An industrialized diet as a determinant of methylation in the 1F region of the NR3C1 gene promoter.

Background: Dietary composition can modify gene expression, favoring the development of chronic diseases via epigenetic mechanisms. Objective: Our study aimed to investigate the relationship between dietary patterns and NR3C1 gene methylation in users of the Brazilian Public Unified Health System (SUS). Methods: We recruited 250 adult volunteers and evaluated their socioeconomic status, psychosocial characteristics, lifestyle, and anthropometrics. Peripheral blood was collected and evaluated for cortisol levels, glycemia, lipid profile, and insulin resistance; methylation of CpGs 40-47 of the 1F region of the NR3C1 gene was also measured. Factors associated with degree of methylation were evaluated using generalized linear models (p < 0.05). Lifestyle variables and health variables were included as confounding factors. Results: The findings of our cross-sectional study indicated an association between NR3C1 DNA methylation and intake of processed foods. We also observed relevant associations of average NR3C1 DNA across the segment analyzed, methylation in component 1 (40-43), and methylation in component 2 (44-47) with a pattern of consumption of industrialized products in relation to BMI, serum cortisol levels, and lipid profile. These results may indicate a relationship between methylation and metabolic changes related to the stress response. Conclusion: These findings suggest an association of methylation and metabolic alterations with stress response. In addition, the present study highlights the significant role of diet quality as a stress-inducing factor that influences NR3C1 methylation. This relationship is further linked to changes in psychosocial factors, lifestyle choices, and cardiometabolic variables, including glucose levels, insulin resistance, and hyperlipidemia.

SpliceProt 2.0: A Sequence Repository of Human, Mouse, and Rat Proteoforms.

SpliceProt 2.0 is a public proteogenomics database that aims to list the sequence of known proteins and potential new proteoforms in human, mouse, and rat proteomes. This updated repository provides an even broader range of computationally translated proteins and serves, for example, to aid with proteomic validation of splice variants absent from the reference UniProtKB/SwissProt database. We demonstrate the value of SpliceProt 2.0 to predict orthologous proteins between humans and murines based on transcript reconstruction, sequence annotation and detection at the transcriptome and proteome levels. In this release, the annotation data used in the reconstruction of transcripts based on the methodology of ternary matrices were acquired from new databases such as Ensembl, UniProt, and APPRIS. Another innovation implemented in the pipeline is the exclusion of transcripts predicted to be susceptible to degradation through the NMD pathway. Taken together, our repository and its applications represent a valuable resource for the proteogenomics community.

A Critical Review of Analytical Methods for the Quantification of Phthalates Esters in Two Important European Food Products: Olive Oil and Wine.

Phthalic acid esters (PAEs) are a class of chemicals widely used as plasticizers. These compounds, considered toxic, do not bond to the polymeric matrix of plastic and can, therefore, migrate into the surrounding environment, posing a risk to human health. The primary source of human exposure is food, which can become contaminated during cultivation, production, and packaging. Therefore, it is imperative to control and regulate this exposure. This review covers the analytical methods used for their determination in two economically significant products: olive oil and wine. Additionally, it provides a summary and analysis of information regarding the characteristics, toxicity, effects on human health, and current regulations pertaining to PAEs in food. Various approaches for the extraction, purification, and quantification of these analytes are highlighted. Solvent and sorbent-based extraction techniques are reviewed, as are the chromatographic separation and other methods currently applied in the analysis of PAEs in wines and olive oils. The analysis of these contaminants is challenging due to the complexities of the matrices and the widespread presence of PAEs in analytical laboratories, demanding the implementation of appropriate strategies.

Metal concentrations in the whole blood of farmers in southeast Brazil.

In this study, we measured Ni, Co, Cd, and Pb concentrations in the whole blood of farmers from southeast Brazil to address the factors influencing human exposure in this population. The factors included smoking, alcohol consumption, aging, body composition, gender, and feeding preferences, which were measured through carbon and nitrogen isotopic composition. We also calculated and compared the reference values (RVs) of the measured elements to evaluate ongoing exposure levels. We observed the influence of lifestyle habits on metal exposure; Cd levels were statistically higher in smokers, and alcohol consumption affected only Pb concentrations, with an association also observed with the frequency of alcohol ingestion. The metal levels were positively associated with both isotope values, indicating that feeding may be the dominant source of these elements in this population. We also observed the effect of endogenous sources measured through age, as increased Pb concentrations in both genders and higher Cd levels in older women, which is related to bone, kidney, and liver accumulation. The body mass index was negatively associated with Ni, Co, and Cd in women and positively in men. The negative associations may indicate that body fat may act as a reservoir for metals, reducing their availability in the blood in individuals with higher body mass and possibly influencing the assessment of exposure levels. The evaluated population presented elevated RVs for all elements: Ni 36, Co 3.3, Cd 16, and Pb 149 µg L-1. These values point to higher exposure in this population compared to other studies in Brazil and worldwide. These results emphasize an urgent need for monitoring programs for toxic substances in Brazil and evaluating possible health effects, given the ongoing environmental exposure associated with endogenous exposure and lifestyle habits that promote higher metal levels in this population.

Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort study.

Introduction: Despite the existing data on the Multisystem Inflammatory Syndrome in Children (MIS-C), the factors that determine these patients evolution remain elusive. Answers may lie, at least in part, in genetics. It is currently under investigation that MIS-C patients may have an underlying innate error of immunity (IEI), whether of monogenic, digenic, or even oligogenic origin. Methods: To further investigate this hypothesis, 30 patients with MIS-C were submitted to whole exome sequencing. Results: Analyses of genes associated with MIS-C, MIS-A, severe covid-19, and Kawasaki disease identified twenty-nine patients with rare potentially damaging variants (50 variants were identified in 38 different genes), including those previously described in IFNA21 and IFIH1 genes, new variants in genes previously described in MIS-C patients (KMT2D, CFB, and PRF1), and variants in genes newly associated to MIS-C such as APOL1, TNFRSF13B, and G6PD. In addition, gene ontology enrichment pointed to the involvement of thirteen major pathways, including complement system, hematopoiesis, immune system development, and type II interferon signaling, that were not yet reported in MIS-C. Discussion: These data strongly indicate that different gene families may favor MIS- C development. Larger cohort studies with healthy controls and other omics approaches, such as proteomics and RNAseq, will be precious to better understanding the disease dynamics.

Factors associated with acute kidney injury in patients undergoing extracorporeal membrane oxygenation: retrospective cohort.

OBJECTIVE: To identify factors associated with acute kidney injury in patients undergoing extracorporeal membrane oxygenation. METHOD: Retrospective cohort study conducted in an adult Intensive Care Unit with patients undergoing extracorporeal membrane oxygenation from 2012 to 2021. The research used the Kidney Disease Improving Global Outcomes as criteria for definition and classification of acute kidney injury. A multiple logistic regression model was developed to analyze the associated factors. RESULTS: The sample was composed of 122 individuals, of these, 98 developed acute kidney injury (80.3%). In multiple regression, the associated factors found were vasopressin use, Nursing Activities Score, and glomerular filtration rate. CONCLUSION: The use of vasopressin, the Nursing Activities Score, and the glomerular filtration rate were considered as factors related to the development of acute kidney injury in patients undergoing extracorporeal membrane oxygenation.

Methylation of BDNF gene in association with episodic memory in women.

Brain-derived neurotrophic factor (BDNF) gene regulation plays an important role in long-term memory formation, and the DNA methylation (DNAm) level of BDNF promoters has been associated with episodic memory deficits. Our aim was to explore the association between DNAm levels in BDNF promoter IV with verbal learning and memory performance in healthy women. We conducted a cross-sectional study by recruiting 53 individuals. Episodic memory was assessed by using the Rey Auditory Verbal Learning Test (RAVLT). Clinical interviews, RAVLT, and blood sample collection were assessed in all participants. DNAm was measured on DNA from whole peripheral blood using pyrosequencing. According to generalized linear model (GzLM) analyses, cytosine guanine dinucleotide (CpG) site 5 showed significant associations between learning capacity (LC, p < 0.035), that is, every 1% of DNA methylation at CpG site 5 results in a 0.068 reduction in verbal learning performance. To the best of our knowledge, the current study is the first to show that BDNF DNAm plays an important role in episodic memory.

Psychotropic drug use and suggestive depression symptoms associated with NR3C1 DNA methylation / Uso de drogas psicotrópicas e sintomas sugestivos de depressão associados à metilação do DNA do NR3C1

Introduction: Psychiatric disorders have become a global problem that leads millions of people to use psychotropic medications, especially benzodiazepines. The effects of these substances are widely known regarding tolerance and chemical dependence, however, from epigenetics perspective, there are still little known.Objective: To evaluate the association between psychotropic drug use, NR3C1 gene methylation and its relation with symptoms suggestive of depression in adult individuals assisted in the public health system.Methods: 385 adult volunteers (20-59 years) users of the Brazilian Unified Health System were recruited to evaluate socioeconomic, health, lifestyle conditions in a cross sectional study. BDI-II evaluated symptoms suggestive of depression and pyrosequencing evaluated NR3C1 DNA methylation. Bivariate and multivariate Poisson regression model with robust variance (p < 0.05) evaluated the association between psychotropic drug use and NR3C1 gene methylation.Results: Specific depressive symptoms such as irritability, insomnia and fatigability were associated with psychotropic drug use. Symptoms of past failure, indecision and loss of appetite were associated with hypermethylation patterns in CpGs 40 to 47 of NR3C1 gene. Moreover, psychotropic drug use is associated with 50% reduction in NR3C1 gene methylation, through model adjusted with socioeconomic, health and lifestyle confounding variables.Conclusions: Psychotropic drug use and depressive symptoms was associated with changes in NR3C1 DNA methylation. In this context, epigenetic modification resulting from psychotropic drug use and depressive symptoms could be considered, mainly in population studies with epigenetic evaluation, where these factors may be influencing the findings of future studies.

Introdução: os distúrbios psiquiátricos tornaram-se um problema global que leva milhões de pessoas ao uso de medicamentos psicotrópicos. Os efeitos dessas substâncias são amplamente conhecidos quanto à tolerância e dependência química, porém, do ponto de vista epigenético, ainda são pouco conhecidos.Objetivos: avaliar a associação entre o uso de drogas psicotrópicas, metilação do gene NR3C1 e sua relação com sintomas sugestivos de depressão em indivíduos entre 20 a 59 anos usuários da rede pública de saúde.Método: 385 voluntários de 20-59 anos, usuários do Sistema Único de Saúde brasileiro foram recrutados para avaliação das condições socioeconômicas, de saúde e de estilo de vida em estudo transversal. O BDI-II avaliou sintomas sugestivos de depressão e o pirosequenciamento avaliou a metilação do DNA de NR3C1. Modelo de regressão de Poisson bivariado e multivariado com variância robusta (p < 0,05) avaliou a associação entre o uso de drogas psicotrópicas e metilação do gene NR3C1.Resultados: sintomas depressivos específicos como irritabilidade, insônia e fadiga foram associados ao uso de medicamentos psicotrópicos. Sintomas de fracasso passado, indecisão e perda de apetite foram associados a padrões de hipermetilação nos CpGs 40 a 47 do gene NR3C1. Além disso, o uso de psicofármacos está associado à redução de 50% na metilação do gene NR3C1, por meio de modelo ajustado com variáveis de confusão socioeconômicas, de saúde e estilo de vida.Conclusão: o uso de drogas psicotrópicas e sintomas específicos depressivos foram associados a alterações na metilação do DNA de NR3C1.

Partners in academic endeavour: Characterising student engagement across internationally excellent medical schools.

There is increasing interest in how student engagement can be enhanced in medical schools: not just engagement with learning but with broader academic practices such as curriculum development, research, organisational leadership, and community involvement. To foster evidence-based practice, it is important to understand how institutions from diverse sociocultural contexts achieve excellence in student engagement.We analysed 11 successful applications for an international award in student engagement and interviewed nine key informants from five medical schools across four continents, characterising how and why student engagement was fostered at these institutions.Document analysis revealed considerable consensus on the core practices of student engagement, as well as innovative and creative practices often in response to local strengths and challenges. The interviews uncovered the importance of an authentic partnership culture between students and faculty which sustained mutually beneficial enhancements across multiple domains. Faculty promoted, welcomed, and acted on student inputs, and students reported greater willingness to participate if they could see the benefits. These combined to create self-perpetuating virtuous cycles of academic endeavour. Successful strategies included having participatory values actively reinforced by senior leadership, engagement activities that are driven by both students and staff, and focusing on strategies with reciprocal benefits for all stakeholders.

Tobacco use modify exon IV BDNF gene methylation levels in depression.

This study aimed to investigate BDNF gene methylation in individuals with depression based on tobacco use. Therefore, 384 adults from southeastern Brazil were recruited to assess depression, socioeconomic status, lifestyle, and methylation by pyrosequencing exon IV promoter region of the BDNF gene. The Generalized Linear Model (GzLM) was used to check the effect of depression, tobacco, and the interaction between depression and tobacco use in methylation levels. In addition, the Kruskal-Wallis test, followed by Dunn's post hoc test, was used to compare methylation levels. Interaction between depression and tobacco use was significant at levels of BDNF methylation in the CpG 5 (p = 0.045), 8 (p = 0.016), 9 (p = 0.042), 10 (p = 0.026) and mean 5-11 (p < 0.001). Dunn's post hoc test showed that individuals with depression and tobacco use compared to those with or without depression who did not use tobacco had lower levels of BDNF methylation in CpG 5, 6, 7, 8, 9, 11, and mean 5-11. Therefore, we suggest that tobacco use appears to interfere with BDNF gene methylation in depressed individuals.

Factors associated with acute kidney injury in patients undergoing extracorporeal membrane oxygenation: retrospective cohort / Factores asociados a la lesión renal aguda en pacientes sometidos a oxigenación por membrana extracorpórea: cohorte retrospectiva / Fatores associados a lesão renal aguda em pacientes submetidos à oxigenação por membrana extracorpórea: coorte retrospectivo

ABSTRACT Objective: To identify factors associated with acute kidney injury in patients undergoing extracorporeal membrane oxygenation. Method: Retrospective cohort study conducted in an adult Intensive Care Unit with patients undergoing extracorporeal membrane oxygenation from 2012 to 2021. The research used the Kidney Disease Improving Global Outcomes as criteria for definition and classification of acute kidney injury. A multiple logistic regression model was developed to analyze the associated factors. Results: The sample was composed of 122 individuals, of these, 98 developed acute kidney injury (80.3%). In multiple regression, the associated factors found were vasopressin use, Nursing Activities Score, and glomerular filtration rate. Conclusion: The use of vasopressin, the Nursing Activities Score, and the glomerular filtration rate were considered as factors related to the development of acute kidney injury in patients undergoing extracorporeal membrane oxygenation.

RESUMEN Objetivo: Identificar los factores asociados a la lesión renal aguda en pacientes sometidos a oxigenación por membrana extracorpórea. Material y método: Estudio de cohortes retrospectivo realizado en una unidad de cuidados intensivos de adultos con pacientes sometidos a oxigenación por membrana extracorpórea entre 2012 y 2021. El criterio de definición y clasificación de lesión renal aguda fue el Kidney Disease Improving Global Outcomes. Se desarrolló un modelo de regresión logística múltiple para el análisis de los factores asociados. Resultados: La muestra estuvo compuesta por 122 individuos, de estos, 98 desarrollaron lesión renal aguda (80,3%). En la regresión múltiple, los factores asociados encontrados fueron el uso de vasopresina, el Nursing Activities Score y la tasa de filtración glomerular. Conclusión: El uso de vasopresina, el Nursing Activities Score y la tasa de filtración glomerular se consideraron factores relacionados con el desarrollo de lesión renal aguda en pacientes sometidos a oxigenación por membrana extracorpórea.

RESUMO Objetivo: Identificar os fatores associados à lesão renal aguda em pacientes submetidos a oxigenação por membrana extracorpórea. Método: Estudo de coorte retrospectivo, realizado em uma Unidade de Terapia Intensiva adulta, com pacientes submetidos à oxigenação por membrana extracorpórea, no período de 2012 a 2021. O critério para definição e classificação da lesão renal aguda foi o da Kidney Disease Improving Global Outcomes. Para a análise dos fatores associados foi elaborado um modelo de regressão logística múltipla. Resultados: A amostra foi composta por 122 indivíduos, destes, 98 desenvolveram lesão renal aguda (80,3%). Na regressão múltipla, os fatores associados encontrados foram a utilização de vasopressina, o Nursing Activities Score e a taxa de filtração glomerular. Conclusão: O uso da vasopressina, o Nursing Activities Score e a taxa de filtração glomerular foram considerados como fatores relacionados ao desenvolvimento de lesão renal aguda em paciente submetido à oxigenação por membrana extracorpórea.

Methylation of the NR3C1 gene in individual with chronic pain: patient profile in a cross-sectional study with users of the public health system / Metilação do gene NR3C1 em indivíduos com dor crônica: perfil de pacientes em estudo transversal com usuários do sistema público de saúde

ABSTRACT BACKGROUND AND OBJECTIVES: Studies suggest that shared molecular factors can simultaneously affect different chronic pain syndromes. Understanding the epigenetic mechanisms of various diseases that are associated with chronic pain is essential to comprehend its appearance and progression. The objective of this study is to evaluate the association between DNA methylation of the NR3C1 gene with the presence and intensity of chronic pain, as well as predictive factors also considering socioeconomic, health and lifestyle factors correlated with this association, in adult individuals using the Brazilian Unified Health System (Sistema Único de Saúde - SUS) in a municipality in Southeast Brazil. METHODS: This is a cross-sectional study, whose data collection was carried out through interviews to investigate socioeconomic status, lifestyle and health conditions, in addition to anthropometric assessments and blood samples. Data were analyzed by quantitative DNA methylation assays and statistical analysis. CONCLUSION: The findings suggest epigenetic involvement in NR3C1 gene methylation in association with chronic pain and suggest the need to seek new evidence in relation to the mechanisms that explain chronic pain, especially from an epigenetic point of view, as they may provide subsidies for the prevention and control of chronic pain targeting individuals with the profile found in this study.

RESUMO JUSTIFICATIVA E OBJETIVOS: Estudos sugerem que fatores moleculares compartilhados podem afetar simultaneamente diferentes síndromes de dor crônica. Compreender os mecanismos epigenéticos de várias doenças que estão associadas à dor crônica é essencial para entender sua aparência e progressão. O objetivo deste estudo foi avaliar a associação entre metilação do DNA do gene NR3C1, receptor de glicocorticoides, com a presença e intensidade de dor crônica, bem como os fatores preditivos considerando também fatores socioeconômicos, de saúde e de estilo de vida correlacionados com tal associação em pacientes adultos usuários do Sistema Único de Saúde (SUS) em um município do sudeste brasileiro. MÉTODOS: Trata-se de um estudo observacional transversal, cuja coleta de dados foi realizada através de entrevistas para investigação do status socioeconômico, condições de estilo de vida e de saúde, além de avaliações antropométricas e coletas de sangue. Os dados foram analisados por meio de ensaios quantitativos de metilação do DNA e análise estatística. RESULTADOS: Foi observado que 123 participantes (44,1%) apresentaram metilação da região estudada do gene NR3C1. Análises estatísticas univariadas e multivariada mostraram que as variáveis idade e nível de cortisol estão significativamente associadas com a metilação do gene e a presença de dor crônica. CONCLUSÃO: Os achados sugerem envolvimento epigenético na metilação do gene NR3C1 em associação com dor crônica e sugerem a necessidade de se buscar novas evidências em relação aos mecanismos que explicam a dor crônica, sobretudo do ponto de vista epigenético, pois as mesmas poderão trazer subsídios para prevenção e controle da dor crônica visando pacientes com o perfil encontrado nesse estudo.

Lifestyle and NR3C1 exon 1F gene methylation is associated with changes in glucose levels and insulin resistance.

AIMS: the present study aimed to investigate how glucose and insulin levels may be associated with changes in NR3C1 gene methylation levels in adults. MAIN METHODS: 375 volunteers users of the Brazilian Public Unified Health System (SUS) were recruited to assess socioeconomic status, lifestyle, anthropometric data, blood glucose and serum cortisol levels, insulin resistance, and NR3C1 gene methylation assessment. Factors associated with glucose levels and insulin resistance were investigated using multivariate analysis GLzM at 5% significance (p<0.05). KEY FINDINGS: our results verified that glucose levels and insulin resistance were directly related to NR3C1 gene methylation and age, while not being overweight and obese and no tobacco consumption were indirectly related to glucose levels and insulin resistance. SIGNIFICANCE: habits and lifestyle may influence NR3C1 gene regulation, revealing the complexity of environmental impacts on NR3C1 methylation. Furthermore, associated risk factors must be taken into account in epigenetic studies as they directly interfere with blood glucose levels and insulin resistance.

Analysis of breast cancer survival in a northeastern Brazilian state based on prognostic factors: A retrospective cohort study.

Breast cancer is a major health problem worldwide. Analysis of breast cancer epidemiology in emerging countries enables assessment of prognostic factors, cancer care quality, and the equity of resource distribution. We aimed to estimate the overall (OS) and cancer-specific survival (SS) of breast cancer patients in the northeastern Brazilian state of Sergipe to identify independent prognostic factors. We analyzed a cohort for the factors age at diagnosis, place of residence, time to treatment, staging, and molecular classification, using the Kaplan-Meier method, log-rank test, Pearson's chi-squared test and Cox regression model. The outcome was the vital status at the end of the study. Our analysis showed an OS probability of 0.72 and an SS probability of 0.75. In multivariate analysis, time to treatment within 60 days, stage IV, and triple-negative classification remained independent prognostic factors for both OS [unadjusted hazard ratio (HRp) 1.50 (1.21; 1.86), HRp 16.56 (8.35; 32.85), and HRp 2.73 (1.73; 4.29), respectively] and SS [HRp 1.43 (1.13; 1.81), HRp 20.53 (9.45; 44.56), and HRp 3.14 (1.88; 5.26), respectively]. Better survival was demonstrated for the following patients: those receiving their first treatment after 60 days, with an OS of 52.5 months (51.2; 53.8) and SS of 53.5 months (52.3; 54.7); stage I patients, with an OS of 58.8 months (57.7; 60.0) and SS of 59.2 months (58.1; 60.3); patients without nodal metastasis, with an OS of 54.2 months (53.0; 55.4) and SS of 55.6 months (54.5; 56.7); and patients with luminal A classification, with an OS of 56.8 months (55.0; 58.5) and SS of 57.8 months (56.2; 59.4). This study identified independent prognostic factors and that OS and SS were lower for patients from Sergipe than for patients in high-income areas. Therefore, determining the profiles of breast cancer patients in this population will inform specific cancer care.

Transcriptome dynamics during metamorphosis of imaginal discs into wings and thoracic dorsum in Apis mellifera castes.

BACKGROUND: Much of the complex anatomy of a holometabolous insect is built from disc-shaped epithelial structures found inside the larva, i.e., the imaginal discs, which undergo a rapid differentiation during metamorphosis. Imaginal discs-derived structures, like wings, are built through the action of genes under precise regulation. RESULTS: We analyzed 30 honeybee transcriptomes in the search for the gene expression needed for wings and thoracic dorsum construction from the larval wing discs primordia. Analyses were carried out before, during, and after the metamorphic molt and using worker and queen castes. Our RNA-seq libraries revealed 13,202 genes, representing 86.2% of the honeybee annotated genes. Gene Ontology analysis revealed functional terms that were caste-specific or shared by workers and queens. Genes expressed in wing discs and descendant structures showed differential expression profiles dynamics in premetamorphic, metamorphic and postmetamorphic developmental phases, and also between castes. At the metamorphic molt, when ecdysteroids peak, the wing buds of workers showed maximal gene upregulation comparatively to queens, thus underscoring differences in gene expression between castes at the height of the larval-pupal transition. Analysis of small RNA libraries of wing buds allowed us to build miRNA-mRNA interaction networks to predict the regulation of genes expressed during wing discs development. CONCLUSION: Together, these data reveal gene expression dynamics leading to wings and thoracic dorsum formation from the wing discs, besides highlighting caste-specific differences during wing discs metamorphosis.

Recombination mapping of the Brazilian stingless bee Frieseomelitta varia confirms high recombination rates in social hymenoptera.

BACKGROUND: Meiotic recombination is a fundamental genetic process that shuffles allele combinations and promotes accurate segregation of chromosomes. Analyses of the ubiquitous variation of recombination rates within and across species suggest that recombination is evolving adaptively. All studied insects with advanced eusociality have shown exceptionally high recombination rates, which may represent a prominent case of adaptive evolution of recombination. However, our understanding of the relationship between social evolution and recombination rates is incomplete, partly due to lacking empirical data. Here, we present a linkage map of the monandrous, advanced eusocial Brazilian stingless bee, Frieseomelitta varia, providing the first recombination analysis in the diverse Meliponini (Hymenoptera, Apidae). RESULTS: Our linkage map includes 1417 markers in 19 linkage groups. This map spans approximately 2580 centimorgans, and comparisons to the physical genome assembly indicate that it covers more than 75 % of the 275 Megabasepairs (Mbp) F. varia genome. Thus, our study results in a genome-wide recombination rate estimate of 9.3-12.5 centimorgan per Mbp. This value is higher than estimates from nonsocial insects and comparable to other highly social species, although it does not support our prediction that monandry and strong queen-worker caste divergence of F. varia lead to even higher recombination rates than other advanced eusocial species. CONCLUSIONS: Our study expands the association between elevated recombination and sociality in the order Hymenoptera and strengthens the support for the hypothesis that advanced social evolution in hymenopteran insects invariably selects for high genomic recombination rates.

Blood pressure behavior during mechanical thrombectomy and drugs used for conscious sedation or general anesthesia.

BACKGROUND: The optimal blood pressure (BP) during mechanical thrombectomy for acute ischemic stroke is currently unclear. OBJECTIVE: To investigate BP behavior during mechanical thrombectomy in patients with acute ischemic stroke and its relationship with drugs used for sedation or general anesthesia. Additionally, we investigated the association between BP oscillation during mechanical thrombectomy and recanalization status, and with functional outcome at discharge. METHODS: Consecutive patients treated with mechanical thrombectomy for acute ischemic stroke were evaluated in a tertiary hospital from December/2009 to December/2015. Maximum, minimum, and mean systolic and diastolic BP, and mean arterial pressures were collected during the procedure. Sedative drugs were also reviewed. RESULTS: Fifty-three patients with a mean age of 71.9 years (60.4% men) were treated with mechanical thrombectomy. The mean reduction in systolic BP and mean arterial pressure from hospital admission to mechanical thrombectomy were respectively 42 and 36 mmHg. During the procedure, oscillations were 50.4 mmHg for systolic, and 33.2 mmHg for diastolic BP. Patients treated with neuromuscular blocking drugs had more oscillation in systolic BP from hospital admission to procedure (51.1 versus 26.2 mmHg, P=0.06). The use of cisatracurium (43.9 versus 29.6 mmHg, P=0.02) and succinylcholine (44.7 versus 29.3 mmHg, P=0.01) were associated with a significant drop in BP during the procedure. CONCLUSIONS: Significant BP oscillation occurs during mechanical thrombectomy. Drugs used for conscious sedation or general anesthesia, specifically neuromuscular blocking agents, might have an influence upon BP levels.

Genomic analysis of Burkholderia cenocepacia isolated from a liver abscess in a patient with cystic fibrosis.

Burkholderia cenocepacia complex is associated with high transmissibility, virulence, and poor prognosis in cystic fibrosis (CF) patients. However, extrapulmonary infections are rare. We investigated the genome of a B. cenocepacia IIIA isolated from a liver abscess in a Brazilian CF patient and compared it to strain J2315. The whole genome was sequenced, and contigs were annotated by Rapid Annotation using Subsystem Technology. The Pathosystems Resource Integration Center was used to map antimicrobial and virulence genes. The genomic island (GIs) analysis was performed using two prediction methods, and the presence of putative plasmids and insertion sequences (ISs) was investigated. The isolate was confirmed as B. cenocepacia IIIA to ST-28 (ET12 lineage). A total of 64 genes for antimicrobial resistance and 47 genes related to virulence were identified. Among the virulence factors, there was a predominance of factors related to the invasion mechanism, to the flagellar biosynthesis protein, and to the RNA polymerase sigma factor for flagellar operon (cdpA). Two IS families (IS3 and IS5) and only one plasmid were found. On average 56 GIs were predicted by at least one of the methods applied. Comparative analysis showed resistance mechanisms and virulence factors revealing invasive determinants used by B. cenocepacia IIIA (ET12) in the process of disease spread to other infection sites (extrapulmonary) of highly virulent strains in CF patients.

Blood pressure behavior during mechanical thrombectomy and drugs used for conscious sedation or general anesthesia / Comportamento da pressão arterial durante trombectomia mecânica e drogas utilizadas para sedação consciente ou anestesia geral

ABSTRACT Background: The optimal blood pressure (BP) during mechanical thrombectomy for acute ischemic stroke is currently unclear. Objective: To investigate BP behavior during mechanical thrombectomy in patients with acute ischemic stroke and its relationship with drugs used for sedation or general anesthesia. Additionally, we investigated the association between BP oscillation during mechanical thrombectomy and recanalization status, and with functional outcome at discharge. Methods: Consecutive patients treated with mechanical thrombectomy for acute ischemic stroke were evaluated in a tertiary hospital from December/2009 to December/2015. Maximum, minimum, and mean systolic and diastolic BP, and mean arterial pressures were collected during the procedure. Sedative drugs were also reviewed. Results: Fifty-three patients with a mean age of 71.9 years (60.4% men) were treated with mechanical thrombectomy. The mean reduction in systolic BP and mean arterial pressure from hospital admission to mechanical thrombectomy were respectively 42 and 36 mmHg. During the procedure, oscillations were 50.4 mmHg for systolic, and 33.2 mmHg for diastolic BP. Patients treated with neuromuscular blocking drugs had more oscillation in systolic BP from hospital admission to procedure (51.1 versus 26.2 mmHg, P=0.06). The use of cisatracurium (43.9 versus 29.6 mmHg, P=0.02) and succinylcholine (44.7 versus 29.3 mmHg, P=0.01) were associated with a significant drop in BP during the procedure. Conclusions: Significant BP oscillation occurs during mechanical thrombectomy. Drugs used for conscious sedation or general anesthesia, specifically neuromuscular blocking agents, might have an influence upon BP levels.

RESUMO Antecedentes: Atualmente, a pressão arterial ideal durante a trombectomia mecânica em pacientes com acidente vascular cerebral isquêmico agudo não é clara. Objetivo: Investigar o comportamento da pressão arterial durante a trombectomia mecânica em pacientes com acidente vascular cerebral isquêmico agudo e sua relação com os medicamentos utilizados para sedação ou anestesia geral. Adicionalmente, investigar a associação entre a oscilação da pressão arterial durante a trombectomia mecânica e a capacidade de recanalização, além do status funcional no momento da alta hospitalar. Métodos: Avaliação de pacientes tratados com trombectomia mecânica por acidente vascular cerebral isquêmico agudo em um hospital terciário de dezembro/2009 a dezembro/2015. Valores máximos, mínimos e médios da pressão arterial sistólica, pressão diastólica e pressão arterial média foram coletados durante o procedimento. Drogas sedativas utilizadas também foram revisadas. Resultados: Um total de 53 pacientes com idade média de 71,9 anos (60,4% homens) foram tratados com trombectomia mecânica. A redução média da pressão arterial sistólica e da pressão arterial média desde a internação até a trombectomia mecânica foi respectivamente de 42 mmHg e 36 mmHg. Durante o procedimento, as oscilações da pressão arterial foram de 50,4 mmHg para pressão sistólica e 33,2 mmHg para pressão diastólica. Os pacientes tratados com bloqueadores neuromusculares apresentaram uma tendência a maior oscilação da pressão arterial sistólica desde a internação até o procedimento (51,1 mmHg versus 26,2 mmHg, P = 0,06). O uso de cisatracúrio (43,9 mmHg versus 29,6 mmHg, P = 0,02) e succinilcolina (44,7 mmHg versus 29,3 mmHg, P = 0,01) foram associados a uma queda significativa da pressão arterial durante o procedimento. Conclusões: Durante a trombectomia mecânica ocorre oscilação significativa da pressão arterial. Os medicamentos usados para sedação consciente ou anestesia geral, especificamente bloqueadores neuromusculares, podem ter influência nos níveis de pressão arterial.

Proteogenomics Reveals Orthologous Alternatively Spliced Proteoforms in the Same Human and Mouse Brain Regions with Differential Abundance in an Alzheimer's Disease Mouse Model.

Alternative splicing (AS) may increase the number of proteoforms produced by a gene. Alzheimer's disease (AD) is a neurodegenerative disease with well-characterized AS proteoforms. In this study, we used a proteogenomics strategy to build a customized protein sequence database and identify orthologous AS proteoforms between humans and mice on publicly available shotgun proteomics (MS/MS) data of the corpus callosum (CC) and olfactory bulb (OB). Identical proteotypic peptides of six orthologous AS proteoforms were found in both species: PKM1 (gene PKM/Pkm), STXBP1a (gene STXBP1/Stxbp1), Isoform 3 (gene HNRNPK/Hnrnpk), LCRMP-1 (gene CRMP1/Crmp1), SP3 (gene CADM1/Cadm1), and PKCßII (gene PRKCB/Prkcb). These AS variants were also detected at the transcript level by publicly available RNA-Seq data and experimentally validated by RT-qPCR. Additionally, PKM1 and STXBP1a were detected at higher abundances in a publicly available MS/MS dataset of the AD mouse model APP/PS1 than its wild type. These data corroborate other reports, which suggest that PKM1 and STXBP1a AS proteoforms might play a role in amyloid-like aggregate formation. To the best of our knowledge, this report is the first to describe PKM1 and STXBP1a overexpression in the OB of an AD mouse model. We hope that our strategy may be of use in future human neurodegenerative studies using mouse models.