordings in an organ bath., Results: ( E , E )-farnesol (1 μmol/L to 1 mmol/L) promoted vasodilatory effect in HUA preparations, affecting basal tone, and inhibiting the electromechanical coupling induced by KCl 60 mmol/L with greater potency (EC 50 225.3 μmol/L) than the pharmacomechanical coupling induced by 5-HT 10 μmol/L (EC 50 363.5 μmol/L). In the absence of extracellular calcium, pharmacomechanical coupling was also abolished, and contractions induced by CaCl 2 or BaCl 2 were attenuated by ( E , E )-farnesol indicating a possible direct inhibition of L-type VOCC as a mechanism of the vasodilatory effect. The vasodilator efficacy of ( E , E )-farnesol on reduction of vasocontraction induced by the presence of tetraethylammonium (1 or 10 mmol/L), 4-aminopyridine (1 mmol/L) and glibenclamide (10 μmol/L) suggesting a possible influence of different potassium channels (BK Ca , K V and K ATP )., Conclusion: These results suggest that ( E , E )-farnesol may be a promising pharmacological candidate for obstetric hypertensive disorders., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Treatment guidance for children and older adult patients affected by cutaneous leishmaniasis (CL) is unclear due to limited representation of these groups in clinical trials., Methods: We conducted a collaborative retrospective study to describe the effectiveness and safety of antileishmanial treatments in children ≤ 10 and adults ≥ 60 years of age, treated between 2014 and 2018 in ten CL referral centers in Latin America., Results: 2,037 clinical records were assessed for eligibility. Of them, the main reason for non-inclusion was lack of data on treatment follow-up and therapeutic response (182/242, 75% of children and 179/468, 38% of adults). Data on 1,325 eligible CL patients (736 children and 589 older adults) were analyzed. In both age groups, disease presentation was mild, with a median number of lesions of one (IQR: 1-2) and median lesion diameter of less than 3 cm. Less than 50% of the patients had data for two or more follow-up visits post-treatment (being only 28% in pediatric patients). Systemic antimonials were the most common monotherapy regimen in both age groups (590/736, 80.2% of children and 308/589, 52.3% of older adults) with overall cure rates of 54.6% (95% CI: 50.5-58.6%) and 68.2% (95% CI: 62.6-73.4%), respectively. Other treatments used include miltefosine, amphotericin B, intralesional antimonials, and pentamidine. Adverse reactions related to the main treatment were experienced in 11.9% (86/722) of children versus 38.4% (206/537) of older adults. Most adverse reactions were of mild intensity., Conclusion: Our findings support the need for greater availability and use of alternatives to systemic antimonials, particularly local therapies, and development of strategies to improve patient follow-up across the region, with special attention to pediatric populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Castro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background Aims: Advanced therapy medicinal products (ATMPs) are a class of biological products for human use that are based on genes, cells and tissues. The first ATMP received marketing authorization in Europe in 2009, whereas Brazil granted the first authorization in 2020. The objective of this study was to compare the regulatory models adopted by Brazil, the USA, Japan and the European Union, which comprise the member countries of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, with regard to the marketing authorization of ATMPs., Methods: The authors performed a review of the scientific literature and official documents of the regulatory agencies in the aforementioned countries., Results: The legislation and regulatory guidelines adopted by the regulatory agencies exhibit similarities and differences. It was not possible to assess whether these differences can be translated into divergent final recommendations by regulatory authorities upon a request for marketing authorization., Conclusions: In the future, it will be appropriate to start a progressive process of harmonization between these agencies in terms of terminology, legal recommendations and characterization requirements. This is particularly important for emerging countries such as Brazil. In this sense, some measures can be taken to achieve alignment between regulators., (Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

The phylum Arthropoda comprises approximately 85% of all described animal species. The class Arachnida includes some invertebrates of great importance as they are either involved in the transmission of diseases or poses a risk of human envenomation. Spiders belonging to the genus Phoneutria sp., are the arachnids exhibiting medical importance. These animals were quarantined and maintained in captivity at the Biotério de Artrópodes of the Instituto Butantan, São Paulo, Brazil, for the production of the anti-arachnid serum. A total 509 feces samples from different Phoneutria nigriventer were analyzed, and 131 (25.73%) samples were found to be positive for flagellates and ciliates. All positive samples were subjected to DNA extraction and amplification of 18S gene. A total of 16 sequences were obtained and analyzed using BLAST. Sequences were identified as Colpoda steiini, one as Colpoda aspera, one to Colpoda sp., and one as "ciliated". Four identified as Parabodo caudatus, two as Urostipulosphaera sp., one as Helkesimastix sp. , and one as a Euglena-like. The presence of clinical signs was observed in 16 spiders. The intestinal protozoa that affect armed spiders were identified for the first time as an initial step for understanding the parasitic diseases in these organisms., Competing Interests: None., (© 2021 The Authors.)

Trypanosoma vivax Ziemann is a parasite that affects both wild and domestic ungulates and is transmitted mechanically via tabanids and other blood-sucking insects in the Americas. A total of 621 blood samples from water buffaloes (Bubalus bubalis (Linnaeus) (Artiodactyla: Bovidae), and 184 ectoparasite samples (Amblyomma cajennense (Fabricius) sensu stricto and Rhipicephalus (Boophilus) microplus (Canestrini) (Acari: Ixodidae), and Haematopinus tuberculatus (Burmeister) (Phthiraptera: Haematopinidae)) were obtained from 60 farms in the State of Pará, Brazilian Amazon. Twelve buffalo blood samples (1.89%) and 11 ectoparasites (6%) were positive for T. vivax based on the cathepsin L-like gene. All sequences were 99% similar to T. vivax from northeastern Brazil (EU753788) in amplified PCR assays on each of the hosts tested., (© The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The importance of age estimation in the forensic field is inherent to the process of establishing the biological profile of children, sub-adults and adults. The established profile might be useful for the identification of deceased victims or living individuals when it comes to age of legal interest. In parallel, age estimation is also investigated for clinical purposes, especially for the diagnosis of dental and bone maturation. Several studies were developed to provide accurate age estimation methods based on skeletal and dental development. This study aimed to apply and compare Cameriere's and Willems' methods for dental age estimation in a Brazilian sample. Two examiners performed image analysis and method application in 180 panoramic radiographs of Brazilian children aged 6-14 years old. The ages estimated with both methods revealed a good correlation with the chronological ages of Brazilian boys and girls. Cameriere's method showed a slight underestimation of 0.05 years for girls and 0.03 for boys. Willems' method, on the other hand, showed an overestimation of -0.47 years for girls and -0.39 for boys. Better age estimates were obtained combining the outcomes of both methods. In practice, Cameriere's and Willems' methods reached reliable outcomes and could be applied for dental age estimation purposes.

Caffeic acid is a phenolic compound widely found in commonly consumed foods such as pears, apples and coffee, and is pharmacologically known for its antioxidant, anti-inflammatory and anti-asthmatic properties. However, its relaxant activity in the aorta, uterus and ileum smooth muscle has not been investigated. This study aimed to comparatively evaluate the effect of caffeic acid on smooth muscle from different organs (aorta, uterus and ileum), and the contractions of this different organ were induced by different agonists. The organ bath technique was used, where the organs were placed in different cuvettes with 10 mL of Tyrode solution for 1 h to stabilize, then, myometrial, intestinal strip and aortic ring contractions were evoked using different contractile agonists (KCl 60 mM, PHE 0.1 μM, OT 10-2 IU/mL, CCh 10 -6  M and BaCl 2 0.1-30 mM); increasing concentrations of caffeic acid (0.03-7 mM) were administered in the experimental preparations. In the presence of KCl (60 mM), caffeic acid caused relaxations with the following EC 50 values: 2.7 ± 0.26 mM/mL (aorta), 5.7 ± 0.71 mM/mL (uterus) and 2.1 ± 0.39 mM/mL (ileum). When in the presence of different agonists, PHE (0.1 μM) for the aorta, OT (10 -2 IU/mL) for the uterus and CCh (10 -6  M) for the ileum, caffeic acid caused relaxations with EC 50 values of: 2.7 ± 0.31 mM/mL; 2.2 ± 0.34 mM/mL and 2.0 ± 0.28 mM/mL, respectively. The inhibitory effect of caffeic acid on serotonergic (aorta and uterus) and muscarinic receptors (uterus and ileum), as well as its possible involvement with L-type Ca 2+ channels, was also observed. This study reports the pharmacological characterization of caffeic acid on smooth muscle from different organs, for which caffeic acid was more potent in the ileum. A diverse understanding of its performance as a possible therapeutic product is attributed to its relaxant effect., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Resistance to antimicrobials is a challenging issue that complicates the treatment of infections caused by bacteria and fungi, thus requiring new therapeutic options. Oncocalyxone A, a benzoquinone obtained from Auxemma oncocalyx (Allem) Taub has several biological effects; however, there is no data on its antimicrobial action. In this study, its antimicrobial and antibiofilm activities were evaluated against bacteria and fungi of clinical interest. Strains of Gram-positive and Gram-negative bacteria, and filamentous fungi and yeasts were selected to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of oncocalyxone A. The antibacterial effect of oncocalyxone A was studied using survival curves, atomic force microscopy (AFM), and the involvement of oxidative stress. We examined the inhibitory action of the molecule on biofilm formation and its hemolytic activity against human erythrocytes. Our results showed that among the strains tested, Staphylococcus epidermidis was highly sensitive to the action of oncocalyxone A, with an MIC of 9.43 μg/mL. In most bacterial strains analyzed, a bacteriostatic effect was observed, though the molecule showed no antifungal activity. Antibiofilm activity was observed against the methicillin-resistant S. aureus bacteria. Additionally, results from atomic force microscopy imaging showed that oncocalyxone A significantly altered bacterial morphology. Further, oncocalyxone A showed no hemolytic activity at concentrations ≥151 μg/mL. Together, our results demonstrate the antibacterial and antibiofilm potential of oncocalyxone A, indicating its therapeutic potential against bacterial resistance., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Photodynamic therapy (PDT) is a process that uses a light source (e.g. laser), oxygen molecules and a photosensitizing agent. PDT aims to act against pathogens, including those resistant to antimicrobials. The association of PDT with natural drugs, such as Propolis, has not been widely studied. Methods: Therefore, this study aimed to evaluate the antimicrobial effect of PDT in vitro by using Propolis as a photosensitizing agent. For this purpose, the dry Propolis extract was used as a photosensitizer and a low-power laser (Photon Laser III model) was irradiated onto the microwells for 90 seconds. Gram-positive and Gram-negative bacterial strains were used in the tests at a concentration of 5 × 10 5 CFU/mL. Initially, the antibacterial activity of the photosensitizers without laser action was determined by using a serial microdilution method before the experiment with a laser. After the incubation of the plates in a bacteriological oven, resazurin (0.1%) was added and the minimum inhibitory concentration (MIC) was determined. Alterations in the morphology of the bacteria were analysed by using atomic force microscopy (AFM). Results: Bacteria were sensitive to Propolis with MICs ranging from 13.75 to 0.85 mg/mL, but no susceptibility was observed for methylene blue without laser application. A change was observed for MIC values of Propolis against Staphylococcus aureus after irradiation, which decreased from 1.71 mg/mL to 0.85 mg/mL. However, this behaviour was not observed in Escherichia coli , the only gram-negative strain used. In addition, AFM images revealed alterations in the size of one of the bacteria tested. Conclusion: The Propolis is more active against gram-positive bacteria and PDT improved its activity against one of the strains tested., (Copyright © 2020 J Lasers Med Sci.)

Background: Brazilian patients have legal right to access unlicensed medicines undergoing clinical research, if there is evidence of efficacy and safety. This study investigated the occurrence of serious adverse events related to very high-cost medicines from clinical studies, expanded access and compassionate use programs, obtained by patients though health litigation., Methods: A descriptive study using secondary data investigated unlicensed medicines obtained through lawsuits from 2010 to 2017, costing more than 1 million Brazilian reais (BRL), adjusted by the Brazilian Consumer Index to July 2017. Data sources were the Brazilian Health Surveillance Agency Registry (DATAVISA) and Adverse Events in Clinical Studies (NotivisaEC) Databases. Medicines were categorized by the Anatomical Therapeutic Chemical classification to level 03 and events by the WHO Adverse Drug Reaction Terminology. The study received ethical approval by the University of Brasilia Institutional Research Board., Results: In the period, 812 drugs were obtained through litigation, and of these, 78 exceeded cost of 1 million BRL; 44 of them presented reports of 1,248 serious adverse events. Total Brazilian Government expenditure with these drugs was 3.2 billion BRL. Class L04A (n=7) showed greater expenditures (over 1.8 billion BRL). One hundred ninety-six deaths occurred and L01X was the most involved category (49.5%). Most other serious events (n=419) and sequelae (n=10) were related to L01X., Conclusion: Very high-cost drugs paid for by the government and obtained through health litigation presented deaths and serious adverse events in expanded access and compassionate use programs in Brazil., (Copyright © 2020 Silva, Lima, Novaes and Osorio-de-Castro.)

Objectives : Cutaneous leishmaniasis is a neglected disease, associated with high morbidity, which is partially due to the toxicity of available therapies. The pentavalent antimonial derivatives intralesional infiltration has proven to be as effective as the intravenous drug-based therapy, however, there is a lack of robust safety data. Methods : Phase II, uncontrolled, unicenter clinical trial to assess the safety profile of a standardized meglumine antimionate intralesional therapy, based on weekly infiltrations. Results : Fifty-three patients were studied, predominantly men (60%) and young adults (43.7 ± 17.1 years). Overall, 86.9% of the patients had at least one clinical adverse event. Local events were the most frequent (83%), followed by systemic ones (47.3%). Fourteen participants (26%) presented biochemical abnormalities. In all cases, laboratorial alterations were classified as mild and treatment discontinuation was not required. Differently, the two hypersensitivity (3.8%) reactions observed led to permanent treatment interruption. QTc interval prolongation was recorded in 14 patients (25.5%). The following risk associations to adverse events were identified in the multiple analysis: hypertension with systemic clinical events and smoking with QT interval prolongation. Expert commentary : In general, MA-IL was well tolerated and although associated with local and systemic adverse events, there was a low risk of high intensity or severe complications.

Background: Leishmania infantum, the etiological agent of visceral leishmaniasis, is a neglected zoonosis that requires validation and standardization of satisfactory diagnostic methodologies. Thus, the aim of the present study was to evaluate the effectiveness of cathepsin L-like protease as a target for making molecular diagnoses and as a phylogenetic marker enabling to understand the intraspecies variations and evolutionary history of L. infantum in Brazil., Methods: We used 44 isolates of L. infantum. The cathepsin L-like gene fragments were amplified, sequenced, manually aligned and analyzed using inference methods. The sequences generated were used to search and design oligonucleotide primers to be used in reactions specific to the target parasite., Results: The cathepsin L-like gene did not show any intraspecies variability among the isolates analyzed. The pair of primers proposed amplified the target deoxyribonucleic acid (DNA) of L. infantum isolates and were effective for DNA amplification at concentrations of as low as 10 - 11  ng/μl. The proposed marker did not present cross-reactions with other hemoparasites. When used for making the diagnosis in a panel of clinical samples from dogs, a positivity rate of 49.03% (102/208) was obtained, versus 14.42% (30/208) for a ribosomal internal transcribed spacer (ITS) marker. In samples from sandflies, the rate was 6.25% and from humans, 14.28%., Conclusions: The results described in this work allow us to infer that CatLeish-PCR is a sensitive and specific marker for use in diagnostic trials of L. infantum and in clinical and epidemiological surveys.

Objective: Evaluate the pattern of intraocular pressure (IOP) variations through the pneumatic tonometer, between two specific surgical techniques, and the possible variables that may influence the behavior of this pressure., Methods: Retrospective cross-sectional study carried out through the review of electronic medical records of a private ophthalmological reference hospital in the city of Goiânia, Goiás, Brazil, from 2012 to 2016, comprising of a sample of 550 eyes. The analyzed variables were, age, gender, IOP, axis, pachymetry, anterior chamber depth, and axial length., Results: In the end, the study consisted of 231 eyes, represented by 179 patients. Of these, 182 eyes were operated on by isolated cataract surgery, with a mean age of 72.0±9.5 years. The combined surgery represented a total of 49 eyes, 34 patients with a mean age of 71.9±8.14 years. There was statistical significance ( P <0.05) in correlating the pre- and postoperative IOP values in the 24-hour, 7-, 15-day, and 12-month postoperative periods., Conclusion: A standard of variation of IOP was found through the pneumatic tonometer in both surgical techniques, but a more significant reduction was observed in combined surgery than in isolated cataract surgery, and further studies with a greater epidemiological impact are required for confirmation of this conclusion., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: Participants' rights and safety must be guaranteed not only while a clinical trial is being conducted but also when a clinical trial finishes. The criteria for post-trial access to experimental drugs, however, are unclear in various countries. The objectives of this study were (i) to ascertain if there were regulations or guidelines related to patients' access to drugs after the end of clinical trials in the countries selected in the study and (ii) to analyze trends in post-trial access in countries classified by their level of economic development., Methods: This study is a retrospective review. The data are from the records of clinical trials from 2014 registered in the World Health Organization's International Clinical Trials Registry Platform (ICTRP) database., Results: Among the countries selected, provision of drugs post-trial is mandatory only in Argentina, Brazil, Chile, Finland, and Peru. The plans for post-trial access tend to be more present in low- and middle-income and upper middle-income countries, in comparison with high-income countries. Studies involving vulnerable populations are 2.53 times more likely to have plans for post-trial access than studies which do not., Conclusions: The guaranteeing of post-trial access remains mandatory in few countries. Considering that individuals seen as vulnerable have been included in clinical trials without plans for post-trial access, stakeholders must discuss the need to develop regulations mandating the guaranteeing of post-trial access in specified situations.

Cancer incidence has increased significantly in low- and middle-income countries. The priorities of international health research are not always aligned with the global burden of cancer. This study aims to analyze global tendencies in clinical trials in oncology and discuss research priorities and resource allocation in the investigation of new drugs for cancers that significantly affect the least developed countries. This was a retrospective and analytical study that included data collected from the World Health Organization's International Clinical Trials Registry Platform (ICTRP) in 2014. According to our results, there was a tendency for clinical trials involving breast and lung cancer to be conducted in countries with a lower level of economic development. On the other hand, cervical, stomach, and liver cancer, despite the significant burden that these place on middle- and low-income countries, were studied little among the countries selected. In conclusion, the organizations that most fund research to develop new drugs for cancer treatment continue to show little interest in prioritizing resources to fund research for certain types of cancer such as those of the cervix, stomach, and liver, which have a significant impact in low- and middle-income countries.

Objective: To evaluate the intraocular pressure variation before and after phacoemulsification through pneumatic tonometry in addition to correlating it with the age, gender, and preoperative intraocular pressure of the patients evaluated., Methods: This is a cross-sectional observational study. Inclusion criteria were older than 18 years, deep anterior chamber visualized by the slit lamp and estimation of open angle using the Van Herick technique, intraocular pressure less than 21 mmHg, without surgical complications, and without any ocular disease. The intraocular pressure was measured by the pneumatic tonometer. The intraocular pressure assessment was performed at the last consultation before phacoemulsification surgery and 30 days after., Results: A sample of 182 eyes was used. The mean age was 68.41 ± 10.84 years. Of the patient, 65% were females and 35% were males. The mean intraocular pressure in the preoperative period was 16.0 mmHg (±3.3 mmHg) and the mean intraocular pressure in the postoperative period was 13.44 mmHg (±3.31 mmHg). There was no correlation between intraocular pressure variations in both eyes (age-matched open angle) and age. There was a statistically significant correlation between the preoperative intraocular pressure value and the intraocular pressure changes in the postoperative period. In the comparison of the intraocular pressure variation between the genders, the female gender presented a statistically significant negative variation., Conclusion: We conclude that the cataract surgery is related to the reduction of intraocular pressure in the postoperative period and this reduction is more influenced by its preoperative value. Other studies of high epidemiological impact are needed, which may corroborate that the cataract surgery could directly influence intraocular pressure variation.

Stereotaxy is based on the precise image-guided spatial localization of targets within the human brain. Even with the recent advances in MRI technology, histological examination renders different (and complementary) information of the nervous tissue. Although several maps have been selected as a basis for correlating imaging results with the anatomical locations of sub-cortical structures, technical limitations interfere in a point-to-point correlation between imaging and anatomy due to the lack of precise correction for post-mortem tissue deformations caused by tissue fixation and processing. We present an alternative method to parcellate human brain cytoarchitectural regions, minimizing deformations caused by post-mortem and tissue-processing artifacts and enhancing segmentation by means of modified high thickness histological techniques and registration with MRI of the same specimen and into MNI space (ICBM152). A three-dimensional (3D) histological atlas of the human thalamus, basal ganglia, and basal forebrain cholinergic system is displayed. Structure's segmentations were performed in high-resolution dark-field and light-field microscopy. Bidimensional non-linear registration of the histological slices was followed by 3D registration with in situ MRI of the same subject. Manual and automated registration procedures were adopted and compared. To evaluate the quality of the registration procedures, Dice similarity coefficient and normalized weighted spectral distance were calculated and the results indicate good overlap between registered volumes and a small shape difference between them in both manual and automated registration methods. High thickness high-resolution histological slices in combination with registration to in situ MRI of the same subject provide an effective alternative method to study nuclear boundaries in the human brain, enhancing segmentation and demanding less resources and time for tissue processing than traditional methods.

Background: Although policies and guidelines make use of the concept of vulnerability, few define it. The European Union's directive for clinical trials does not include explanations for or the reasoning behind the designation of certain groups as vulnerable. Emerging economies from lower middle-income countries have, in recent years, had the largest average annual growth rate, as well as increase, in number of clinical trials registered in the US government's database. Nevertheless, careful supervision of research activities has to be ensured. Objective: To describe and analyze the features of the clinical trials involving vulnerable populations in various countries classified by development status and geographic region. Methods: Retrospective study that involved analysis of data obtained from the International Clinical Trials Registry Platform (ICTRP) database between 01/2014 and 12/2014 from countries with (i) highest trial densities during 2005 to 2012, (ii) highest average growth rate in clinical trials, and (iii) greatest trial capabilities. Results: Statistical analysis of this study showed that patients incapable of giving consent personally are 11.4 times more likely to be vulnerable patients than patients who are capable, and that patients in upper-middle-income countries are 1.7 times more likely to be vulnerable patients than patients from high-income countries when participating in global clinical trials. Malaysia (21%), Egypt (20%), Turkey (19%), Israel (18%), and Brazil (17%) had the highest percentages of vulnerable populations involving children. Conclusions: Although the inability to provide consent personally was a factor associated with vulnerability, arbitrary criteria may have been considered when classifying the populations of clinical trials as vulnerable. The EU Clinical Trials Register should provide guidance regarding exactly what aspects or factors should be taken into account to frame given populations as vulnerable, because vulnerability is not applicable to all risk situations.

Introduction: Although international health research involves some benefits for the host countries, such as access to innovative treatments, the research itself may not be aligned with their communities' actual health needs. Objective: To map the global landscape of clinical trials run in Latin American and Caribbean countries and discuss the addressing of local health needs in the agenda of international clinical trials. Methods: The present study is a cross-sectional overview and used data referent to studies registered between 01/01/2014 and 12/31/2014 in the World Health Organization's (WHO) International Clinical Trials Registry Platform (ICTRP). Results: Non-communicable diseases such as diabetes, cancer, and asthma-studies which were financed mainly by industries-were the conditions investigated most in the region of Latin America and the Caribbean. The neglected diseases, on the other hand, such as Chagas disease, and dengue, made up 1% of the total number of studies. Hospitals and nonprofit nongovernmental organizations prioritize resources for investigating new drugs for neglected diseases, such as Chagas disease and dengue. Conclusion: The international multicenter clinical trials for investigating new drugs are aligned with the health needs of the region of Latin America and the Caribbean, when one considers the burden resulting from the non-communicable diseases in this region. However, the transmissible diseases, such as tuberculosis and AIDS, and the neglected diseases, such as Chagas disease and dengue, which have an important impact on public health in this region, continue to arouse little interest among the institutions which finance the clinical trials.

Glutamate decarboxylase or glutamic acid decarboxylase (GAD) is a protein associated with autoimmune diseases, including type-1 diabetes. This disease is primarily associated with the occurrence of a specific isoform: GAD65. Conversely, some specific peptides of this protein may block autoimmunity in diabetes. In this respect, understanding the relationship between GAD and the development of diabetes is important, and it is necessary to understand the role of each GAD peptide to design effective autoimmune diabetes treatments. The purpose of the present study was to analyze the effects of treatment with GAD-derived peptides p217 and p290 on INS receptors in the salivary epithelium of nonobese diabetic (NOD) animals. Three groups of 7 mice each were studied: I, BALB/c mice (control); II, NOD mice; and III, NOD mice treated with peptides p290 and p217. Groups I and II only received buffered saline solution. Glucose levels were measured daily during the 21 days of the experiment. After the study, the animals were euthanized and the parotid and submandibular glands were removed for the analysis of INS-R by fluorescence microscopy. Therapy with two peptides together was associated with reduced glucose levels in NOD mice and intense INS-R expression in both salivary organs. Our approach of combining GAD p217 and p290 peptides contributed to hormonal balance and promoted the repair of INS-R.

Objective: We propose the use of a formal approach to support content validation of a standard operating procedure (SOP) for a therapeutic intervention. Such an approach provides a useful tool to identify ambiguities, omissions and inconsistencies, and improves the applicability and efficacy of documents in the health settings., Materials and Methods: We apply and evaluate a methodology originally proposed for the verification of software specification documents to a specific SOP. The verification methodology uses the graph formalism to model the document. Semi-automatic analysis identifies possible problems in the model and in the original document. The verification is an iterative process that identifies possible faults in the original text that should be revised by its authors and/or specialists., Results: The proposed method was able to identify 23 possible issues in the original document (ambiguities, omissions, redundant information, and inaccuracies, among others). The formal verification process aided the specialists to consider a wider range of usage scenarios and to identify which instructions form the kernel of the proposed SOP and which ones represent additional or required knowledge that are mandatory for the correct application of the medical document., Conclusion: By using the proposed verification process, a simpler and yet more complete SOP could be produced. As consequence, during the validation process the experts received a more mature document and could focus on the technical aspects of the procedure itself., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The authors report the case of a 55-year-old female, hypertensive, smoker patient presenting with dysphonia, dysphagia and persistent dry cough. Laryngoscopy diagnosed left vocal cord paralysis. Computed tomography demonstrated saccular aneurysm of the inferior wall of the aortic arch, stretching the left recurrent laryngeal nerve, a finding compatible with Ortner's syndrome.

Natural products produced by microorganisms have been utilized as sources of new drugs possessing a wide range of agrochemical and pharmacological activities. During our research on Actinomycetes from Brazilian mangroves, the ethyl acetate extract of Streptomyces sp. AMC 23 isolated from the red mangrove (Rhizophora mangle) rhizosphere produced a highly active compound against the microalga Chlorella vulgaris, often used to assess the phytotoxic activity. As a result, the bioassay-guided fractionation led to the isolation of the mixture of the known compounds bafilomycin B1 and bafilomycin B2. The chemical structures of bafilomycin B1 and bafilomycin B2 were established based on their spectroscopic data by infrared (IR), mass spectrometry (MS), (1)H nuclear magnetic resonance (NMR), gradient-enhanced heteronuclear multiple quantum coherence (gHMQC), and gradient-enhanced heteronuclear multiple-bond connectivity (gHMBC) as well as comparison with reference data from the literature. Moreover, it was also possible to identify other bafilomycins using non-chromatographic-dependent techniques (Tandem mass spectrometry). Additionally, this is the first report on the phytotoxic activity of bafilomycin B1.

Objectives: The incretin-based therapy might be effective in patients possessing certain levels of preserved pancreatic beta-cells. However, doubts still exist regarding the efficacy of this atment in the recovery of tissues damaged by type 1 diabetes. Thus, the objective of this study was to evaluate the treatment with MK0431 in salivary glands of spontaneously diabetic mice, focusing mainly on the possible therapeutic and hypoglycaemic effects of this dipeptidyl peptidase IV inhibitor in the recovery of these salivary tissues., Methods and Results: Twenty mice were divided into two groups of 10 animals each: group I (NOD diabetic/untreated) and group II (NOD diabetic MK0431/treated). The group II was treated during 4 weeks with MK0431 mixed in the food. The group I was maintained in the same way without receiving, however, any treatment. Glucose levels were monitored during treatment and salivary glands samples were collected at the end of treatment for the histological examination under both transmitted and polarized light microscopy. High glucose levels were observed in untreated animals, while in animals with treatment, reduction of these levels was observed. Tissue restructuring was also observed in animals submitted to therapy with MK0431, mainly in relation to the attempt to extracellular matrix reorganization., Conclusions: According to results, the treatment with this dipeptidyl peptidase IV inhibitor contributed to the general homeostasis of the organism and to the reestablishment of both epithelial and stromal compartments which were damaged by the hyperglycaemic condition, demonstrating that the incretin-based therapy may be an important complementary treatment for the type 1 diabetic condition., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Cutaneous leishmaniasis (CL) may manifest as single or multiple skin lesions, causing significant aesthetic impact and affecting the patient's quality of life (QoL). The objective of this study was to assess the impact of CL on the QoL., Methods: The QoL of 20 patients with CL was assessed by the Dermatology Life Quality Index (DLQI)., Results: For 70% of patients CL had a moderate/large impact on their QoL, with 'Work and School' being the most affected domain. This is the first study to use the DLQI to assess the impact of CL., Conclusion: CL has a moderate to large negative effect on QoL.

The objective of this study was to evaluate the salivary glands in diabetic mice, analyzing alterations in the secretory epithelium and interactions with the stromal compartment acquired during a prolonged period of treatment with Bauhinia forficata extract. Female mice were divided into two groups: Nonobese diabetic (NOD) mice treated with Bauhinia forficata (I), and NOD mice not treated with the hypoglycemic agent (II). After treatment, the salivary glands were collected for analysis by transmitted and polarized light microscopy, complemented by three-dimensional analysis of these tissues. The results showed weight loss in animals of group II and weight recovery in treated animals. Glucose levels were elevated in group II, but declined in group I. In the two groups, the salivary glands were characterized by involution of the secretory epithelium, presence of an inflammatory infiltrate and an increase of extracellular fibrillar components. It can be concluded that treatment with Bauhinia forficata reduced glucose levels and contributed to weight recovery in treated animals. However, the observation of tissue destructuring and compromised epithelial-stromal interactions, with consequent impairment of glandular function, demonstrates that Bauhinia forficata exerts an effect on the recovery of body metabolism but this improvement does not influence in the tissue recovery.

This is a clinical trial which aims to evaluate the efficiency of massage in the reduction of occupational low back pain, and its influence on the performance of work and life activities for the nursing team. The sample consisted of 18 employees who received seven to eight sessions after their work period. From the Numerical Pain Rating Scale, significant improvements were found between the 3rd and 1st evaluations (p=0.000) and between the 3rd and 2nd (p=0.004), using the Wilcoxon test. Regarding the Oswestry Disability Index, the paired t test showed a statistical difference (p=0.02) between the baseline, with a mean of 21.33% and the second evaluation (18.78%), which was also seen between the second and third evaluation (16.67%). The score for the Handling and Transfer Risk Evaluation Scale was 18 points (medium risk). It is concluded that massage was effective in reducing occupational low back pain, and provided improvement in activities of work and life. Clinical Trials Identifier: NCT01315197.

Background: The aim of this study is to compare the effect of physical exercise program on the endothelial function of patients with metabolic syndrome and type 2 diabetes mellitus., Methods: Patients were randomized for high intensity aerobic training (HI: 80% maximum heart rate, n=10), low intensity aerobic training (LI: 55% of maximum heart rate, n=10) and control (n=11). Before and after 6 weeks of training, subjects performed the maximal exercise test and a study of the endothelial function, through a high resolution ultrasound of the brachial artery, which was assessed after reactive hyperemia (endothelium dependent vasodilation) and nitrate administration (endothelium independent vasodilation)., Results: A total of 31 patients with metabolic syndrome and type 2 diabetes mellitus were studied, with mean age of 58±6 years, The percentage diameter difference of the vessel after hyperemia was significantly higher for the high intensity group (HI before 2.52±2.85% and after 31.81±12.21%; LI before 3.23±3.52% and after 20.61±7.76%; controls before 3.56±2.33% and after 2.43±2.14%; p<0.05)., Conclusions: High intensity aerobic training improved the functional capability and endothelium dependent vasodilator response, but it does not improve the endothelium independent vasodilation in patients with metabolic syndrome and type 2 diabetes mellitus., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

A type of ZrO(2).nH(2)O was synthesized and its Cr(VI) removal potential was investigated in this study. The kinetic study, adsorption isotherm, pH effect, thermodynamic study and desorption were examined in batch experiments. The kinetic process was described by a pseudo-second-order rate model very well. The Cr(VI) adsorption tended to increase with a decrease of pH. The adsorption data fitted well to the Langmuir model. The adsorption capacity increased from 61 to 66 mg g(-1) when the temperature was increased from 298 to 338 K. The positive values of both Delta H degrees and DeltaS degrees suggest an endothermic reaction and increase in randomness at the solid-liquid interface during the adsorption. Delta G degrees values obtained were negative indicating a spontaneous adsorption process. The effective desorption of Cr(VI) on ZrO(2).nH(2)O could be achieved using distilled water at pH 12.

The histopathological counterpart of white matter hyperintensities is a matter of debate. Methodological and ethical limitations have prevented this question to be elucidated. We want to introduce a protocol applying state-of-the-art methods in order to solve fundamental questions regarding the neuroimaging-neuropathological uncertainties comprising the most common white matter hyperintensities [WMHs] seen in aging. By this protocol, the correlation between signal features in in situ, post mortem MRI-derived methods, including DTI and MTR and quantitative and qualitative histopathology can be investigated. We are mainly interested in determining the precise neuroanatomical substrate of incipient WMHs. A major issue in this protocol is the exact co-registration of small lesion in a tridimensional coordinate system that compensates tissue deformations after histological processing. The protocol is based on four principles: post mortem MRI in situ performed in a short post mortem interval, minimal brain deformation during processing, thick serial histological sections and computer-assisted 3D reconstruction of the histological sections. This protocol will greatly facilitate a systematic study of the location, pathogenesis, clinical impact, prognosis and prevention of WMHs.

Glutamate signaling in the mature retinal tissue is very important for accurate sensory decoding by retinal neurons and orchestrates the fine-tuned output from the retina to higher-order centers at the cerebral cortex. In this study, we show that glutamate induces a rapid extracellular-regulated kinase and cAMP-responsive element binding protein (CREB) phosphorylation in cultured developing retinal neurons. This process is reliant on alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors and nitric oxide (NO) signaling and independent of NMDA receptors activation, as it is blocked by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate antagonists as well as inhibiting NO synthase with NG-nitro-L-arginine methyl ester but not by the NMDA channel blocker dizocilpine maleate. The effect of NO on extracellular-regulated kinase and CREB is mediated by the classical NO/soluble guanylyl cyclase/protein kinase G pathways as it is inhibited by the soluble guanylyl cyclase blocker 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one and the protein kinase G inhibitor KT5823, respectively. Immunocytochemical data suggest that increased CREB phosphorylation in response to glutamate occurs in glial cell nuclei. We also have supporting evidence suggesting that neuronally produced NO directly reaches the glial cells and stimulates CREB phosphorylation. Hence, the results indicate the importance of neuronal-glial communication and glutamate/NO/CREB linkage during retinal development.

In the present communication, a new series of 2-[(phenylmethylene)hydrazono]-4-oxo-3-phenyl-5-thiazolidineacetic acids (2a-p) have been synthesized. Benzaldehyde 4-phenyl-3-thiosemicarbazones substituted (1a-p) were also obtained and used as intermediate to give the title compounds. All synthesized compounds were characterized by IR, (1)H and (13)C NMR. The in vitro anti-Toxoplasma gondii activity of 1a-p and 2a-p was evaluated. The 4-thiazolidinones (2a-p) were screened for their in vitro antimicrobial activity. For anti-Toxoplasma gondii activity, in general, all compounds promoted decreases in the percentage of infected cells leading to parasite elimination. These effects on intracellular parasites also caused a decrease in the mean number of tachyzoites. In addition, most of the 4-thiazolidinones showed more effective toxicity against intracellular parasites, with IC(50) values ranging from 0.05 to 1 mM. According to results of antimicrobial activity, compounds 2f, 2l, and 2p showed best activity against Mycobacterium luteus, 2c was more active against Mycobacterium tuberculosis, and 2g, 2l, and 2n showed same activity as nistatin (standard drug) against Candida sp. (4249).

A malacological survey was carried out at the Soledade Lake, in Ouro Branco, State of Minas Gerais, for the period 1986-1991. A total amount of 46,579 mollusks was collected, and among them seven species corresponding to five families could be found, as follows: 39,176 specimens of Biomphalaria tenagophila; 1,296 B. glabrata; 7 Drepanotrema cimex; 2,527 Physa sp; 417 Lymnaea sp; 92 Pomacea hastrum, and 3,064 specimens of Melanoides tuberculata (Melanniidae = Thiaridae) were collected from March/1990 onwards. Four specimens of B. tenagophila were found to be positive for Schistosoma mansoni.

Mice infected with about 90 cercariae of Schistosoma mansoni (LE strain) were treated during five consecutive days with dexamethasone (50 mg/Kg, subcutaneously), starting on the 42nd day of infection. Groups of five mice were then daily sacrificed from the first day after onset of treatment until the first day after. The perfusion of the portal system was performed and a piece of the intestine was processed for qualitative and quantitative oograms. This treatment carries to larger numbers of eggs in the tissues of treated mice, when compared with untreated groups. No changes were observed in the kinetics of oviposition, as all stages of viable eggs were observed in the tissues of treated and control mice. These data reinforce the hypothesis of a partial blockade of the egg excretion in immunosuppressed mice.