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Capsaicin, an agonist of TRPV1, evokes intracellular [Ca 2+ ] transients and glutamate release from perfused trigeminal ganglion. The spider toxin PnTx3-5, native or recombinant is more potent than the selective TRPV1 blocker SB-366791 with IC 50 of 47 ± 0.18 nM, 45 ± 1.18 nM and 390 ± 5.1 nM in the same experimental conditions. PnTx3-5 is thus more potent than the selective TRPV1 blocker SB-366791. PnTx3-5 (40 nM) and SB-366791 (3 μM) also inhibited the capsaicin-induced increase in intracellular Ca 2+ in HEK293 cells transfected with TRPV1 by 75 ± 16% and 84 ± 3.2%, respectively. In HEK293 cells transfected with TRPA1, cinnamaldehyde (30 μM) generated an increase in intracellular Ca 2+ that was blocked by the TRPA1 antagonist HC-030031 (10 μM, 89% inhibition), but not by PnTx3-5 (40 nM), indicating selectivity of the toxin for TRPV1. In whole-cell patch-clamp experiments on HEK293 cells transfected with TRPV1, capsaicin (10 μM) generated inward currents that were blocked by SB-366791 and by both native and recombinant PnTx3-5 by 47 ± 1.4%; 54 ± 7.8% and 56 ± 9.0%, respectively. Intradermal injection of capsaicin into the rat left vibrissa induced nociceptive behavior that was blocked by pre-injection with either SB-366791 (3 nmol/site i.d., 83.3 ± 7.2% inhibition) or PnTx3-5 (100 fmol/site, 89 ± 8.4% inhibition). We conclude that both native and recombinant PnTx3-5 are potent TRPV1 receptor antagonists with antinociceptive action on pain behavior evoked by capsaicin., (Copyright © 2019. Published by Elsevier Ltd.)

Guavas are tropical climacteric fruit with a short postharvest shelf life at room temperature. This study aims to extend the shelf life of red guavas 'Pedro Sato' using edible coatings of hydroxypropyl methylcellulose (HPMC) and beeswax (BW) at concentrations of 10%, 20%, and 40% (dry basis). Coated and uncoated guavas were stored for 8 days at 21 °C and assessed every 2 days. The HPMC + BW produced a modified atmosphere around the fruit, delaying ripening process. The coatings reduced loss of mass, maintained green color, and increased firmness compared to the control fruit. The uncoated fruit had 6 days of shelf life. The treatment with HPMC + 20% BW provided the best maintenance of fruit quality. On the eighth day, fruit with this coating showed the same physicochemical characteristics of control fruit in the second day of storage, which represents a gain of 6 days in the shelf life of guavas 'Pedro Sato'., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Allgrove syndrome (AS), also known as triple-A syndrome, is a rare disorder characterized by alacrima, achalasia, adrenal insufficiency, and other manifestations such as problems related to growth, puberty, and neuropsychological development. Although the genetics of this disorder have been studied extensively in recent decades, clinical information is still lacking., Methods: We present a unique case of AS from which we have gained significant insight into its clinical course, especially the management of hypoglycemia., Results: The patient initially presented with altered mental status at age 3 which was found to be due to hypoglycemia. Laboratory values confirmed primary adrenal insufficiency with isolated glucocorticoid deficiency. With additional history of alacrima, a genetic test was obtained which confirmed the diagnosis of AS. For over 10 years, we have been following her growth, puberty, and development. We experienced some challenges in managing her hypoglycemia initially. Certain metabolic effects of steroid overdose were noted. To resolve this problem, we found dextrose supplementation quite effective., Conclusion: The rarity and isolated glucocorticoid deficiency of AS pose clinical challenges for initial diagnosis. Hypoglycemia associated with alacrima should alert the suspicion of AS. Management of hypoglycemia in AS is complicated by achalasia and may benefit from incorporation of both glucocorticoid and dextrose supplementation to prevent side effects of steroid overdose., Competing Interests: DISCLOSURE The authors have no multiplicity of interest to disclose., (Copyright © 2019 AACE.)

Staphylococcus hominis is part of the normal human microbiome. Two subspecies, S. hominis hominis (Shh) and S. hominis novobiosepticus (Shn), have clinical significance. Forty-nine S. hominis isolates were analyzed by the MicroScan automated system, SDS-PAGE and MALDI-TOF methods, followed by partial sequencing of the 16S rDNA gene. The trehalose fermentation test, disk diffusion and broth microdilution tests were used to identify (novobiocin test) and access the susceptibility to oxacillin and vancomycin of isolates. The SCCmec elements and genomic diversity were evaluated by PCR and PFGE methods, respectively. Profiles of 28 (57%; 8 Shh and 20 Shn) isolates corroborated with the results found in all the applied methods of identification. The remaining 21 (43%) isolates were phenotypically identified as Shh by MicroScan; however, they were identified as Shn by SDS-PAGE and mass spectral, and confirmed by 16S rDNA sequencing. Among 41 isolates identified as Shn by the molecular and mass spectrometry methods, 19 (41%) were novobiocin-sensitive, and the trehalose test indicated 11 positive isolates, which are considered atypical phenotypic results for this subspecies. In addition, 92.7% of the isolates identified as Shn by these methods carried mecA gene, while only 12.5% of the Shh isolates were positive. Together, the results highlighted the SDS-PAGE and MALDI-TOF MS methods as promising tools for discriminating S. hominis subspecies.

Background: The chromosome 3q29 microdeletion syndrome is characterized by a clinical phenotype that includes behavioral features consistent with autism and attention deficit hyperactivity disorder, mild to moderate developmental delay, language-based learning disabilities, and/or dysmorphic features. In addition, recent data suggest that adults with chromosome 3q29 microdeletions have a significantly increased risk for psychosis and neuropsychiatric phenotypes., Case Presentation: We report a 3-year-old male with global developmental delay, anemia, and mild dysmorphic facial features. Clinical chromosomal microarray (CMA) testing of the proband detected a heterozygous 1.21 Mb deletion at chromosome 3q29, consistent with a diagnosis of the 3q29 microdeletion syndrome. Interestingly, subsequent parental testing determined that the pathogenic deletion was inherited from his otherwise healthy mother who had a history of learning disabilities. The chromosome 3q29 microdeletion was not detected in the healthy older sibling of the proband by CMA testing, nor was it prenatally detected in a subsequent maternal pregnancy., Conclusion: Our report highlights the 3q29 microdeletion syndrome as an illustrative example of the importance of a molecular diagnosis for families that harbor pathogenic copy number aberrations with variable expressivity, in particular those that also impart an increased risk for adult onset neuropsychiatric phenotypes.

Introduction: Fabry disease (FD) is a disorder caused by mutations in the gene encoding for lysosomal enzyme α-galactosidase A (α-GAL). Reduced α-GAL activity leads to progressive accumulation of globotriaosylceramide (Gb3), also known as CD77. The recent report of increased expression of CD77 in blood cells of patients with FD indicated that this molecule can be used as a potential marker for monitoring enzyme replacement therapy (ERT)., Objective: The purpose of this study was to evaluate the CD77 levels throughout ERT in FD patients (V269M mutation)., Methods: We evaluated the fluctuations in PBMC (peripheral blood mononuclear cell) membrane CD77 expression in FD patients undergoing ERT and correlated these levels with those observed in different cell types., Results: A greater CD77 expression was found in phagocytes of patients compared to controls at baseline. Interestingly, the variability in CD77 levels is larger in patients at baseline (340 - 1619 MIF) and after 12 months of ERT (240 - 530 MIF) compared with the control group (131 - 331 MFI). Furthermore, by analyzing the levels of CD77 in phagocytes from patients throughout ERT, we found a constant decrease in CD77 levels., Conclusion: The increased CD77 levels in the phagocytes of Fabry carriers together with the decrease in CD77 levels throughout ERT suggest that measuring CD77 levels in phagocytes is a promising tool for monitoring the response to ERT in FD.

Background/aim: The aim of this study was to test and validate a new model of extrusive luxation trauma on maxillary first molars of rats., Material and Methods: Forty adult male rats (Rattus norvegicus albinus, Wistar; weight = 230-250 g), 45 days old, were divided into eight groups (n = 5): control groups, in which animals were not subjected to any procedure and waited 1 day (GC1D) or 3 days (GC3D) for euthanasia, and experimental groups, in which animals were subjected to forces of 1100cN, 1300cN, or 1500cN and waited 1 or 3 days for euthanasia (GT1100/1D, GT1100/3D, GT1300/1D, GT1300/3D, GT1500/1D, GT1500/3D). In animals of the experimental groups, trauma was produced by an extrusive force in maxillary first right molars. Four-micrometer serial cuts stained with hematoxylin and eosin (HE) were made. Descriptive microscopic analysis of first upper right molar and semi-quantitative analysis (scores 1 to 4) of intensity of acute and chronic inflammation and vascular changes in the periodontal ligament and active and inactive external root resorption were conducted. The distribution of scores in the groups was compared using the Freeman-Halton extension of Fisher's exact test. The significance level was 5%., Results: It was observed that vascular disorders (bleeding) on the periodontal ligament became more evident with increasing extrusive force., Conclusions: This new method was capable of generating histological changes, proving its secure application in this research area. The 1500cN force produced more damage on the periodontal ligament., Clinical Relevance: The validation of a new experimental method can produce more reliable evidence in further research.

Many studies have confirmed the merits of metformin to treat type 2 diabetes, but few studies have addressed its effect on the respiratory system. Moreover, vascular endothelial growth factor (VEGF) is critical to many lung functions. In this way, we evaluated the metformin impact on the lung in treated obese Swiss mice, induced by postnatal overnutrition. Glucose and insulin were detected and the insulin resistance index (HOMA) was calculated; inflammatory cells and nitrite/nitrate concentration (NOx) was quantified from bronchoalveolar lavage, collagen and lung VEGF-a was analysed in the lung tissue and lung mechanics were evaluated by methacholine-induced bronchoconstriction. Values of glucose, insulin, HOMA; VEGF-a and collagen demonstrate the partial ability of metformin to improve the effects of obesity. However, metformin is ineffective in re-establishing the inflammation, shows no effects on NOx and does not restore bronchoconstriction in obese mice. In conclusion, metformińs beneficial effects on lung are questionable in the postnatal overnutrition model of obesity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We investigated the effects of chronic administration of crude hydroalcoholic extract (CHE) and crude acetone extract (CAE) obtained from leaves of Eugenia brasiliensis species on hypertriglyceridemia and oxidative stress caused by the chronic administration of coconut oil. Rats received CHE or CAE (50, 100 or 150mg/kg, orally) for 30days, plus coconut oil (2mL, orally) or saline for 15th. Triglyceride levels, liver cell lipid accumulation, thiobarbituric acid reactive substances (TBA-RS), total sulfhydryl content and the activities of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were evaluated in the blood and liver of rats. Results showed that chronic administration of CHE or CAE was able to prevent hypertriglyceridemia and decrease the lipid droplets in liver cells, as well as the increase in TBA-RS, the reduction in total sulfhydryl content and CAT activity in the blood and prevent total or partial the increase in CAT and reduction in SOD and GSH-Px activities in the liver. These findings indicate that both extracts may have hypolipidemic and antioxidant effects., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

We, herein, investigated the in vitro effects of argininic acid on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content and on the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the blood, kidney and liver of 60-day-old rats. We also verified the influence of the antioxidants (each at 1.0mM) trolox and ascorbic acid, as well as of N G -nitro-l-arginine methyl ester (L-NAME) at 1.0mM, a nitric oxide synthase inhibitor, on the effects elicited by argininic acid on the parameters tested. The liver, renal cortex and renal medulla were homogenized in 10vol (1:10w/v) of 20mM sodium phosphate buffer, pH 7.4, containing 140mM KCl; and erythrocytes and plasma were prepared from whole blood samples obtained from rats. For in vitro experiments, the samples were pre-incubated for 1h at 37°C in the presence of argininic acid at final concentrations of 0.1, 1.0 and 5.0μM. Control experiments were performed without the addition of argininic acid. Results showed that argininic acid (5.0μM) enhanced CAT and SOD activities and decreased GSH-Px activity in the erythrocytes, increased CAT and decreased GSH-Px activities in the renal cortex and decreased CAT and SOD activities in the renal medulla of 60-day-old rats, as compared to the control group. Antioxidants and/or L-NAME prevented most of the alterations caused by argininic acid on the oxidative stress parameters evaluated. Data suggest that argininic acid alters antioxidant defenses in the blood and kidney of rats; however, in the presence of antioxidants and L-NAME, most of these alterations in oxidative stress were prevented. These findings suggest that oxidative stress may be make an important contribution to the damage caused by argininic acid in hyperargininemic patients and that treatment with antioxidants may be beneficial in this pathology., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Aim: To evaluate the effect of silymarin on the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (γGT) in patients with liver diseases., Methods: A systematic review with meta-analysis of ramdomized and controlled clinical trials was performed, evaluating the effects of sylimarin in patients with hepatic diseases, published by January 31, 2016. Clinical trials were sought on the basis of The Cochrane Central Register of Controlled Trials in the Cochrane Library, PubMed/Medline, Scopus, Web of Science, Lilacs and Clinical Trials. The trials with adult and elderly patients of both sexes, with Liver Diseases who took oral silymarin supplementation, as extract or isolated, as well as Silymarin combined with other nutrients, were included. The trials should provide information about the intervention, such as dosages and detailing of the product used, besides the mean and standard deviation of serum levels of ALT, AST and γGT of the baseline and at the end of the intervention., Results: An amount of 10904 publications were identified. From those, only 17 were included in the systematic review and 6 in the meta-analysis, according to the used selection criteria. In this meta-analysis, the results indicated a reduction of 0.26 IU/mL (95%CI: -0.46-0.07, P = 0.007) at the level of ALT and 0.53 IU/mL (95%CI: -0.74-0.32, P = 0.000) at the serum levels of AST after using the silymarin, both, statistically significant, but with no clinical relevance. There was no significant change in the γGT levels. Subgroup analyzes were also performed for the biochemical markers in relation to the type of intervention, whether silymarin isolated or associated with other nutrients and the time of intervention (whether ≥ 6 mo or < 6 mo). Significant differences were not found. The evaluated studies presented a high degree of heterogeneity and low methodological quality in the carried out analysis., Conclusion: Silymarin minimally reduced, but without clinical relevance, the serum levels of ALT and AST. It is necessary to carry out studies with more appropriate methodological designs., Competing Interests: Conflict-of-interest statement: The authors deny any conflict of interest.

Background:: The hypertriglyceridemic waist (HTW) phenotype is defined as the simultaneous presence of increased waist circumference (WC) and serum triglycerides (TG) levels and it has been associated with cardiometabolic risk in children and adolescents., Objective:: The objective was to evaluate the influence of HTW phenotype in the fasting glycemia and blood pressure in children and adolescents over one-year follow-up period., Methods:: It is a cohort study involving 492 children and adolescents from 7 to 15 years old, both genders, who were submitted to anthropometric, biochemical and clinical evaluation at the baseline, and also after 6 and 12 months of follow-up. Generalized Estimating Equation (GEE) models were calculated to evaluate the longitudinal influence of the HTW phenotype in the glycemia and blood pressure over one-year., Results:: It was observed a prevalence of 10.6% (n = 52) of HTW phenotype in the students. The GEE models identified that students with HTW phenotype had an increase of 3.87 mg/dl in the fasting glycemia mean (CI: 1.68-6.05) and of 3.67mmHg in the systolic blood pressure (SBP) mean (CI: 1.55-6.08) over one-year follow-up, after adjusting for confounding variables., Conclusions:: The results of this study suggest that HTW phenotype is a risk factor for longitudinal changes in glycemia and SBP in children and adolescents over one-year follow-up period., Fundamento:: O fenótipo de cintura hipertrigliceridêmica (CHT) é definido como a presença simultânea de circunferência de cintura (CC) e níveis séricos de triglicérides (TG) aumentados e tem sido associado com risco cardiometabólico em crianças e adolescentes., Objetivo:: Avaliar a influência do fenótipo CHT na glicemia de jejum e na pressão arterial em crianças e adolescentes em um período de acompanhamento de um ano., Métodos:: Trata-se de um estudo de coorte envolvendo 492 crianças e adolescentes de 7 a 15 anos de ambos os sexos, que foram submetidos à avaliação antropométrica, bioquímica e clínica no início e também após 6 e 12 meses de seguimento. Os modelos de Equação de Estimulação Generalizada (GEE) foram calculados para avaliar a influência longitudinal do fenótipo CHT na glicemia e na pressão arterial ao longo de um ano., Resultados:: Foi observada uma prevalência de 10,6% (n = 52) do fenótipo CHT nos estudantes. Os modelos GEE identificaram que os estudantes com fenótipo CHT apresentaram aumento de 3,87 mg/dl na média de glicemia em jejum (IC: 1,68-6,05) e de 3,67 mmHg na pressão arterial sistólica media (PAS) (IC: 1,55-6,08) depois de um ano de acompanhamento, após ajuste para variáveis de confusão., Conclusões:: Os resultados deste estudo sugerem que o fenótipo CHT é um fator de risco para alterações longitudinais da glicemia e da PAS em crianças e adolescentes em um período de um ano de seguimento.

Objective: translating and transculturally adapting the Clinical Competence Questionnaire to Brazilian senior undergraduate Nursing students, as well as measuring psychometric properties of the questionnaire., Method: a methodological study carried out in six steps: translation of the Clinical Competence Questionnaire instrument, consensus of the translations, back-translation, analysis by an expert committee, pre-testing and then presentation of the cross-cultural adaptation process to the developers. Psychometric properties were measured using Cronbach's alpha, intraclass correlation coefficient and content validity index., Results: the instrument was translated, transculturally adapted and its final version consisted of 48 items. Cronbach's alpha coefficient was 0.90, and the agreement index of the items was 99% for students and 98% for evaluators., Conclusion: the Clinical Competence Questionnaire was translated and adapted to Brazilian students, and the psychometric properties of the Portuguese version of the questionnaire presented satisfactory internal consistency regarding the studied sample.

The relative quantitative real-time expression of two expressed sequence tags (ESTs) codifying for key enzymes in nitrogen metabolism in maize, nitrate reductase (ZmNR), and glutamine synthetase (ZmGln1-3) was performed for genotypes inoculated with Azospirillum brasilense. Two commercial single-cross hybrids (AG7098 and 2B707) and two experimental synthetic varieties (V2 and V4) were raised under controlled greenhouse conditions, in six treatment groups corresponding to different forms of inoculation and different levels of nitrogen application by top-dressing. The genotypes presented distinct responses to inoculation with A. brasilense. Increases in the expression of ZmNR were observed for the hybrids, while V4 only displayed a greater level of expression when the plants received nitrogenous fertilization by top-dressing and there was no inoculation. The expression of the ZmGln1-3EST was induced by A. brasilense in the hybrids and the variety V4. In contrast, the variety V2 did not respond to inoculation.

The objective of this study was to evaluate the relationship between agronomic traits and physiological traits of seeds in segregating soybean populations by canonical correlation analysis. Seven populations and two commercial cultivars in three generations were used: F 3 plants and F 4 seeds; F 4 plants and F 5 seeds, and F 4 seeds and plants. The following agronomic traits (group I) were evaluated: number of days to maturity, plant height at maturity, insertion height of first pod, number of pods, grain yield, and oil content. The physiological quality of seeds (group II) was evaluated using germination, accelerated aging, emergence, and emergence rate index tests. The results showed that agronomic traits and physiological traits of seeds are not independent. Intergroup associations were established by the first canonical pair for the generation of F 3 plants and F 4 seeds, especially between more productive plants with a larger pod number and high oil content and seeds with a high germination percentage and emergence rate. For the generation of F 4 plants and F 5 seeds, the first canonical pair indicated an association between reduced maturity cycle, seeds with a high emergence percentage and a high percentage of normal seedlings after accelerated aging. According to the second canonical pair, more productive and taller plants were associated with seed vigor. For the generation of F 4 seeds and plants, the associations established by the first canonical pair occurred between seed vigor and more productive plants with high oil content and reduced maturity cycle, and those established by the second canonical pair between seeds of high physiological quality and tall plants.

We evaluated the in vitro effects of galactose at 0.1, 3.0, 5.0 and 10.0 mM on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content, protein carbonyl content, on the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and on acetylcholinesterase (AChE) activity in the cerebral cortex, cerebellum and hippocampus of rats. We also investigated the influence of the antioxidants (each at 1 mM), α-tocopherol, ascorbic acid and glutathione, on the effects elicited by galactose on the parameters tested. Results showed that galactose, at a concentration of 3.0 mM, enhanced TBA-RS levels in the hippocampus, cerebral cortex and cerebellum of rats. In the cerebral cortex, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and protein carbonyl content, and at 10.0 mM increased CAT activity and decreased AChE activity. In the cerebellum, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS, SOD and GSH-Px activities. In the hippocampus, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and CAT activity and at 10.0 mM decreased GSH-Px. Data showed that at the pathologically high concentration (greater than 5.0 mM), galactose induces lipid peroxidation, protein carbonylation, alters antioxidant defenses in the cerebrum, and also alters cholinesterase activity. Trolox, ascorbic acid and glutathione addition prevented the majority of alterations in oxidative stress parameters and the decrease in AChE activity that were caused by galactose. Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by galactose.

Interview with chemist and geneticist Flávio Lewgoy, who was also an expert criminal and environmental investigator. Lewgoy was at the center of important struggles for human health and environmental quality in Rio Grande do Sul, and was one of the people behind state (1982) and federal (1989) laws governing pesticide use. He believed he had a duty to use scientific knowledge to support his positions on environmental activism and saw this activity as an ethical commitment, a way of paying back society for the education he received in public institutions.

Methicillin-resistant Staphylococcus aureus (MRSA) carrying SCCmec type IV has emerged in hospitals worldwide. The aim of this study was to evaluate phenotypic and molecular characteristics of antimicrobial resistance in MRSA SCCmec IV isolates, presenting different genetic backgrounds, isolated from hospitals in Rio de Janeiro. The antimicrobial resistance of 128 S. aureus type IV isolates from 11 hospitals was characterized by the disk diffusion test and minimum inhibitory concentration (MIC) test. Mutations in parC gene, which encodes ciprofloxacin resistance, and genes associated with macrolide-lincosamide-streptogramin B (MLS b ) resistance were also investigated. MRSA isolates belonging to USA400/ST1 (60 isolates), USA800/ST5 (40), USA1100/ST30 (13), and other 11 (15) lineages were mainly resistant to erythromycin (68%), ciprofloxacin (56%), and clindamycin (50%). The highest antimicrobial resistance rates were found among USA400 isolates (p < 0.05). The majority of them (90%) carried only the erm(C) gene and mainly presented two mutation types in the parC gene. The msr(A) gene was most frequently found among USA800 isolates (p < 0.05). Among MRSA type IV isolates from Rio de Janeiro hospitals, multiresistance, including mutations in parC gene, was associated to the USA400/ST1, while the msr(A) gene was associated with USA800/ST5 isolates, highlighting that these lineages could have more potential to persist in a hospital environment.

Owing to the narrow genetic basis of soybean (Glycine max), the incorporation of new sources of germplasm is indispensable when searching for alleles that contribute to a greater diversity of varieties. The alternative is plant introduction, which may increase genetic variability within breeding programs. Multivariate techniques are important tools to study genetic diversity and allow the precise elucidation of variability in a set of genotypes of interest. The agro-morphological traits of 93 soybean accessions from various continents were analyzed in order to assess the genetic diversity present, and to highlight important traits. The experimental design was incomplete blocks (Alpha lattice, 8 x 12) with three replicates. Nine agro-morphological traits were analyzed, and principal component analysis and cluster analysis were performed, the latter by Ward's method. The dendrogram obtained contained eight subgroups, confirming the genetic diversity among the accessions and revealing similarities between 11 national genotypes. The geographical origin of the accessions was not always related to the clusters. The traits evaluated, and the methods used, facilitated the distinction and characterization of genotypes between and within groups, and could be used in Brazilian soybean breeding programs.

Fabry nephropathy is a major cause of morbidity and premature death in patients with Fabry disease (FD), a rare X-linked lysosomal storage disorder. Gb3, the main substrate of α-galactosidase A (α-Gal A), progressively accumulates within cells in a variety of tissues. Establishment of cell models has been useful as a tool for testing hypotheses of disease pathogenesis. We applied CRISPR/Cas9 genome editing technology to the GLA gene to develop human kidney cell models of FD in human immortalized podocytes, which are the main affected renal cell type. Our podocytes lack detectable α-Gal A activity and have increased levels of Gb3. To explore different pathways that could have distinct patterns of activation under conditions of α-gal A deficiency, we used a high-throughput antibody array to perform phosphorylation profiling of CRISPR/Cas9-edited and control podocytes. Changes in both total protein levels and in phosphorylation status per site were observed. Analysis of our candidate proteins suggests that multiple signaling pathways are impaired in FD., (Copyright © 2016 the American Physiological Society.)

The Rh blood group system is one of the most complex, polymorphic and immunogenic blood group systems in humans. Some individuals produce a weak or a partial D as a result of RHD and RHCE gene conversion events and RHD point mutations. Because the incidence of RHD variants differs considerably among ethnic groups, the objective of this study was to establish the frequency of blood donors carrying some weak and partial RHD, at the molecular level, in 400 blood donors from the North/Northwest of the state of Parana, Southern Brazil. Another 30 blood donors whose RhD typing results in serology were inconclusive were also included. In this mixed Brazilian population, the most frequent weak D types were 1, 4, 3 and 2 (frequencies of 4.35%, 2.32%, 1.46% and 0.29%, respectively; total of 8.41%) and partial D was found in 2.90% of samples carrying the RHD gene. For samples with inconclusive RhD typing, 53.33% of them presented weak and partial RHD, and 43.75% had concomitantly more than one RHD variant. Our results demonstrate the presence of Caucasian and African D variants. This knowledge can contribute to the safety of transfusion strategies in this ethnic admixture population., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Sexually transmitted diseases (STDs) are the main global cause of acute illness and death and represent a high socioeconomic cost. Undergraduate students are highly exposed to STDs. The research developed at UNICAMP sought to quantify and generate self-perception of knowledge(or lack thereof) about STDs, as well as evaluate the interest of the students in a course on the topic. The data collection instrument was a questionnaire sent electronically to students about to graduate at the end of 2011 and to freshmen in 2012. The questionnaire was answered by 1,448 seniors and 371 freshmen. Twenty percent of seniors and 38% of freshmen had no sexual activity. Among sexually active students, 26.9% had no regular partner and 28.2% more than two partners per year. The condom was used by 99% of students, but less than 20% used them appropriately. About 80% were unaware that condoms do not provide protection outside the barrier area; they intended to read more about STDs and learnt something about the subject. Nearly half of the students considered that a course should be offered to all undergraduates. These findings will be of use in defining strategies for prevention and the teaching tool could be used in other learning environments.

Background: - The fourth most frequent tumor in the world, colorectal cancer is commonly diagnosed at an advanced stage., Objective: - To analyze factors that interfere in the diagnosis of colorectal cancer in users of the Public Health System treated at an universitary hospital in Curitiba, Paraná State, Brazil., Methods: - Cross-sectional, quantitative and descriptive study with 120 patients treated at the institution between 2012 and 2013. Data collection, carried out by means of medical record appointments and patients' interviews, addressed sociodemographic variables; clinical profile; timespan between symptoms, examination, diagnosis, treatment onset and difficulties encountered. Statistical analyses were performed by means of Stata 8.0., Results: - Abdominal pain was the most frequent complaint and rectal bleeding presented the highest chance of advanced colorectal cancer diagnosis. From 52.5% of patients with late diagnosis of colorectal cancer, 81% reported difficulties in the health system., Conclusion: - Results suggest that late diagnosis is due to symptom absence in the early stage of the disease, patients' lack of perception about the severity of the symptoms, need of better of health teams to search early diagnosis. Educational interventions are deemed necessary to the population and health teams, besides actions prioritizing the access to diagnostic testing for serious illnesses.

The in vivo neuroprotective effect of PhTx3-4, a spider toxin N-P/Q calcium channel blocker, was studied in a rat model of NMDA-induced injury of the retina. NMDA (N-Methyl-D-Aspartate)-induced retinal injury in rats reduced the b-wave amplitude by 62% ± 3.6%, indicating the severity of the insult. PhTx3-4 treatment increased the amplitude of the b-wave, which was almost equivalent to the control retinas that were not submitted to injury. The PhTx3-4 functional protection of the retinas recorded on the ERG also was observed in the neuroprotection of retinal cells. NMDA-induced injury reduced live cells in the retina layers and the highest reduction, 84%, was in the ganglion cell layer. Notably, PhTx3-4 treatment caused a remarkable reduction of dead cells in the retina layers, and the highest neuroprotective effect was in the ganglion cells layer. NMDA-induced cytotoxicity of the retina increased the release of glutamate, reactive oxygen species (ROS) production and oxidative stress. PhTx3-4 treatment reduced glutamate release, ROS production and oxidative stress measured by malondialdehyde. Thus, we presented for the first time evidence of in vivo neuroprotection from NMDA-induced retinal injury by PhTx3-4 (-ctenitoxin-Pn3a), a spider toxin that blocks N-P/Q calcium channels.

Introduction: Fabry disease is a lysosomal storage disorder due to abnormalities in the GLA gene (Xq22). Such changes result in the reduction/absence of activity of the lysosome enzyme α-GAL, whose function is to metabolize globotriaosylceramide (Gb3). Renal disease is a major clinical outcome of the accumulation of Gb3. Podocyte injury is thought to be a major contributor to the progressive loss of the renal function and may be found altered even before the onset of microalbuminuria., Objective: The aim of this study was to quantify the urinary excretion of podocytes in Fabry disease patients (V269M, n = 14) and healthy controls (n = 40), and to correlate podocyturia with the variables gender, age, time of therapy and albumin: creatinine ratio (ACR)., Methods: Urinary podocytes were stained using immunofluorescence to podocalyxin and DAPi. The number of podocalyxin-positive cells was quantified and the average number was taken (normal range 0-0.6 podocytes/mL)., Results: The average number of podocytes in the urine of Fabry disease patients was significantly higher than in healthy controls (p < 0.0001). We observed a positive correlation between podocyturia and ACR (p = 0.004; (r2 = 0.6417). We found no correlation between podocyturia and gender, age or duration of therapy., Conclusion: Podocyturia is an important parameter in the assessment of renal disease in general, and it may serve as an additional early tool for monitoring Fabry disease nephropathy even before changes in ACR are seen. This may prove to be a useful tool to assess disease progression in patients expected to have a more aggressive phenotype.

Anthropometry has been widely used in different fields, providing relevant information for medicine, ergonomics and biometric applications. However, the existent solutions present marked disadvantages, reducing the employment of this type of evaluation. Studies have been conducted in order to easily determine anthropometric measures considering data provided by low-cost sensors, such as the Microsoft Kinect. In this work, a methodology is proposed and implemented for estimating anthropometric measures considering the information acquired with this sensor. The measures obtained with this method were compared with the ones from a validation system, Qualisys. Comparing the relative errors determined with state-of-art references, for some of the estimated measures, lower errors were verified and a more complete characterization of the whole body structure was achieved.

Although non-accidental injuries (NAI) are more common in cases of unexplained fractures than rare disorders such as osteogenesis imperfecta (OI), ruling out OI and other medical causes of fracture is always indicated. The majority of OI patients can be diagnosed with the help of family history, physical examination, and radiographic findings. In particular, there are a few radiological findings which are seen more commonly in NAI than in OI which may help guide clinician considerations regarding the probability of either of these diagnoses. At the same time, molecular testing still merits careful consideration in cases with unexplained fractures without obvious additional signs of abuse., (© 2015 Wiley Periodicals, Inc.)

Background: Some research indicates that physicians do not dominate the expected dermatological content for the proper exercise of the profession. This fact compromises their diagnostic and therapeutic performance, generating unnecessary costs., Objective: The aim of this study was to evaluate the relevance of Dermatology and the knowledge acquired in the specialty during the undergraduate course in clinical practice of graduates at the State University of Campinas Medical School (FCM/UNICAMP)., Method: A questionnaire with 22 closed questions and two open ones was electronically sent to physicians who had graduated more than 10 years ago and others for less than 10 years. In the first group, physicians were trained by the same curriculum and in the second group there were subjects trained by the old and the new curriculum., Results: Of the 126 respondents, 83% had completed a specialization course. Among all, 82% did not study dermatology after graduation. The majority considered that Dermatology has high relevance in clinical practice, regardless of the group. There was a statistically significant difference between non-dermatologist doctors graduated for more than 10 years and those graduated for less than 10 years regarding confidence about lesion diagnosis, diagnostic investigation and treatment of skin diseases. Physicians who have graduated for a longer time feel more insecure in relation to patients with dermatoses. Concerning contributions offered by graduation program completion they prioritized outpatient care, ability to diagnose, knowledge of pathology, research and knowledge of lesions., Conclusion: This study has shown that Dermatology is relevant in medical practice and more recent graduates from the FCM/UNICAMP feel less insecure when treating a patient with dermatoses.

In the present study, we evaluated the in vitro effects of homoarginine (hArg) at 1, 10 and 20 µM on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content and on the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in plasma, erythrocytes, kidney and liver of rats (60 days old). We also investigated the influence of the antioxidants (each at 1 mM) α-tocopherol and ascorbic acid, as well as of the nitric oxide synthase inhibitor N (G)-nitro-L-arginine methyl ester (L-NAME) at 1 mM, on the effects elicited by hArg on the parameters tested. In plasma, hArg at concentrations of 10 and 20 μM decreased moderately the total sulfhydryl content. At 20 µM, hArg enhanced moderately TBA-RS in the plasma. In plasma, the effects of hArg (20 µM) on TBA-RS and total thiol content were abolished by α-tocopherol, ascorbic acid and L-NAME. At all concentrations tested, hArg did not exert any effect on CAT, SOD or GSH-Px activity in the erythrocytes. In the kidney, hArg exerted effects only at 20 µM and in a different manner: TBA-RS levels increased and total thiol content and CAT activity decreased, while SOD and GSH-Px activity increased. In the renal medulla, α-tocopherol and ascorbic acid but not L-NAME abolished the effects of hArg (20 µM) on TBA-RS, while all agents inhibited the hArg-induced increase in SOD activity. In the renal cortex, α-tocopherol, ascorbic acid and L-NAME abolished the effects of hArg (20 µM) on the total sulfhydryl content and GSH-Px activity, but L-NAME did not reverse the inhibitory effects of hArg on CAT activity. In the liver, no effects of hArg were observed of all biomarkers measured. At the pathologically high concentration of 20 µM, as it may occur in plasma in hyperargininemia, hArg may enhance lipid peroxidation and thiol oxidation and inhibit CAT activity, but may increase SOD and GSH-Px activity predominantly in the kidney.

The aim of this study was to determine the effects of previous administration of metyrapone (met) on the acute lung injury (ALI) induced by caecal ligation and puncture (CLP) and to explore met's relationship with endogenous glucocorticoids (GCs) as measured by inflammatory, oxidative and functional parameters. One hundred and thirty-five Wistar rats were divided into three main groups: Control (Naïve), Sham and CLP. The animals received pretreatment one hour before surgery. The Naïve group did not undergo any procedure or pretreatment. The Sham group only had the caecum exposed and was pretreated with saline. The CLP group was divided into three pretreatments: metyrapone (CLP met 50 mg/kg i.p.), dexamethasone (CLP dex 0.5 mg/kg i.p.) or saline (CLP sal equivalent volume of 0.9% NaCl). Analyses were performed after 6 and 24 h of sepsis. Previous administration of met significantly increased inflammatory cells, as well as myeloperoxidase (MPO) activity in the lung tissue and alveolar collapsed area, with consequent impairment of respiratory mechanics being observed compared to Sham and Naïve; CLP sal exhibited similar results to those of met. The met reduced corticosterone (CCT) levels and dramatically increased hydrogen peroxide (H2 O2 ) levels in the lung tissue compared to CLP sal. Our results suggest that previous administration of met may have contributed to increased pulmonary oxidative stress and increased mortality by mechanisms dependent of endogenous GC., (© 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.)

Edible mushrooms are high nutritional value foods, which contain proteins, fibers, minerals, vitamins, and carbohydrates. Among their carbohydrates are some polysaccharides with recognized therapeutic effects. It was reported in this manuscript the structural characterization and antinociceptive and anti-inflammatory activities of an exopolysaccharide (EPS) produced by Pleurotus sajor-caju. The purified EPS was a mannogalactan (PEIsR), which was composed by mannose (37.0%), galactose (39.7%), and 3-O-methyl-galactose (23.3%). The polysaccharide was purified by freeze-thawing and dialysis, and it was characterized by GC-MS analysis and NMR spectroscopy. The mannogalactan is constituted by a main chain of (1 → 6)-linked α-D-Galp and 3-O-methyl-α-D-Galp units. Some of the α-D-Galp units were substituted at O-2 by non-reducing end units of β-D-Manp. According to the literature review conducted, this is the first time that a methylated polysaccharide was observed on EPS of P. sajor-caju. The mannogalactan was able to reduce the nociception, in vivo, in the writhing and formalin tests and also reduced the carrageenan-induced paw edema, which indicates that it could be an effective antinociceptive and anti-inflammatory agent., (Copyright © 2015. Published by Elsevier B.V.)

Unlabelled: The effects of intrathecal administration of the toxins Phα1β and ω-conotoxin MVIIA were investigated in visceral nociception induced by an intraperitoneal injection of acetic acid and an intracolonic application of capsaicin. The pretreatments for 2h with the toxins reduced the number of writhes or nociceptive behaviors compared with the control mice. Phα1β administration resulted in an Imax of 84±6 and an ID50 of 12 (5-27), and ω-conotoxin MVIIA resulted in an Imax of 82±9 and an ID50 of 11 (4-35) in the contortions induced by the intraperitoneal injection of acetic acid. The administration of Phα1β resulted in an Imax of 64±4 and an ID50 of 18 (9-38), and ω-conotoxin MVIIA resulted in an Imax of 71±9 and an ID50 of 9 (1-83) in the contortions induced by intracolonic capsaicin administration. Phα1β (100/site) or ω-conotoxin MVIIA (30pmol/site) pretreatments caused a reduction in CSF glutamate release in mice intraperitoneally injected with acetic acid or treated with intracolonic capsaicin. The toxin pretreatments reduced the ROS levels induced by intraperitoneal acetic acid injection. Phα1β, but not ω-conotoxin MVIIA, reduced significantly the ROS levels induced by intracolonic capsaicin administration., Perspective: Phα1β is a ω-toxin with high therapeutic index and a broader action on calcium channels. It shows analgesic effect in several rodents' models of pain, including visceral pain, suggesting that this toxin has the potential to be used in clinical setting as a drug in the control of persistent pathological pain., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Unlabelled: Opioids are standard therapy for the treatment of pain; however, adverse effects limit their use. Voltage-gated calcium channel blockers may be used to increase opioid analgesia, but their effect on opioid-induced side effects is little known. Thus, the goal of this study was to evaluate the action of the peptide Phα1β, a voltage-gated calcium channel blocker, on the antinociceptive and adverse effects produced by morphine in mice. A single administration of morphine (3-10 mg/kg) was able to reduce heat nociception as well as decrease gastrointestinal transit. The antinociception caused by a single injection of morphine was slightly increased by an intrathecal injection of Phα1β (30 pmol/site). Repeated treatment with morphine caused tolerance, hyperalgesia, withdrawal syndrome, and constipation, and the Phα1β (.1-30 pmol/site, intrathecal) was able to reverse these effects. Finally, the effects produced by the native form of Phα1β were fully mimicked by a recombinant version of this peptide. Taken together, these data show that Phα1β was effective in potentiating the analgesia caused by a single dose of morphine as well as in reducing tolerance and the adverse effects induced by repeated administration of morphine, indicating its potential use as an adjuvant drug in combination with opioids., Perspective: This article presents preclinical evidence for a useful adjuvant drug in opioid treatment. Phα1β, a peptide calcium channel blocker, could be used not only to potentiate morphine analgesia but also to reduce the adverse effects caused by repeated administration of morphine., (Copyright © 2014. Published by Elsevier Inc.)

This study investigated the effects of Phα1β, pregabalin and diclofenac using an animal model of fibromyalgia (FM). Repeated administration of reserpine (0.25 mg/kg sc) once daily for three consecutive days significantly decreased thermal hyperalgesia, mechanical allodynia, and dopamine and serotonin content in the brain on the 4th day. Phα1β and pregabalin treatment completely reverted the mechanical allodynia and thermal hyperalgesia induced by reserpine treatment on the 4th day, but diclofenac was ineffective. Reserpine treatment significantly increased the immobility time in the forced swim test, which is indicative of depression in the animals. Phα1β, but not pregabalin, reduced the immobility time (56%), suggesting that Phα1β may control persistent pathological pain in FM., (Copyright © 2014. Published by Elsevier Ltd.)

This study investigated the potential relationship between the expression levels of lysosome-associated membrane proteins (LAMP) 1 and 2 and responses to enzyme replacement therapy (ERT) in the members of a single family with Fabry disease (FD). LAMP levels were assessed by flow cytometry in leukocytes from 17 FD patients who received an eight-month course of ERT course and 101 healthy individuals. We found that phagocytic cells from the FD patients had higher expression levels of both LAMP-1 and LAMP-2, relative to the levels in phagocytes from the healthy controls (p=0.001). Furthermore, the LAMP-1 and LAMP-2 levels in phagocytes from the FD carriers continuously decreased with ERT administration to reach levels similar to those in healthy controls. We suggest that LAMP-1 and LAMP-2 could be used as additional markers with which to assess ERT effectiveness in FD., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This study aimed to report the antigen and haplotype frequencies (HFs) of volunteer bone marrow donors (VBMDs) from the state of Piauí who were enrolled in the National Volunteer Bone Marrow Donor Registry (REDOME). The research subjects were 21,943 volunteer bone marrow donors, predominantly young adult women (53.3%). The most frequent allelic group was HLA-A2, followed by -DRB1*13, -DRB1*04, -DRB1*07, -B*15, -B∗35, -B*44, -A*24 and -A*03. Of the 2,704 haplotypes observed, the three most frequent haplotypes were A*29 B*44 DRB1*07 (1.45%), A*01 B*08 DRB1*03 (1.4%) and A*03 B*07 DRB1*15 (0.92%). These three haplotypes were in linkage disequilibrium. PCA showed that 98% of the VBMDs have HLA allele frequencies that are very similar to those from Teresina, the capital city of Piauí. According to the PCA results, these municipalities are distributed with a close proximity to Teresina, which in turn has a close genetic proximity to the Hispanic ethnicity, intermediate proximity to Caucasians and Africans and a distant kinship to Amerindians. The hierarchical proximity of the population of Piauí to the Portuguese and Hispanic populations to shows the strong influence of the latter on the former., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

The aim of this work was to perform a systematic study to detect and quantify the digenetic trematode infections in South American sea lions from the southern Brazilian coast. Twenty-four South American sea lions, Otaria flavescens (Carnivora: Otaridae), were found dead along the coast of Rio Grande do Sul State, Brazil, between June 2010 and September of 2011. Two trematode species were found in the intestines of O. flavescens, i.e., Stephanoprora uruguayense (Digenea: Echinostomatidae) and Ascocotyle (Phagicola) longa (Digenea: Heterophyidae). Ascocotyle (P.) longa reached a prevalence of 33.3% and mean intensity of 248,500, whereas S. uruguayense showed a prevalence of 4.2% and mean intensity of 202. The 2 trematode species infecting sea lions were likely transmitted by feeding on mullets, Mugil platanus, that commonly harbor heterophyid metacercariae. The present work is the first report of digenetic trematodes infecting O. flavescens in Brazil. The high prevalence and mean intensity values of the 2 trematode species infecting sea lions in the present study suggest caution in human consumption of mullets and other fish, which can be infected with the metacercariae of these trematodes known to have zoonotic potential.

Objective: To evaluate the effectiveness of training in surgical techniques in pig feet during medical school., Methods: We conducted a cross-sectional study with 87 volunteer medical students from different graduation semesters, who attended a basic workshop for incisions, sutures, biopsies, flaps, grafts, under direct supervision. Pre and post-training self-administered questionnaires were used., Results: The teaching of sutures, biopsies and ear correction was effective for learning of the minimal skills required for the proposed techniques (p <0.005), as well as excisions and flaps, except grafting (p> 0 97)., Conclusion: The methodological approach and monitoring of techniques' reproduction were adequate. The training offered complemented cutaneous surgical skills of undergraduate medicine students.

Staphylococcus epidermidis in immunocompromised patients can cause bacteremia related to the use of catheter due to biofilm production. There are different phenotypic methods to detect biofilm formation. One method is based on culture in brain heart infusion agar (BHIA) containing sucrose and red Congo dye (original Congo red agar). Our group created a new CRA formula and we have confirmed its capacity to detect biofilm production in 210 S. epidermidis strains, including 76 (36.2%) icaAB gene-positive strains. Other parameters were also evaluated. The new CRA formula that gave the best results was BHIA with sucrose (5%), Congo red (0.08%), NaCl (1.5%), glucose (2%), and vancomycin (0.5 mg/mL) (vancomycin-modified CRA-CRAmod). The CRAmod plus vancomycin may be a promising tool and can help to determine the real participation of S. epidermidis in the infectious process., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Oral leukoplakia is the main potentially malignant oral lesion, and oral squamous cell carcinoma accounts for more than 95% of all malignant neoplasms in the oral cavity. Therefore, the aim of this study was to verify the immunoexpression of nuclear factor κB (NF-κB) and cyclooxygenase-2 (COX-2) proteins in dysplastic oral lesions and oral squamous cell carcinoma. Immunohistochemical reactions were performed on 6 inflammatory fibrous hyperplasia, 28 oral leukoplakia, and 15 oral squamous cell carcinoma paraffin-embedded samples. Immunoperoxidase reaction for NF-κB and COX-2 was applied on the specimens, and the positivity of the reactions was calculated for 1000 epithelial cells. Using the analysis of variance and the Tukey post hoc statistical analyses, a significantly increased immunoexpression for NF-κB was observed when oral squamous cell carcinoma samples were compared with the other groups studied. However, using the Kruskal-Wallis and the Dunn post hoc tests, a statistically significant result for COX-2 expression was obtained only when the moderate dysplasia group was compared with the inflammatory fibrous hyperplasia group. Nuclear factor κB may participate in the malignant phenotype acquisition process of the oral squamous cell carcinoma in its late stages, whereas COX-2 may be involved in the early stages of oral carcinogenesis process., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: The JAK2 46/1 haplotype has recently been described as a major contributing factor to the development of myeloproliferative neoplasm, whether positive or negative forthe JAK2 V617F mutation. The G allele, identified by a single-nucleotide polymorphism known as JAK2 rs10974944, is part of the JAK2 46/1 haplotype. The aim of this study was to verify the association between the presence of the G allele and the development of BCR-ABL-negative chronic myeloproliferative neoplasms in our population., Methods: Blood and oral mucosa swab samples were obtained from 56 patients of two local Brazilian hospitals who had previously been diagnosed with BCR-ABL-negative chronic myeloproliferative neoplasms. Blood samples from 90 local blood donors were used as controls. The presence of the G allele was assessed using a PCR-RFLP assay after extracting DNA from the samples., Results: The presence of the G allele was strongly associated with the presence of BCR-ABL-negative chronic myeloproliferative neoplasms (p = 0.0001; OR = 2.674; 95% CI = 1.630-4.385) in the studied population., Conclusion: In agreement with previous reports, the JAK2 46/1 haplotype, represented in this study by the presence of the G allele, is an important predisposing factor in the oncogenetic development of these neoplasms in our population.

Introduction: Diabetes is a well known risk factor for early and late adverse outcomes in patients undergoing coronary artery bypass graft surgery (CABG); however, few studies have investigated the impact of this risk factor in the group of older patients, especially octogenarians., Objectives: To compare in-hospital mortality and morbidity of diabetic and nondiabetic patients aged > 80 years submitted to CABG., Methods: A total of 140 consecutive cases were studied, of whom 37 (26.4%) were diabetics, in a retrospective cross-sectional study, that included all patients aged > 80 years submitted to isolated/associated CABG. The patients' mean age was 82.5 ± 2.2 years and 55.7% were males., Results: The hospital mortality rate did not significantly differ in multivariate analysis: 16.2% diabetic x 13.6% nondiabetic (P = 0.554), as well as morbidity: 43.2% x 37.9%, respectively (P = 0.533). Regarding to operative morbidity, the occurrence of stroke was significantly higher in diabetic patients in the univariate analysis (10.8% x 1.9%, P = 0.042). In multivariate analysis, however, the incidence of stroke was not associated with the presence of diabetes (P = 0.085), but it was associated with atrial fibrillation (P = 0.044). There was no significant difference related to other complications., Conclusion: In this small consecutive retrospectively analyzed series, there was no significant increase in hospital mortality and morbidity related to diabetes for CABG in octogenarian patients. The impact of the results of this study is limited by the sample size and might be confirmed by future randomized clinical trials.

Wound healing is divided into three phases: inflammatory, proliferative and remodeling. Mast cells participate in all these phases. The aim of the present study was to determine the effects of propolis on the population of mast cells in oral surgical wounds in comparison to the results obtained with dexamethasone. This study was prospective, in vivo, randomized, semiexperimental, quantitative and comparative animal. A circular surgical wound was made on the dorsum of the tongue of 90 hamsters divided into three experimental groups: topical application of 30% propolis alcoholic extract (Group 1); 0.1% dexamethasone in orabase cream (Group 2); and orabase cream alone (Group 3). Applications were performed every 12 h throughout the experiment. The postoperative times for killing of the animals were 1, 3, 7, 14 and 28 days. The Student's t test for independent samples was employed in the statistical analysis. In the inflammatory phase of healing, propolis caused a greater reduction in the number of mast cells on the edge and in the central region of the surgical wound in comparison to dexamethasone. Moreover, the number of mast cells on day 1 was lower in the central region of the wounds treated with the orabase cream alone in comparison to dexamethasone. In conclusion, the anti-inflammatory action of propolis mediated by mast cells was more effective than dexamethasone in the inflammatory phase of healing.

This work characterizes MLS(b) resistance in 39 methicillin-resistant Staphylococcus aureus (MRSA) and 32 Staphylococcus epidermidis (MRSE) isolates. Of 21 erm(A) gene encoding MRSA isolates, 71.4% carried SCCmecIII, whereas of 12 isolates carrying the erm(C) gene, 83.3% carried SCCmecIV. Among the 25 MRSE isolates positive for the erm(C) gene, 80% had SCCmecIV or nontypeable cassettes. Isolates carrying these genes had MIC(90) ≥ 256 μg/mL to erythromycin and clindamycin. The msr(A) gene was associated with a low MIC(90) to these drugs. The erm(A) gene was associated with SCCmecIII in MRSA isolates, whereas the erm(C) gene was associated with SCCmecIV in both MRSA and MRSE isolates., (© 2012 The Societies and Wiley Publishing Asia Pty Ltd.)

Introduction: Fluid overload is a clinical problem frequently related to cardiac and renal dysfunction. The aim of this study was to evaluate fluid overload and changes in serum creatinine as predictors of cardiovascular mortality and morbidity after cardiac surgery., Methods: Patients submitted to heart surgery were prospectively enrolled in this study from September 2010 through August 2011. Clinical and laboratory data were collected from each patient at preoperative and trans-operative moments and fluid overload and creatinine levels were recorded daily after cardiac surgery during their ICU stay. Fluid overload was calculated according to the following formula: (Sum of daily fluid received (L)--total amount of fluid eliminated (L)/preoperative weight (kg) × 100). Preoperative demographic and risk indicators, intra-operative parameters and postoperative information were obtained from medical records. Patients were monitored from surgery until death or discharge from the ICU. We also evaluated the survival status at discharge from the ICU and the length of ICU stay (days) of each patient., Results: A total of 502 patients were enrolled in this study. Both fluid overload and changes in serum creatinine correlated with mortality (odds ratio (OR) 1.59; confidence interval (CI): 95% 1.18 to 2.14, P = 0.002 and OR 2.91; CI: 95% 1.92 to 4.40, P <0.001, respectively). Fluid overload played a more important role in the length of intensive care stay than changes in serum creatinine. Fluid overload (%): b coefficient = 0.17; beta coefficient = 0.55, P <0.001); change in creatinine (mg/dL): b coefficient = 0.01; beta coefficient = 0.11, P = 0.003)., Conclusions: Although both fluid overload and changes in serum creatinine are prognostic markers after cardiac surgery, it seems that progressive fluid overload may be an earlier and more sensitive marker of renal dysfunction affecting heart function and, as such, it would allow earlier intervention and more effective control in post cardiac surgery patients.

We report a case of hepatoblastoma in a 10-year-old girl with mosaic-type trisomy 18. A comprehensive literature review reveals only 2 cases involving mosaic trisomy 18 patients. Our patient underwent an abbreviated chemotherapy course before complete surgical resection. Her hepatoblastoma did not contain cells with trisomy 18. The conservative management approach resulted in a successful outcome; she remains disease free >2 years after surgery. Along with presenting a literature review, this report demonstrates a favorable outcome in a mosaic trisomy 18 child with hepatoblastoma where tumor cells lacked a trisomy 18 karyotype.

In this study, felodipine was incorporated into microparticles prepared with Eudragit® E and it blended with poly(3-hydroxybutyrate) (PHB) using the emulsion-solvent evaporation technique, with the aim of improving the dissolution rate of the drug. The formulation prepared with Eudragit® E showed irregular and fragmented microparticles, with a loading efficiency (LE) of 82.6%. When the microparticles were prepared with a blend of Eudragit® E and PHB, they had a spherical form with a LE of 103.9%. X-ray diffraction and differential thermal analysis indicated a reduction in the crystallinity of felodipine after its incorporation into the microparticles, which caused a significant increase in the felodipine dissolution rate. An investigation into the absorption in rats was carried out using high-performance liquid chromatography analysis of the blood collected 20 and 60 min after the animals were administered felodipine [30 mg/Kg, orally (p.o.)] or felodipine microparticles (30 mg/Kg, p.o.). Animals that were given felodipine showed mean plasmatic levels of 0.0125 (±0.00156) and 0.0240 (±0.0069) μg mL(-1) after 20 and 60 min, respectively, whereas animals that received microparticles containing felodipine showed respective mean plasmatic levels of 0.0651 (±0.0120) and 0.0369 (±0.0145) μg mL(-1) . Our data suggest that the incorporation into microparticles significantly enhanced the release of felodipine, improving its absorption in rats., (Copyright © 2012 Wiley Periodicals, Inc.)

Staphylococcus lugdunensis is an unusually virulent coagulase-negative species, which causes serious infection similar to S. aureus. We evaluated the expression of virulence factors such as S. lugdunensis synergistic haemolysin (SLUSH), fibrinogen-binding protein (Fbl), biofilm production and biofilm-production-related genes in 23 S. lugdunensis clinical isolates and one type strain that had been previously characterized for their genotypes. In addition, the biofilm composition and the ability of isolates to adhere to and invade human epithelial lung cells were also investigated. The PCR method used detected the presence of slush and intercellular adhesin (ica) virulence genes in all isolates. All isolates produced the Fbl protein and, with the exception of the type strain, all isolates produced the SLUSH haemolysin. Fourteen (60.9 %) isolates produced biofilms. The detachment assay, using sodium metaperiodate or proteolytic enzymes to analyse the biofilm composition, showed protein-mediated biofilms in two representative isolates, one for each colony type (rough and smooth). All strongly biofilm-producing isolates, including three with rough colony morphology, had the same prevalent PFGE pattern. However, among the representative strains tested, only the S. lugdunensis isolate that formed rough colonies was able to adhere to and invade A549 cell monolayers in the same quantities as those observed with S. aureus isolates (P = 1.000). No significant adhesion or invasion was observed for the other isolates in comparison with the S. aureus isolate, independent of biofilm production or clonality. Our results could explain the incredible ability of this pathogen to cause infections that are as aggressive as S. aureus. In addition, the ability of S. lugdunensis to adhere to and invade eukaryotic cells was also noticed for isolates with rough colony morphology, reinforcing the increased virulence in this species.

Background: About 10% to 15% of patients undergoing cardiac surgery may develop low cardiac output syndrome in the perioperative period; of this total, 2% require mechanical support for adequate hemodynamic control., Objective: To describe the mortality rates of patients who required the use of IABP in the perioperative or postoperative period of cardiac surgery, identifying preoperative variables associated with a worse outcome, as well as to describe the postoperative complications and medium-term survival., Methods: Retrospective cohort study including 80 consecutive cases between January/2009 and September/ 2011. The patients had on average 62.9 ± 11.3 years and 58.8% were male; 81.3% were hypertensive, 50.0% had prior myocardial infarction and 38.8% has NYHA III/IV heart failure. The mainsurgery performed was isolated coronary artery bypass grafting (37.5%)., Results: Hospital mortality was 53.8% (IC 95%: 42.7-64.9), and cross-clamp time > 90 minutes was an independent predictor of mortality in multivariate analysis (OR 1.52 CI 95%: 1.04-2.22). 71.3% of patients (CI 95%: 61.2-81.4) had at least one additional complication in the perioperative period, with lower limb ischemia observed in 5.0% patients. One-year survival was 43.6%, with a plateau in survival rates after a sharp initial drop, related to hospital mortality., Conclusion: Patients who require IABP comprise a group of very high risk for morbidity and mortality. IABP use, however, enables the recovery of many patients from an evolution that would invariably be fatal, and patients discharged from hospital have a good medium-term survival.

Interstitial deletions of 6q are associated with variable phenotypes, including growth retardation, dysmorphic features, upper limb malformations, and Prader-Willi (PW)-like features. Only a minority of cases in the literature have been characterized with high resolution techniques, making genotype-phenotype correlations difficult. We report 12 individuals with overlapping, 200-kb to 16.4-Mb interstitial deletions within 6q15q22.33 characterized by microarray-based comparative genomic hybridization to better correlate deletion regions with specific phenotypes. Four individuals have a PW-like phenotype, though only two have deletion of SIM1, the candidate gene for this feature. Therefore, other genes on 6q may contribute to this phenotype including multiple genes on 6q16 and our newly proposed candidate, the transcription cofactor gene VGLL2 on 6q22.2. Two individuals present with movement disorders as a major feature, and ataxia is present in a third. The 4.1-Mb 6q22.1q22.2 critical region for movement disorders includes the cerebellar-expressed candidate gene GOPC. Observed brain malformations include thick corpus callosum in two subjects, cerebellar vermal hypoplasia in two subjects, and cerebellar atrophy in one subject. Seven subjects' deletions overlap a ~250-kb cluster of four genes on 6q22.1 including MARCKS, HDAC2, and HS3ST5, which are involved in neural development. Two subjects have only this gene cluster deleted, and one deletion was apparently de novo, suggesting at least one of these genes plays an important role in development. Although the phenotypes associated with 6q deletions can vary, using overlapping deletions to delineate critical regions improves genotype-phenotype correlation for interstitial 6q deletions.