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OBJETIVO: Avaliar a operação para revascularização do miocárdio sem circulação extracorpórea (CEC) em pacientes com importante disfunção ventricular esquerda. MÉTODOS: Foram submetidos a operação para revascularização do miocárdio sem CEC, 405 pacientes com fração de ejeção (FE) abaixo de 35%. A operação foi realizada com auxílio de estabilizador por sucção e ponto de LIMA. As anastomoses distais foram feitas primeiro. RESULTADOS: Foram avaliados 405 pacientes com idade média de 63,4±9,78 anos, sendo 279 do sexo masculino (68,8%). Quanto a fatores de risco, 347 eram hipertensos, 194 tabagistas, 202 dislipidêmicos e 134 diabéticos. Encontravam-se em classe funcional III e IV 260 pacientes. Eram renais crônicos 20 pacientes, em programa de diálise. Foram operados em caráter de emergência 51 pacientes, e 33 já apresentavam operação prévia. A FE média foi de 27,2±3,54%. O EUROSCORE médio foi de 8,46±4,41. O número médio de anastomoses foi 3,03±1,54 por paciente. Necessitaram de balão intraórtico após a indução anestésica 49 pacientes (12%), e 73 (18%) necessitaram de suporte inotrópico no período transoperatório. Quanto a complicações, 2 (0,49%) apresentaram insuficiência renal, 2 apresentaram mediastinite (0,49%), 7 (1,7%) necessitaram de reoperação por sangramento, 5 (1,2%) apresentaram infarto agudo do miocárdio e 70 (17,3%) apresentaram fibrilação atrial. Houve 18 óbitos (4,4%). CONCLUSÃO: Com base nesses dados, concluímos que a operação para revascularização do miocárdio sem circulação extracorpórea em pacientes com disfunção ventricular esquerda é segura e eficaz, sendo uma alternativa para pacientes de alto risco. Os resultados obtidos foram superiores ao previsto pelo EUROSCORE.OBJECTIVE: To assess off-pump myocardial revascularization in patients with significant left ventricular dysfunction. METHODS: Four hundred and five patients with an ejection fraction less than 35% underwent myocardial revascularization without extracorporeal circulation. The procedure was performed with the aid of a suction stabilizer and the LIMA stitch. The distal anastomoses were performed first. RESULTS: A total of 405 patients were evaluated whose mean age was 63.4±9.78 years. Two hundred and seventy-nine patients were men (68.8%). With regard to risk factors, 347 patients were hypertensive, 194 were smokers, 202 were dyslipidemic, and 134 had diabetes. Two hundred and sixty patients were classified as NYHA functional class III and IV. Twenty patients suffered from chronic renal disease and were under dialysis. Fifty-one underwent emergency surgery, and 33 had been previously operated on. The mean ejection fraction was 27.2±3.54%. The mean EuroSCORE was 8.46±4.41. The mean number of anastomoses performed was 3.03±1.54 per patient. Forty-nine patients (12%) needed an intra-aortic balloon inserted after induction of anesthesia, whereas 73 (18%) needed inotropic support during the perioperative period. As to complications, 2 patients (0.49%) had renal failure, 2 had mediastinitis (0.49%), 7 (1.7%) needed to be reoperated because of bleeding, 5 patients (1.2%) suffered acute myocardial infarction, and 70 patients (17.3%) experienced atrial fibrillation. Eighteen (4.4%) patients died. CONCLUSION: Based on the data above, we concluded that myocardial revascularization without extracorporeal circulation in patients with left ventricular dysfunction is a safe and effective technique, and an alternative for high-risk patients. Results obtained were better than those predicted by EuroSCORE.

A leucemia mielóide crônica é uma doença proliferativa do sistema hematopoiético, caracterizada pela expansão clonal de uma célula tronco primitiva e pluripotente denominada "stem cell", que tem a capacidade de se diferenciar em células mielóides, monocíticas, megacariocíticas e células B e T. Em homeostase, existe um equilíbrio entre proliferação, diferenciação e renovação das células tronco, equilíbrio este que se encontra alterado em pacientes com Leucemia mielóide crônica, devido a uma proliferação e diferenciação aumentada e anormal relacionada à atividade de tirosino quinase do produto do gene quimérico BCR/ABL resultante da translocação t(9;22), que se apresenta como marcador da doença. Vários transcritos quiméricos têm sido descritos e acredita-se que a gravidade do quadro clínico dependa do tipo de mRNA gerado. No presente trabalho analisamos 28 amostras de 27 pacientes diagnosticados com Leucemia mielóide crônica. Todos possuíam a translocação t(9;22) e foram analisados para a presença dos transcritos resultantes das fusões b3a2 ou b2a2 por RT-PCR e Nested-PCR, técnicas que se mostraram mais sensíveis para a identificação dos transcritos. Entre os pacientes, 12% apresentaram fusão b3a2, 18% possuíam fusão b2a2 e 32% possuíam os dois tipos de transcritos. A presença de um dos tipos de transcritos, b3a2, parece estar relacionada com contagem de plaquetas acima de 1 milhão/mm³ , reconhecida como característica de mau prognóstico em pacientes com Leucemia mielóide crônica.

Abstract Web services have become a key technology for bioinformatics, since life science databases are globally decentralized and the exponential increase in the amount of available data demands for efficient systems without the need to transfer entire databases for every step of an analysis. However, various incompatibilities among database resources and analysis services make it difficult to connect and integrate these into interoperable workflows. To resolve this situation, we invited domain specialists from web service providers, client software developers, Open Bio* projects, the BioMoby project and researchers of emerging areas where a standard exchange data format is not well established, for an intensive collaboration entitled the BioHackathon 2008. The meeting was hosted by the Database Center for Life Science (DBCLS) and Computational Biology Research Center (CBRC) and was held in Tokyo from February 11th to 15th, 2008. In this report we highlight the work accomplished and the common issues arisen from this event, including the standardization of data exchange formats and services in the emerging fields of glycoinformatics, biological interaction networks, text mining, and phyloinformatics. In addition, common shared object development based on BioSQL, as well as technical challenges in large data management, asynchronous services, and security are discussed. Consequently, we improved interoperability of web services in several fields, however, further cooperation among major database centers and continued collaborative efforts between service providers and software developers are still necessary for an effective advance in bioinformatics web service technologies.

Background: Ovarian clear cell carcinomas (OCCCs) are rare, aggressive and chemoresistant tumors. Geographical and ethnic differences in the incidence of OCCC have been reported with a higher incidence in Asiatic countries. There is a paucity of information regarding OCCC in Latin America (LA) and other countries., Methods: Here, we characterized two cohorts of 33 patients with OCCC from LA (24 from Brazil and 9 from Costa Rica) and a cohort of 27 patients from Spain. Genomic analysis was performed for 26 OCCC using the OncoScan platform. Tumors were classified according to their genomic landscapes into subgroups. Clinical parameters were related to the frequency of genomic aberrations., Results: The median overall survival (OS) was not significantly different between the cohorts. Genomic landscapes were characterized by different homologous recombination deficiency (HRD) levels. No difference in the distribution of genomic landscapes profiles was detected between patients from the different cohorts. OCCCs with MYC-amplified tumors harboring a concomitant loss of a region in chromosome 13q12-q13 that includes the BRCA2 gene had the longest OS. In contrast, patients carrying a high number (> 30) of total copy number (CN) aberrations with no concomitant alterations in MYC and BRCA2 genes presented the shortest OS. Furthermore, amplification of the ASH1L gene was also associated with a shorter OS. Initial-stage OCCCs with early progression were characterized by gains in the JNK1 and MKL1 genes., Conclusions: Our results provide new data from understudied OCCC populations and reveal new potential markers for OCCCs., (© 2023. The Author(s).)

Perimenopause is a transitional state which occurs in women in their mid-life. These women may experience climacteric symptoms that affect their day-to-day life. The aim of the study was to assess and compare climacteric symptoms and their impact on daily lives among employed and unemployed perimenopausal women. A cross-sectional survey was done on 160 rural south Indian women aged 40 to 55 years who were identified as symptomatic of perimenopause as per the Stages of Reproductive Aging Workshop 10+ (STRAW) staging criteria. The study participants were grouped as employed and unemployed. Climacteric symptoms were assessed using Greene Climacteric Scale and climacteric symptoms' impact on daily lives was measured using a structured self-administered questionnaire. Both descriptive and inferential statistics were used to compare the variables between the two groups. The total Greene Climacteric score for unemployed perimenopausal women were found to be significantly higher than the employed group of perimenopausal women (14.5 ± 7.23 versus 12.52 ± 4.9, p  < 0.05). The majority (58.8%) of the employed group had minimum impact whereas; the majority (51.2%) of the unemployed group had an average impact score. There was a strong positive correlation between climacteric symptoms and their impact on the daily lives of perimenopausal women. Employment status is a significant factor in causing variation in the climacteric symptoms. Unemployed perimenopausal women suffered more climacteric symptoms than their employed counterparts.

Objective: To analyze the relationship between the biochemical markers of liver metabolism in different stages of Metabolic Associated Fatty Liver Disease (MAFLD) according to the obesity phenotype., Methodology: This is a cross-sectional study with individuals with class III obesity classified according to the obesity phenotypes proposed by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Biochemical and anthropometric variables were analyzed according to the staging of MAFLD and obesity phenotype., Results: A total of 50 subjects with MAFLD, 62% (n = 31) with steatosis and 38% (n = 19) with steatohepatitis without fibrosis; 36% were classified as metabolically healthy obesity (MHO) and 64% as metabolically unhealthy obesity (MUHO), respectively. Mean values of alkaline phosphatase were 85.44 ± 27.27 vs. 61.92 ± 17.57 ( p  = 0.006); gamma-glutamyl transpeptidase, 25.77 ± 15.36 vs. 30.63 ± 19.49 ( p  = 0.025); and albumin, 3.99 ± 0.34 vs. 4.24 ± 0.23 ( p  = 0.037), were lower and statistically significant in the MHO group with steatosis. The results show when considering individuals with IR, only AP is a predictor of unhealthy phenotype (B-0.934, 0.848- 1.029, p  = 0.031)., Conclusion: MHO individuals with steatosis present lower severe changes related to markers of liver damage and function and AP is considered the predictor of MUHO phenotype.

The circadian clock of mosquitoes can influence physiological and behavioral processes linked to disease transmission. Currently, we know how clock genes are expressed in the head of the Aedes aegypti in different light and temperature regimens, but we still do not know anything about the expression of these genes in the body. The present work aims to contribute to this understanding. We observed that the expression of clock genes in the body of Aedes can be different from that in the head. Additionally, we found that temperature cycles have greater influence on the clock genes of the body of Aedes than light/dark cycles.

Regular physical activity improves physical and mental health. Here we found that the effect of physical activity extends to the next generation. Voluntary wheel running of dams, from postpartum day 2 to weaning, increased the social dominance and reproductive success, but not the physical/metabolic health, of their otherwise sedentary offspring. The individual's own physical activity did not improve dominance status. Maternal exercise did not disrupt maternal care or the maternal and offspring microbiota. Rather, the development of dominance behavior in the offspring of running mothers could be explained by the reduction of LIF, CXCL1, and CXCL2 cytokines in breast milk. These data reveal a cytokine-mediated lactocrine pathway that responds to the mother's postpartum physical activity and programs offspring social dominance. As dominance behaviors are highly relevant to the individual's survival and reproduction, lactocrine programming could be an evolutionary mechanism by which a mother promotes the social rank of her offspring., Competing Interests: Declaration of Interests The authors declare no competing financial interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Neural development is controlled at multiple levels to orchestrate appropriate choices of cell fate and differentiation. Although more attention has been paid to the roles of neural-restricted factors, broadly expressed factors can have compelling impacts on tissue-specific development. Here, we describe in vivo conditional knockout analyses of murine Ars2, which has mostly been studied as a general RNA-processing factor in yeast and cultured cells. Ars2 protein expression is regulated during neural lineage progression, and is required for embryonic neural stem cell (NSC) proliferation. In addition, Ars2 null NSCs can still transition into post-mitotic neurons, but fail to undergo terminal differentiation. Similarly, adult-specific deletion of Ars2 compromises hippocampal neurogenesis and results in specific behavioral defects. To broaden evidence for Ars2 as a chromatin regulator in neural development, we generated Ars2 ChIP-seq data. Notably, Ars2 preferentially occupies DNA enhancers in NSCs, where it colocalizes broadly with NSC regulator SOX2. Ars2 association with chromatin is markedly reduced following NSC differentiation. Altogether, Ars2 is an essential neural regulator that interacts dynamically with DNA and controls neural lineage development., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Transcription factors regulate the molecular, morphological, and physiological characteristics of neurons and generate their impressive cell-type diversity. To gain insight into the general principles that govern how transcription factors regulate cell-type diversity, we used large-scale single-cell RNA sequencing to characterize the extensive cellular diversity in the Drosophila optic lobes. We sequenced 55,000 single cells and assigned them to 52 clusters. We validated and annotated many clusters using RNA sequencing of FACS-sorted single-cell types and cluster-specific genes. To identify transcription factors responsible for inducing specific terminal differentiation features, we generated a "random forest" model, and we showed that the transcription factors Apterous and Traffic-jam are required in many but not all cholinergic and glutamatergic neurons, respectively. In fact, the same terminal characters often can be regulated by different transcription factors in different cell types, arguing for extensive phenotypic convergence. Our data provide a deep understanding of the developmental and functional specification of a complex brain structure., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Parental behavioural traits can be transmitted by non-genetic mechanisms to the offspring. Although trait transmission via sperm has been extensively researched, epidemiological studies indicate the exclusive/prominent maternal transmission of many non-genetic traits. Since maternal conditions impact the offspring during gametogenesis and through fetal/early-postnatal life, the resultant phenotype is likely the aggregate of consecutive germline and somatic effects; a concept that has not been previously studied. Here, we dissected a complex maternally transmitted phenotype, reminiscent of comorbid generalized anxiety/depression, to elementary behaviours/domains and their transmission mechanisms in mice. We show that four anxiety/stress-reactive traits are transmitted via independent iterative-somatic and gametic epigenetic mechanisms across multiple generations. Somatic/gametic transmission alters DNA methylation at enhancers within synaptic genes whose functions can be linked to the behavioural traits. Traits have generation-dependent penetrance and sex specificity resulting in pleiotropy. A transmission-pathway-based concept can refine current inheritance models of psychiatric diseases and facilitate the development of better animal models and new therapeutic approaches.

Although comprehensively described during early neuronal development, the role of DNA methylation/demethylation in neuronal lineage and subtype specification is not well understood. By studying two distinct neuronal progenitors as they differentiate to principal neurons in mouse hippocampus and striatum, we uncovered several principles governing neuronal DNA methylation during brain development. (1) The program consists of three stages: an initial genome-wide methylation during progenitor proliferation is followed by loss of methylation during the transition of regional progenitors to "young" hippocampal/striatal neurons, which is then reversed by gain in methylation during maturation to subtype-specific neurons. (2) At the first two stages, gain and loss of methylation are limited to CpGs, whereas during the third maturation stage, methylation also occurs at non-CpG sites in both lineages. (3) Methylation/demethylation, similar to transcription, are initially highly similar in the two lineages, whereas diversification in methylation and transcription during maturation creates subtype-specific methylation differences. (4) Initially, methylation targets all genomic locations, whereas later, during early and late differentiation, the preferred targets are intronic/intergenic sequences with enhancer-like activity. (5) Differentially methylated genes are enriched in sequential neurodevelopmental functions (such as progenitor proliferation, migration, neuritogenesis, and synaptic transmission); upregulated genes represent current and consecutive stage-specific functions, and downregulated genes represent preceding functions that are no longer required. The main conclusion of our work is that the neuronal methylation/demethylation program is predominantly developmental with minimal lineage specificity, except in the final stage of development when neuron subtype-specific differences also emerge., Significance Statement: Our work is the first to describe a set of relatively simple rules that govern DNA methylation and demethylation in neuronal development in vivo. By dividing neurodevelopment to three major stages and applying rules to each of them, we created a matrix that comprehensively describes DNA methylation/demethylation events in two neuronal lineages, with a total of 10 cell types spanning the entire neurodevelopment. Beyond increasing our understanding of the epigenetic regulation of normal development, our work will be useful in deciphering how environmental perturbations, such as gestational toxins, drugs, stress, infection, and offspring neglect/maltreatment, interfere with the developmental methylation program., (Copyright © 2016 the authors 0270-6474/16/361711-12$15.00/0.)

In mammals, damage to sensory receptor cells (hair cells) of the inner ear results in permanent sensorineural hearing loss. Here, we investigated whether postnatal mouse inner ear progenitor/stem cells (mIESCs) are viable after transplantation into the basal turns of neomycin-injured guinea pig cochleas. We also examined the effects of mIESC transplantation on auditory functions. Eight adult female Cavia porcellus guinea pigs (250-350 g) were deafened by intratympanic neomycin delivery. After 7 days, the animals were randomly divided in two groups. The study group (n=4) received transplantation of LacZ-positive mIESCs in culture medium into the scala tympani. The control group (n=4) received culture medium only. At 2 weeks after transplantation, functional analyses were performed by auditory brainstem response measurement, and the animals were sacrificed. The presence of mIESCs was evaluated by immunohistochemistry of sections of the cochlea from the study group. Non-parametric tests were used for statistical analysis of the data. Intratympanic neomycin delivery damaged hair cells and increased auditory thresholds prior to cell transplantation. There were no significant differences between auditory brainstem thresholds before and after transplantation in individual guinea pigs. Some mIESCs were observed in all scalae of the basal turns of the injured cochleas, and a proportion of these cells expressed the hair cell marker myosin VIIa. Some transplanted mIESCs engrafted in the cochlear basilar membrane. Our study demonstrates that transplanted cells survived and engrafted in the organ of Corti after cochleostomy.