Alteration of DNA Methylation and Epigenetic Scores Associated With Features of Schizophrenia and Common Variant Genetic Risk.

BACKGROUND: Unpacking molecular perturbations associated with features of schizophrenia is a critical step toward understanding phenotypic heterogeneity in this disorder. Recent epigenome-wide association studies have uncovered pervasive dysregulation of DNA methylation in schizophrenia; however, clinical features of the disorder that account for a large proportion of phenotypic variability are relatively underexplored. METHODS: We comprehensively analyzed patterns of DNA methylation in a cohort of 381 individuals with schizophrenia from the deeply phenotyped Australian Schizophrenia Research Bank. Epigenetic changes were investigated in association with cognitive status, age of onset, treatment resistance, Global Assessment of Functioning scores, and common variant polygenic risk scores for schizophrenia. We subsequently explored alterations within genes previously associated with psychiatric illness, phenome-wide epigenetic covariance, and epigenetic scores. RESULTS: Epigenome-wide association studies of the 5 primary traits identified 662 suggestively significant (p < 6.72 × 10-5) differentially methylated probes, with a further 432 revealed after controlling for schizophrenia polygenic risk on the remaining 4 traits. Interestingly, we uncovered many probes within genes associated with a variety of psychiatric conditions as well as significant epigenetic covariance with phenotypes and exposures including acute myocardial infarction, C-reactive protein, and lung cancer. Epigenetic scores for treatment-resistant schizophrenia strikingly exhibited association with clozapine administration, while epigenetic proxies of plasma protein expression, such as CCL17, MMP10, and PRG2, were associated with several features of schizophrenia. CONCLUSIONS: Our findings collectively provide novel evidence suggesting that several features of schizophrenia are associated with alteration of DNA methylation, which may contribute to interindividual phenotypic variation in affected individuals.

HLA-DRB1*15:01 and the MERTK Gene Interact to Selectively Influence the Profile of MERTK-Expressing Monocytes in Both Health and MS.

BACKGROUND AND OBJECTIVES: HLA-DRB1*15:01 (DR15) and MERTK are 2 risk genes for multiple sclerosis (MS). The variant rs7422195 is an expression quantitative trait locus for MERTK in CD14+ monocytes; cells with phagocytic and immunomodulatory potential. We aimed to understand how drivers of disease risk and pathogenesis vary with HLA and MERTK genotype and disease activity. METHODS: We investigated how proportions of monocytes vary with HLA and MERTK genotype and disease activity in MS. CD14+ monocytes were isolated from patients with MS at relapse (n = 40) and 3 months later (n = 23). Healthy controls (HCs) underwent 2 blood collections 3 months apart. Immunophenotypic profiling of monocytes was performed by flow cytometry. Methylation of 35 CpG sites within and near the MERTK gene was assessed in whole blood samples of individuals experiencing their first episode of clinical CNS demyelination (n = 204) and matched HCs (n = 345) using an Illumina EPIC array. RESULTS: DR15-positive patients had lower proportions of CD14+ MERTK+ monocytes than DR15-negative patients, independent of genotype at the MERTK SNP rs7422195. Proportions of CD14+ MERTK+ monocytes were further reduced during relapse in DR15-positive but not DR15-negative patients. Patients homozygous for the major G allele at rs7422195 exhibited higher proportions of CD14+ MERTK+ monocytes at both relapse and remission compared with controls. We observed that increased methylation of the MERTK gene was significantly associated with the presence of DR15. DISCUSSION: DR15 and MERTK genotype independently influence proportions of CD14+ MERTK+ monocytes in MS. We confirmed previous observations that the MERTK risk SNP rs7422195 is associated with altered MERTK expression in monocytes. We identified that expression of MERTK is stratified by disease in people homozygous for the major G allele of rs7422195. The finding that the proportion of CD14+ MERTK+ monocytes is reduced in DR15-positive individuals supports prior data identifying genetic links between these 2 loci in influencing MS risk. DR15 genotype-dependent alterations in methylation of the MERTK gene provides a molecular link between these loci and identifies a potential mechanism by which MERTK expression is influenced by DR15. This links DR15 haplotype to MS susceptibility beyond direct influence on antigen presentation and suggests the need for HLA-based stratification of approaches to MERTK as a therapeutic target.

Evaluation of Cell-Specific Epigenetic Age Acceleration in People With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: In multiple sclerosis (MS), accelerated aging of the immune system (immunosenescence) may be associated with disease onset or drive progression. DNA methylation (DNAm) is an epigenetic factor that varies among lymphocyte subtypes, and cell-specific DNAm is associated with MS. DNAm varies across the life span and can be used to accurately estimate biological age acceleration, which has been linked to a range of morbidities. The objective of this study was to test for cell-specific epigenetic age acceleration (EAA) in people with MS. METHODS: This was a case-control study of EAA using existing DNAm data from several independent previously published studies. Data were included if .idat files from Illumina 450K or EPIC arrays were available for both a case with MS and an age-matched and sex-matched control, from the same study. Multifactor statistical modeling was performed to assess the primary outcome of EAA. We explored the relationship of EAA and MS, including interaction terms to identify immune cell-specific effects. Cell-sorted DNA methylation data from 3 independent datasets were used to validate findings. RESULTS: We used whole blood DNA methylation data from 583 cases with MS and 643 non-MS controls to calculate EAA using the GrimAge algorithm. The MS group exhibited an increased EAA compared with controls (approximately 9 mths, 95% CI 3.6-14.4), p = 0.001). Statistical deconvolution showed that EAA is associated with MS in a B cell-dependent manner (ß int = 1.7, 95% CI 0.3-2.8), p = 0.002), irrespective of B-cell proportions. Validation analysis using 3 independent datasets enriched for B cells showed an EAA increase of 5.1 years in cases with MS compared with that in controls (95% CI 2.8-7.4, p = 5.5 × 10-5). By comparison, there was no EAA difference in MS in a T cell-enriched dataset. We found that EAA was attributed to the DNAm surrogates for Beta-2-microglobulin (difference = 47,546, 95% CI 10,067-85,026; p = 7.2 × 10-5), and smoking pack-years (difference = 8.1, 95% CI 1.9-14.2, p = 0.002). DISCUSSION: This study provides compelling evidence that B cells exhibit marked EAA in MS and supports the hypothesis that premature B-cell immune senescence plays a role in MS. Future MS studies should focus on age-related molecular mechanisms in B cells.

p53 Dysregulation in Breast Cancer: Insights on Mutations in the TP53 Network and p53 Isoform Expression.

In breast cancer, p53 expression levels are better predictors of outcome and chemotherapy response than TP53 mutation. Several molecular mechanisms that modulate p53 levels and functions, including p53 isoform expression, have been described, and may contribute to deregulated p53 activities and worse cancer outcomes. In this study, TP53 and regulators of the p53 pathway were sequenced by targeted next-generation sequencing in a cohort of 137 invasive ductal carcinomas and associations between the identified sequence variants, and p53 and p53 isoform expression were explored. The results demonstrate significant variability in levels of p53 isoform expression and TP53 variant types among tumours. We have shown that TP53 truncating and missense mutations modulate p53 levels. Further, intronic mutations, particularly polymorphisms in intron 4, which can affect the translation from the internal TP53 promoter, were associated with increased Δ133p53 levels. Differential expression of p53 and p53 isoforms was associated with the enrichment of sequence variants in p53 interactors BRCA1, PALB2, and CHEK2. Taken together, these results underpin the complexity of p53 and p53 isoform regulation. Furthermore, given the growing evidence associating dysregulated levels of p53 isoforms with cancer progression, certain TP53 sequence variants that show strong links to p53 isoform expression may advance the field of prognostic biomarker study in breast cancer.

Detection of germline variants with pathogenic potential in 48 patients with familial colorectal cancer by using whole exome sequencing.

BACKGROUND: Hereditary genetic mutations causing predisposition to colorectal cancer are accountable for approximately 30% of all colorectal cancer cases. However, only a small fraction of these are high penetrant mutations occurring in DNA mismatch repair genes, causing one of several types of familial colorectal cancer (CRC) syndromes. Most of the mutations are low-penetrant variants, contributing to an increased risk of familial colorectal cancer, and they are often found in additional genes and pathways not previously associated with CRC. The aim of this study was to identify such variants, both high-penetrant and low-penetrant ones. METHODS: We performed whole exome sequencing on constitutional DNA extracted from blood of 48 patients suspected of familial colorectal cancer and used multiple in silico prediction tools and available literature-based evidence to detect and investigate genetic variants. RESULTS: We identified several causative and some potentially causative germline variants in genes known for their association with colorectal cancer. In addition, we identified several variants in genes not typically included in relevant gene panels for colorectal cancer, including CFTR, PABPC1 and TYRO3, which may be associated with an increased risk for cancer. CONCLUSIONS: Identification of variants in additional genes that potentially can be associated with familial colorectal cancer indicates a larger genetic spectrum of this disease, not limited only to mismatch repair genes. Usage of multiple in silico tools based on different methods and combined through a consensus approach increases the sensitivity of predictions and narrows down a large list of variants to the ones that are most likely to be significant.

Exome sequencing of familial adenomatous polyposis-like individuals identifies both known and novel causative genes.

Inherited polyposis syndromes are predominantly caused by pathogenic variants in APC and are linked to familial adenomatous polyposis (FAP). However, after clinical screening, 20%-30% of individuals diagnosed with FAP do not carry a pathogenic variant in APC (often categorised as FAP-like). Other known inherited adenomatous polyposis syndromes such as MUTYH, POLD1/E, or NTHL1-associated polyposis only account for, 3 a fraction of the remaining cases. A cohort of 48 individuals clinically diagnosed with a FAP-like phenotype was selected based on a strong family history of colorectal cancer and no previous pathogenic variant found in APC and/or MUTYH, by genetic screening. Using whole exome sequencing, FAP-like patients were found to carry pathogenic variants in MUTYH, APC, POLE and TP53, as well as DNA-repair genes and inflammation related genes. Additionally, a comprehensive assessment of copy number variation revealed two loci of interest that appeared to be associated with polyposis risk. In total, 6 out of 48 polyposis were explained through re-sequencing. This study highlights the potential role of DNA-repair as well as inflammation-related variants towards polyp development.

Targeted sequencing of genes associated with the mismatch repair pathway in patients with endometrial cancer.

Germline variants inactivating the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 cause Lynch syndrome that implies an increased cancer risk, where colon and endometrial cancer are the most frequent. Identification of these pathogenic variants is important to identify endometrial cancer patients with inherited increased risk of new cancers, in order to offer them lifesaving surveillance. However, several other genes are also part of the MMR pathway. It is therefore relevant to search for variants in additional genes that may be associated with cancer risk by including all known genes involved in the MMR pathway. Next-generation sequencing was used to screen 22 genes involved in the MMR pathway in constitutional DNA extracted from full blood from 199 unselected endometrial cancer patients. Bioinformatic pipelines were developed for identification and functional annotation of variants, using several different software tools and custom programs. This facilitated identification of 22 exonic, 4 UTR and 9 intronic variants that could be classified according to pathogenicity. This study has identified several germline variants in genes of the MMR pathway that potentially may be associated with an increased risk for cancer, in particular endometrial cancer, and therefore are relevant for further investigation. We have also developed bioinformatics strategies to analyse targeted sequencing data, including low quality data and genomic regions outside of the protein coding exons of the relevant genes.

Comprehensive mismatch repair gene panel identifies variants in patients with Lynch-like syndrome.

BACKGROUND: Lynch-like syndrome (LLS) represents around 50% of the patients fulfilling the Amsterdam Criteria II/revised Bethesda Guidelines, characterized by a strong family history of Lynch Syndrome (LS) associated cancer, where a causative variant was not identified during genetic testing for LS. METHODS: Using data extracted from a larger gene panel, we have analyzed next-generation sequencing data from 22 mismatch repair (MMR) genes (MSH3, PMS1, MLH3, EXO1, POLD1, POLD3 RFC1, RFC2, RFC3, RFC4, RFC5, PCNA, LIG1, RPA1, RPA2, RPA3, POLD2, POLD4, MLH1, MSH2, MSH6, and PMS2) in 274 LLS patients. Detected variants were annotated and filtered using ANNOVAR and FILTUS software. RESULTS: Thirteen variants were revealed in MLH1, MSH2, and MSH6, all genes previously linked to LS. Five additional genes (EXO1, POLD1, RFC1, RPA1, and MLH3) were found to harbor 11 variants of unknown significance in our sample cohort, two of them being frameshift variants. CONCLUSION: We have shown that other genes associated with the process of DNA MMR have a high probability of being associated with LLS families. These findings indicate that the spectrum of genes that should be tested when considering an entity like Lynch-like syndrome should be expanded so that a more inclusive definition of this entity can be developed.

Use of multigene-panel identifies pathogenic variants in several CRC-predisposing genes in patients previously tested for Lynch Syndrome.

BACKGROUND: Many families with a high burden of colorectal cancer fulfil the clinical criteria for Lynch Syndrome. However, in about half of these families, no germline mutation in the mismatch repair genes known to be associated with this disease can be identified. The aim of this study was to find the genetic cause for the increased colorectal cancer risk in these unsolved cases. MATERIALS AND METHODS: To reach the aim, we designed a gene panel targeting 112 previously known or candidate colorectal cancer susceptibility genes to screen 274 patient samples for mutations. Mutations were validated by Sanger sequencing and, where possible, segregation analysis was performed. RESULTS: We identified 73 interesting variants, of whom 17 were pathogenic and 19 were variants of unknown clinical significance in well-established cancer susceptibility genes. In addition, 37 potentially pathogenic variants in candidate colorectal cancer susceptibility genes were detected. CONCLUSION: In conclusion, we found a promising DNA variant in more than 25 % of the patients, which shows that gene panel testing is a more effective method to identify germline variants in CRC patients compared to a single gene approach.

Effects of lidocaine and magnesium sulfate in attenuating hemodynamic response to tracheal intubation: single-center, prospective, double-blind, randomized study / Os efeitos da lidocaína e do sulfato de magnésio na atenuação da resposta hemodinâmica à intubação orotraqueal: estudo unicêntrico, prospectivo, duplamente encoberto e aleatorizado

Abstract Background and objectives: Hemodynamic response to airway stimuli is a common phenomenon and its management is important to reduce the systemic repercussions. The objective of this study is to compare the efficacy of intravenous magnesium sulfate versus lidocaine on this reflex hemodynamics after laryngoscopy and tracheal intubation. Methods: This single-center, prospective, double-blind, randomized study evaluated 56 patients ASA 1 or 2, aged 18-65 years, scheduled for elective surgeries under general anesthesia with intubation. The patients were allocated into two groups: Group F received 30 mg·kg-1 of magnesium sulphate and Group L, 2 mg·kg-1 of lidocaine, continuous infusion, immediately before the anesthetic induction. Blood pressure (BP), heart rate (HR), and bispectral index (BIS) were measured in both groups at six different times related to administration of the study drugs. Results: In both groups there was an increase in HR and BP after laryngoscopy and intubation, compared to baseline. Group M showed statistically significant increase in the values of systolic and diastolic blood pressure after intubation, which was clinically unimportant. There was no difference in the BIS values between groups. Among patients receiving magnesium sulfate, three (12%) had high blood pressure versus only one among those receiving lidocaine (4%), with no statistical difference. Conclusion: Magnesium sulfate and lidocaine have good efficacy and safety for hemodynamic management in laryngoscopy and intubation.

Resumo Justificativa e objetivos: A resposta hemodinâmica aos estímulos das vias aéreas é um fenômeno comum e seu controle é importante para diminuir as repercussões sistêmicas. O objetivo deste trabalho é comparar os efeitos da administração endovenosa de sulfato de magnésio versus lidocaína na hemodinâmica desse reflexo após a laringoscopia e intubação orotraqueal. Métodos: Este estudo duplamente encoberto, aleatorizado, unicêntrico e prospectivo avaliou 56 pacientes, ASA 1 ou 2, entre 18 e 65 anos, escalados para cirurgias eletivas sob anestesia geral com intubação orotraqueal. Foram alocados em dois grupos, o M recebeu 30 mg·kg-1 de sulfato de magnésio e o L, 2 mg·kg-1 de lidocaína, em infusão contínua, imediatamente antes da indução anestésica. Os valores de pressão arterial (PA), frequência cardíaca (FC) e índice biespectral (BIS) foram aferidos nos dois grupos em seis momentos relacionados com a administração dos fármacos do estudo. Resultados: Em ambos os grupos houve aumento na FC e PA após a laringoscopia e intubação, em relação aos valores basais. No Grupo M observou-se elevação estatisticamente significativa, mas clinicamente pouco importante, nos valores das pressões arteriais sistólica e diastólica após a intubação. Não houve diferença nos valores de BIS entre os grupos. Dos pacientes que receberam o sulfato de magnésio, 3 (12%) apresentaram episódio de hipertensão, ao passo que apenas um dos que receberam lidocaína (4%) apresentou esse sinal, sem diferença estatística. Conclusão: Sulfato de magnésio e a lidocaína apresentam boa eficácia e segurança no controle hemodinâmico à laringoscopia e intubação.

Effects of lidocaine and magnesium sulfate in attenuating hemodynamic response to tracheal intubation: single-center, prospective, double-blind, randomized study.

BACKGROUND AND OBJECTIVES: Hemodynamic response to airway stimuli is a common phenomenon and its management is important to reduce the systemic repercussions. The objective of this study is to compare the efficacy of intravenous magnesium sulfate versus lidocaine on this reflex hemodynamics after laryngoscopy and tracheal intubation. METHODS: This single-center, prospective, double-blind, randomized study evaluated 56 patients ASA 1 or 2, aged 18-65 years, scheduled for elective surgeries under general anesthesia with intubation. The patients were allocated into two groups: Group F received 30mg·kg-1 of magnesium sulphate and Group L, 2mg·kg-1 of lidocaine, continuous infusion, immediately before the anesthetic induction. Blood pressure (BP), heart rate (HR), and bispectral index (BIS) were measured in both groups at six different times related to administration of the study drugs. RESULTS: In both groups there was an increase in HR and BP after laryngoscopy and intubation, compared to baseline. Group M showed statistically significant increase in the values of systolic and diastolic blood pressure after intubation, which was clinically unimportant. There was no difference in the BIS values between groups. Among patients receiving magnesium sulfate, three (12%) had high blood pressure versus only one among those receiving lidocaine (4%), with no statistical difference. CONCLUSION: Magnesium sulfate and lidocaine have good efficacy and safety for hemodynamic management in laryngoscopy and intubation.

Bionomy of two flies of sanitary and forensic importance: Peckia (Sarcodexia) lambens (Wiedemann) and Oxysarcodexia amorosa (Schiner) (Diptera, Sarcophagidae)

ABSTRACTThis study aims to elucidate the bionomy of Peckia(Sarcodexia) lambens and Oxysarcodexia amorosa to provide data for medical, veterinary and forensic entomology analyses. We analyzed larval stage duration (L1–L3), weight of the mature larvae (L3), pupal stage duration, L1–adult duration, adult emergence and viability of larvae and adults of both species. Larval viability of P. (S.) lambens was 82% and the mean duration of the larval stage was 3.51 ± 0.99 days. The mature larvae had a mean weight of 33.67 ± 7.13 mg. The mean duration of the pupal stage was 8.26 ± 0.93 days and the mean duration of the L1–adult was 11.53 ± 1.22 days. Mean lifespan for females and males was 39.33 ± 1.52 and 57.33 ± 4.72 days, respectively. Larval viability of O. amorosa was 76% and mean duration of larval stage was 3.51 ± 0.64 days. Mature larvae had a mean weight of 28.28 ± 3.38 mg. Mean duration of the pupal stage was 10.14 ± 0.63 days and mean duration of the L1–adult was 13.60 ± 0.69 days. Mean lifespan for females and males was 83.66 ± 15.94 and 84.00 ± 19.97 days, respectively. Oxysarcodexia amorosa showed a L1–adult stage longer than P. (S.) lambens; however both species showed low viability. O. amorosa laid more larvae than P. (S.) lambens, this fact may occur because O. amorosa had longer life duration.

Modelos de regressão para estimação da massa do cacho de bananeira CV. prata anã / Regression models to estimate the mass of the bunch of banana tree CV. prata anã

Objetivou-se com este trabalho desenvolver um modelo matemático para estimar a massa do cacho (MC) de bananeira 'Prata Anã', utilizando características morfológicas das plantas. As equações de regressão linear múltiplas foram determinadas considerando-se a massa real do cacho (MC) como variável dependente e como variáveis independentes, a largura da terceira folha (LF), número de folhas (NF), diâmetro do cacho (DC) e número de bananas por cacho (NB). O modelo linear múltiplo de regressão que melhor estimou a massa do cacho da bananeira 'Prata Anã' ao nível de 5% de significância com R2 de 0,58 foi a equação, MC = -10,96 + 0,176*(DC) + 0,0983*(NB) + 0,0928*(LF) + 0,2216*(NF).

The objective of this work was to develop a mathematician model to estimate the mass of the bunch (MC) of banana cultivar Prata Anã, using dimensions of morphological characteristics of plants. The multiple linear regressions were determined considering the actual mass of the bunch (MC) as the dependent variable and independent variables as the width of the third leaf (LF), number of leaves at tree (NF), diameter of the bunch (DC) and number of bananas per bunch (NB). The multiple linear model that best estimated mass of the bunch to the banana 'Prata Anã' at 5% level of significance was 58% with R2 of the equation, MC = -10,96 + 0,176 * (DC) + 0,0983 * ( NB) + 0,0928 * (LF) + 0,2216 * (NC).

Caracterização morfológica e bionomia de dípteros muscóides (sarcophagidae) de importância sanitária e forense / Morphological and bionomics dipteran Muscoid (Sarcophagidae) of sanitary and forensic importance

Os muscóides da família Sarcophagidae além de serem importantes vetores mecânicos e atuarem como agentes irritantes e espoliadores, assim como produtores de miíases ao homem e animais, também representam um importante papel como indicadores forenses. Com o conhecimento de seu ciclo biológico, as larvas depositadas por esses insetos podem ser utilizadas na datação do intervalo pós-morte (IPM). A família Sarcophagidae é descrita como uma das que apresentam um maior potencial informativo para análises forenses. Este trabalho objetiva estudar pela primeira vez a bionomia de Sarcodexia lambens e Oxysarcodexia amorosa, bem como fazer a primeira caracterização morfologica através da microscopia eletrônica de varredura da espécie O. amorosa. Para o estudo de bionomia, as colônias foram estabelecidas a partir de adultos capturados no campus da FIOCRUZ. Foram analisados: peso de larvas maduras, período larval e pupal, fase de neolarva a adulto e emergência de adultos. Foi analisada a viabilidade das larvas e dos adultos ao longo do experimento. O estudo do potencial biótico e da longevidade da espécie foi realizado para se obter as curvas de sobrevivência. Para a análise através do microscópio eletrônico de varredura, as larvas foram lavadas com solução salina e fixadas em uma solução de glutaraldeído a 2,5(por cento), em tampão cacodilato de sódio 0,1M, pH 7,2 durante uma hora. No mesmo tampão foi utilizado tetróxido de ósmio a 1(por cento) para realizar a pós -fixação. Séries crescentes de acetona foram utilizadas para que ocorresse a desidratação e depois, as amostras foram submetidas ao método de secagem pelo ponto crítico, utilizando CO 2. Para que pudesse ocorrer a visualização no microscópio eletrônico de varredura, as amostras foram montadas em fita condutora de carbono, em suportes metálicos e cobertos por ouro. Para S. lambens, a viabilidade larval foi de 82(por cento) e o período de L1 até L3 foi de 3,51(mais ou menos)0,99 dias. As larvas L3 iniciaram o processo de pupa com peso em média de 33,67(mais ou menos)7,13mg. O período pupal durou em média 8,26(mais ou menos)0,93 dias e tive um aviabilidade de 65,24(por cento). O tempo de larva a adulto teve uma média de 11,53(mais ou menos)1,22 dias e 54,50(por cento) de viabilidade. A longevidade média das fêmeas foi de 39,33(mais ou menos)1,52 dias e a dos machos de 57,33(mais ou menos)4,72 dias. Para O. amorosa, a viabilidade larval foi de 76(por cento). O período de larval foi de 3,51(mais ou menos)0,64 dias. As L3 iniciaram o processo de pupação com peso médio de 28,28(mais ou menos)3,38mg. A viabilidade pupal foi de 88,15(por cento) com média de emergência de 10,14(mais ou menos)0,63 dias. A porcentagem de machos e fêmeas foi de 52,98(por cento) e de 47,01(por cento), respectivamente. O tempo de neolarva a adulto apresentou média de 13,60(mais ou menos)0,69 dias e viabilidade de 67(por cento). A longevidade média da espécie foi de 85,33(mais ou menos)18,82 dias.

Variabilidade espacial da textura de um Argissolo Vermelho Amarelo sob cultivo de pastagem e vegetação nativa / Spatial variability of the texture in a Red-Yellow Ultisol under pasture and nature vegetation crop

O conhecimento da variabilidade espacial dos atributos de um solo sob diferentes coberturas auxilia o estudo das alterações ocorridas em razão do manejo. O objetivo deste trabalho foi determinar, com uso da estatística clássica e geoestatística, a variabilidade espacial das frações texturais de um solo cultivado com pastagem e vegetação nativa. Amostras de solo foram coletadas na profundidade de 0-0,20m, nos pontos de cruzamento de uma malha, com intervalos regulares de 10m, totalizando 64 pontos em cada área. Na área de pastagem, as frações areia grossa e total apresentaram valores médios maiores em relação à vegetação nativa e correlações negativas com as altitudes dos pontos amostrais nas duas áreas. Todas as frações texturais apresentaram dependência espacial de moderada a alta nas duas áreas e com o patamar definido, com exceção da areia fina e do silte na pastagem. Grande parte dessa variabilidade ocorre em função da erosão hídrica.

The study of the spatial variability of soil attributes under different crop helps the study of changes due the management. This research was carried out to determine spatial variability the particle-size distribution, using of the classic statistic and geostatistics, of a soil cultivated with pasture and native vegetation. Soil samples were collected in the layer 0-0.20m, at the crossing points of a regular grid with 10m-intervals, summing up 64 samples points in each area. In the pasture area the fractions of coarse and total sand presented larger mean values in relation to the native vegetation, and negative correlation with the altitude of the points samples in the two areas. All of the fractions presented moderate to high spatial dependence in the two areas and with the defined still, with exception of the fine sand and the silt in the pasture. Much of this variability occurs as a function of water erosion.

Thoracoscopy in the treatment of pleural empyema in pediatric patients.

OBJECTIVE: To evaluate the results of thoracoscopy for the treatment of pleural empyema in pediatric patients. METHODS: A retrospective study of 117 patients who underwent mediastinoscopy or video-assisted thoracoscopy for pleural empyema treatment. General anesthesia and single-lumen oral intubation were used. Surgery was indicated when there was pleural effusion and no clinical and radiological response to clinical treatment (antibiotics, physiotherapy and thoracocentesis) or severe sepsis, together with loculated pleural effusion (confirmed through ultrasound or computed tomography of the chest). RESULTS: Between February of 1983 and July of 2006, 117 thoracoscopies were performed in patients ranging in age from 5 months to 17 years (mean, 4 years). Mean time for thoracic drainage was 9 days (range, 2-33 days), and mean period of hospitalization was 16.4 days (range, 4 to 49 days). One patient (0.8%) died after surgery, and persistent fistula was observed in 33 patients (28%). In 7 cases (6%), open thoracotomy with pulmonary decortication was performed due to the disposition of the empyema. CONCLUSIONS: Management of pleural empyema in this age bracket is still controversial, and surgical indication is often delayed, particularly when there are multiple loculations or severe sepsis. Early thoracoscopy yields a better clinical outcome for pediatric patients with pleural empyema, with apparent decreased morbidity and mortality, earlier chest tube removal, earlier hospital discharge and improved response to antibiotic therapy.

Toracoscopia no tratamento do empiema pleural em pacientes pediátricos / Thoracoscopy in the treatment of pleural empyema in pediatric patients

OBJETIVO: Apresentar resultados obtidos com a toracoscopia no tratamento do empiema pleural em pacientes pediátricos. MÉTODOS: Foram avaliados 117 empiemas pleurais, utilizando-se o mediastinoscópio ou a videotoracoscopia, com anestesia geral e sonda de intubação simples. As indicações para a intervenção cirúrgica foram: derrame pleural com ausência de resposta clínica e radiológica ao tratamento clínico (antibióticos, fisioterapia e toracocentese) ou sepse grave, e derrame pleural loculado (documentado por ultrassonografia ou tomografia computadorizada do tórax). RESULTADOS: De fevereiro de 1983 a julho de 2006, 117 toracoscopias foram realizadas em pacientes com idade entre 5 meses e 17 anos (média, 4 anos). O tempo médio de permanência do dreno torácico foi de 9 dias (2 a 33), e o tempo de internação hospitalar foi de 16,44 dias (4 a 49). Houve apenas um óbito (0,8 por cento), e 33 pacientes (28 por cento) tiveram como complicação fístula aérea prolongada. Em 7 pacientes (6 por cento), houve necessidade de conversão para toracotomia com decorticação pulmonar em decorrência da organização do empiema. CONCLUSÕES: Não existe consenso para o tratamento do empiema pleural nesta faixa etária. A terapêutica cirúrgica é geralmente requisitada tardiamente no curso da doença, particularmente quando já existem múltiplas loculações ou quadro séptico grave. A toracoscopia indicada mais precocemente no tratamento do empiema pleural em pacientes pediátricos proporcionou uma melhor resposta à terapêutica clínica, aparentemente reduzindo o índice de morbi-mortalidade, o tempo de permanência do dreno torácico, o tempo de internação hospitalar e o tempo de antibioticoterapia.

OBJECTIVE: To evaluate the results of thoracoscopy for the treatment of pleural empyema in pediatric patients. METHODS: A retrospective study of 117 patients who underwent mediastinoscopy or video-assisted thoracoscopy for pleural empyema treatment. General anesthesia and single-lumen oral intubation were used. Surgery was indicated when there was pleural effusion and no clinical and radiological response to clinical treatment (antibiotics, physiotherapy and thoracocentesis) or severe sepsis, together with loculated pleural effusion (confirmed through ultrasound or computed tomography of the chest). RESULTS: Between February of 1983 and July of 2006, 117 thoracoscopies were performed in patients ranging in age from 5 months to 17 years (mean, 4 years). Mean time for thoracic drainage was 9 days (range, 2-33 days), and mean period of hospitalization was 16.4 days (range, 4 to 49 days). One patient (0.8 percent) died after surgery, and persistent fistula was observed in 33 patients (28 percent). In 7 cases (6 percent), open thoracotomy with pulmonary decortication was performed due to the disposition of the empyema. CONCLUSIONS: Management of pleural empyema in this age bracket is still controversial, and surgical indication is often delayed, particularly when there are multiple loculations or severe sepsis. Early thoracoscopy yields a better clinical outcome for pediatric patients with pleural empyema, with apparent decreased morbidity and mortality, earlier chest tube removal, earlier hospital discharge and improved response to antibiotic therapy.

Influence of cyclosporine A on mucociliary system after lung transplantation in rats

PURPOSE: To investigate the function of the bronchial mucociliary system in transplanted rat lungs with and without the influence of immunosuppression. METHODS: Thirty-six rats underwent single-lung transplantation and were divided into two groups, one of which received cyclosporine treatment, and the control group which did not. Cyclosporine was administered subcutaneously in doses of 10 mg/kg daily. The rats were sacrificed 2, 15 or 30 days after transplantation. In situ bronchial mucociliary transport (MCT) and ciliary beat frequency (CBF) were determined proximal and distal to the bronchial anastomosis. RESULTS: Significant progressive improvement on MCT, proximal and distal to the anastomotic site, was also found in the cyclosporine-treated group at 15 and 30 days (p<0.01). No significant change in MCT was found in the control group. CBF behavior in the two groups. Histological analysis showed that rejection was significantly higher in the control group (p<0.05). CONCLUSION: Cyclosporine has a positive influence on bronchial mucociliary transport but not on CBF due to the effect of the rejection mechanism.

OBJETIVO: Investigar a função do sistema mucociliar em ratos transplantados sob a influência de imunossupressores. MÉTODOS: Trinta e seis ratos foram submetidos ao transplante pulmonar unilateral e divididos em dois grupos, onde um grupo foi tratado com ciclosporina e outro foi controle. Administrada ciclosporina por via subcutânea na dose de 10 mg/kg diariamente. Os ratos foram sacrificados 2, 15 e 30 dias após o transplante pulmonar. O transporte mucociliar brônquico (TMC) in situ e a freqüência de batimento ciliar (FBC) foram analisados na porção proximal e distal à anastomose brônquica. Realizada correlação dos achados com parâmetros gasométricos e histologia. RESULTADOS: Foi encontrada melhora progressiva e significante no TMC na região proximal e distal a anastomose no grupo que recebeu ciclosporina em 15 e 30 dias (p<0,01). Não houve diferença na FBC nos dois grupos estudados. A análise histológica mostrou que a rejeição foi significantemente maior no grupo controle (p<0,05). A oxigenação foi melhor nos animais que receberam a ciclosporina. CONCLUSÃO: A ciclosporina exerceu influência positiva no transporte mucociliar brônquico, provavelmente por sua ação imunossupressora.

Modelo experimental de enfisema pulmonar em ratos induzido por papaína / Papain-induced experimental pulmonary emphysema model in rats

Objetivo: Com a finalidade de estabelecer uma linha de pesquisa em cirurgia redutora de volume pulmonar, foi proposta a reprodução de um modelo experimental de enfisema em ratos através da instilação intratraqueal de papaína. Métodos: Foi feita a instilação orotraqueal de papaína (20mg/kg) dissolvida em 3,5ml/kg de solução fisiológica a 0,9 por cento. Após 40 dias da instilação, os animais foram submetidos a mecânica ventilatória, com medidas de elastância e resistência do sistema respiratório, e sacrificados com retirada dos pulmões. O tecido pulmonar dos animais foi analisado qualitativamente com coloração de hematoxilina-eosina e submetido à análise morfométrica com medida do diâmetro alveolar médio. O tecido pulmonar foi também submetido à coloração de resorcina-fucsina, para identificação de fibras elásticas, que foram quantificadas em septos alveolares através de análise digital de imagem. Resultados: A análise histológica dos pulmões dos animais submetidos à instilação de papaína mostrou um enfisema pan-acinar, com rotura de septos alveolares e hiperdistensão alveolar. A análise morfométrica revelou médias superiores de diâmetro alveolar médio nos pulmões dos animais submetidos à papaína (149,08mim e 100,56mim), em comparação com o grupo de solução fisiológica (64,08mim e 75,90mim). A quantificação de fibras elásticas de septos alveolares de animais tratados com papaína foi 70 por cento menor do que a de animais submetidos à solução fisiológica. A mecânica ventilatória não mostrou diferença na resistência do sistema respiratório de animais submetidos à papaína ou à solução fisiológica. Já no caso da elastância do sistema respiratório, esta foi menor nos animais do grupo com papaína, em comparação com o grupo com solução fisiológica, demonstrando comportamento funcional do grupo com papaína compatível com enfisema pulmonar, apresentando diminuição da capacidade de recolhimento elástico do tecido pulmonar. Conclusão: Foi possível reproduzir um modelo experimental de enfisema pulmonar pan-acinar em ratos, através da instilação de papaína pela árvore respiratória, com comprovação funcional e morfológica