Identification and characterization of expressed retrotransposons in the genome of the Paracoccidioides species complex

Background: Species from the Paracoccidioides complex are thermally dimorphic fungi and the causative agents of paracoccidioidomycosis, a deep fungal infection that is the most prevalent systemic mycosis in Latin America and represents the most important cause of death in immunocompetent individuals with systemic mycosis in Brazil. We previously described the identification of eight new families of DNA transposons in Paracoccidioides genomes. in this work, we aimed to identify potentially active retrotransposons in Paracoccidioides genomes.Results: We identified five different retrotransposon families (four LTR-like and one LINE-like element) in the genomes of three Paracoccidioides isolates. Retrotransposons were present in all of the genomes analyzed. P. brasiliensis and P. lutzii species harbored the same retrotransposon lineages but differed in their copy numbers. in the Pb01, Pb03 and Pb18 genomes, the number of LTR retrotransposons was higher than the number of LINE-like elements, and the LINE-like element RtPc5 was transcribed in Paracoccidioides lutzii (Pb01) but could not be detected in P. brasiliensis (Pb03 and Pb18) by semi-quantitative RT-PCR.Conclusion: Five new potentially active retrotransposons have been identified in the genomic assemblies of the Paracoccidioides species complex using a combined computational and experimental approach. the distribution across the two known species, P. brasiliensis and P. lutzii, and phylogenetics analysis indicate that these elements could have been acquired before speciation occurred. the presence of active retrotransposons in the genome may have implications regarding the evolution and genetic diversification of the Paracoccidioides genus.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, BR-31270901 Belo Horizonte, MG, BrazilUniv Fed Minas Gerais, Inst Ciencias Biol, Programa Posgrad Bioinformat, BR-31270901 Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, SP, BrazilUniv Brasilia, Inst Ciencias Biol, Lab Biol Mol, BR-70910900 Brasilia, DF, BrazilUniv Fed Goias, Inst Ciencias Biol, Lab Biol Mol, BR-74001970 Goiania, Go, BrazilFIOCRUZ Minas, Ctr Pesquisas Rene Rachou, Grp Informat Biossistemas, BR-30190002 Belo Horizonte, MG, BrazilUniv Fed Minas Gerais, Dept Biol Geral, BR-31270901 Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, SP, BrazilFAPEMIG: APQ-01661-13CNPq: 301652/2012-0CNPq: 486618/2013-7Web of Scienc

A percepção de justiça organizacional distributiva diante de ações que oferecem recursos e oportunidades à diversidade

This study aimed to investigate whether the organizational actions that offer resources for diversity (women in general, black people and people with disabilities) are perceived as fair. The theoretical framework used was based on the theory Multiprincípio Miller (1976). This theory holds that the distribution of resources can be considered fair not only based on the principle of equity / meritocracy, but also on the principles of equality which aims at a common destination for individuals and the principle of necessity which sees the distribution of resources as fair for one who has difficulties in satisfying your needs for yourself. To this end, it was conducted an exploratory study on the quantitative method. Data were obtained from a scale developed for this study. The sample consisted of 253 persons (52% women, 84% Caucasian and 94% without disabilities). Data analysis was based on the descriptive statistics and inferential. The results indicated that the actions under study are predominantly perceived as fair when based on the principle of equity, but there are differences of perception, considering the gender, race and whether or not people with disabilities, thus revealing important contributions for gender studies in organizational environment.RESUMOEste estudo objetivou investigar se as ações organizacionais que oferecem recursos em prol da diversidade (mulheres em geral, pessoas negras e pessoas com deficiência) são percebidas como justas. O referencial teórico utilizado baseou-se na Teoria do Multiprincípio de Miller (1976). Essa teoria defende que a oferta de recursos pode ser considerada justa não somente a partir do princípio da equidade/meritocracia, mas também, a partir dos princípios da igualdade que almeja um destino comum para os indivíduos e do princípio da necessidade que concebe a distribuição de recursos como justa para aquele que possui dificuldade de satisfazer por si só as suas necessidades. Para tanto, foi realizada uma pesquisa exploratória sob o método quantitativo. Os dados foram obtidos de uma escala desenvolvida para esse estudo. A amostra foi de 253 pessoas (52% mulheres, 84% de raça branca e 94% sem deficiência). A análise dos dados baseou-se na estatística descritiva e na inferencial. Os resultados indicaram que as ações em estudo são predominantemente percebidas como justas quando embasadas no princípio da equidade, mas que há diferenças de percepção considerando-se as variáveis: sexo, raça e ser ou não pessoa com deficiência, revelando assim, contribuições relevantes para os estudos de gênero no ambiente organizacional

Qualidade de vida de pacientes com deformidades dentofaciais submetidos a cirurgia ortognática / Quality of life of patients with dentofacial deformities submitted to orthognatic surgery

A cirurgia ortognática tem tido demanda crescente. Deformidades faciais e problemas esqueléticos causam distúrbios às funções fisiológicas e levam muitos pacientes a buscar tal tratamento, que acarreta mudanças importantes na qualidade de vida. Este estudo observacional longitudinal mensurou o tamanho do efeito, e comparou a qualidade de vida antes e após a cirurgia ortognática com relação aos seguintes fatores: sexo, idade, renda, escolaridade, queixa principal, tipo de deformidade, tipo de cirurgia e grau de satisfação com o aspecto facial pós-operatório. Foram aplicados um formulário de identificação e sócio-demográfico e o Brazilian Orthognathic Quality of Life Questionnaire a 17 pacientes atendidos em um consultório odontológico particular, uma semana antes e 6 semanas após a cirurgia. A amostra foi calculada através da prevalência de impacto. Foi realizada análise descritiva através do software GraphPad Prism (GraphPad Software) e o teste de Correlação de Sperman aplicado em nível de significância de 0,01. A maior parte (76,47%) se declarou muito satisfeita com o resultado do procedimento. O tamanho do efeito calculado com o escore total do questionário foi de 1,57. Foram encontradas correlações significativas no pré-operatório entre o domínio social e a satisfação com a estética facial e entre conscientização da deformidade e tipo de deformidade; no pós-operatório, entre o domínio estética facial e o tipo de deformidade e entre a função oral e o sexo e satisfação com a aparência facial. A cirurgia ortognática tem impacto positivo especialmente sobre a satisfação com a aparência facial, podendo estar condicionado ao grau de escolaridade

Diretriz Brasileira sobre a Saúde Cardiovascular no Climatério e na Menopausa – 2024

Women, who represent approximately half of the global population according to estimates as of January 2024, may experience signs and symptoms of menopause for at least one-third of their lives, during which they have a higher risk of cardiovascular morbidity and mortality. The effects of menopausal hormone therapy (MHT) on the progression of atherosclerosis and cardiovascular disease (CVD) events vary depending on the age at which MHT is initiated and the time since menopause until its initiation. Beneficial effects on CVD outcomes and all-cause mortality have been observed when MHT was initiated before the age of 60 or within 10 years after menopause. The decision regarding the initiation, dose, regimen, and duration of MHT should be made individually after discussing the benefits and risks with each patient. For primary prevention of postmenopausal chronic conditions, the combined use of estrogen and progestogen is not recommended in asymptomatic women, nor is the use of estrogen alone in hysterectomized women. Hormone-dependent neoplasms contraindicate MHT. For the treatment of genitourinary syndrome of menopause, vaginal estrogen therapy may be used in patients with known cardiovascular risk factors or established CVD. For women with contraindications to MHT or who refuse it, non-hormonal therapies with proven efficacy (antidepressants, gabapentin, and fezolinetant) may improve vasomotor symptoms. Compounded hormonal implants, or "bioidentical" and "compounded" hormones, and "hormone modulation" are not recommended due to lack of scientific evidence of their effectiveness and safety.Mujeres, que representan aproximadamente la mitad de la población mundial según estimaciones de enero de 2024, pueden experimentar signos y síntomas de la menopausia durante al menos un tercio de sus vidas, durante los cuales tienen un mayor riesgo de morbilidad y mortalidad cardiovascular. Los efectos de la terapia hormonal de la menopausia (THM) en la progresión de la aterosclerosis y los eventos de enfermedad cardiovascular (ECV) varían según la edad en que se inicia la THM y el tiempo transcurrido desde la menopausia hasta su inicio. Se han observado efectos beneficiosos en los resultados de ECV y la mortalidad por todas las causas cuando la THM se inició antes de los 60 años o dentro de los 10 años posteriores a la menopausia. La decisión sobre la iniciación, dosis, régimen y duración de la THM debe tomarse individualmente después de discutir los beneficios y riesgos con cada paciente. Para la prevención primaria de condiciones crónicas en la posmenopausia, no se recomienda el uso combinado de estrógeno y progestágeno en mujeres asintomáticas, ni el uso de estrógeno solo en mujeres histerectomizadas. Las neoplasias dependientes de hormonas contraindican la THM. Para el tratamiento del síndrome genitourinario de la menopausia, se puede usar terapia estrogénica vaginal en pacientes con factores de riesgo cardiovascular conocidos o ECV establecida. Para mujeres con contraindicaciones a la THM o que la rechazan, las terapias no hormonales con eficacia demostrada (antidepresivos, gabapentina y fezolinetant) pueden mejorar los síntomas vasomotores. Los implantes hormonales compuestos, o hormonas "bioidénticas" y "compuestas", y la "modulación hormonal" no se recomiendan debido a la falta de evidencia científica sobre su efectividad y seguridad.As mulheres, que representam cerca de metade da população mundial segundo estimativas de janeiro de 2024, podem sofrer com sinais e sintomas da menopausa durante pelo menos um terço de suas vidas, quando apresentam maiores risco e morbimortalidade cardiovasculares. Os efeitos da terapia hormonal da menopausa (THM) na progressão de eventos de aterosclerose e doença cardiovascular (DCV) variam de acordo com a idade em que a THM é iniciada e o tempo desde a menopausa até esse início. Efeitos benéficos nos resultados de DCV e na mortalidade por todas as causas ocorreram quando a THM foi iniciada antes dos 60 anos de idade ou nos 10 anos que se seguiram à menopausa. A decisão sobre o início, a dose, o regime e a duração da THM deve ser tomada individualmente após discussão sobre benefícios e riscos com cada paciente. Para a prevenção primária de condições crônicas na pós-menopausa, não se recomendam o uso combinado de estrogênio e progestagênio em mulheres assintomáticas nem o uso de estrogênio sozinho em mulheres histerectomizadas. Neoplasias hormônio-dependentes contraindicam a THM. Para tratamento da síndrome geniturinária da menopausa, pode-se utilizar terapia estrogênica por via vaginal em pacientes com fatores de risco cardiovascular conhecidos ou DCV estabelecida. Para mulheres com contraindicação à THM ou que a recusam, terapias não hormonais com eficácia comprovada (antidepressivos, gabapentina e fezolinetante) podem melhorar os sintomas vasomotores. Os implantes hormonais manipulados, ou hormônios “bioidênticos” “manipulados”, e a ‘modulação hormonal’ não são recomendados pela falta de evidência científica de sua eficácia e segurança

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Análise do impacto de dados incompletos na obtenção de mapas de contorno, a partir de variáveis epidemiológicas

Texto en portugúesTesis, Universidade Federal do Rio de Janeiro, 199

A massive human co-expression-network and its medical applications

Network-based analysis is indispensable in analyzing high throughput biological data. Based on the assumption that the variation of gene interactions under given biological conditions could be better interpreted in the context of a large-scale and wide variety of developmental, tissue, and disease, we leverage the large quantity of publicly-available transcriptomic data > 40,000 HG U133A Affymetrix microarray chips stored in ArrayExpress (http://www.ebi.ac.uk/arrayexpress/) using MetaOmGraph (http://metnet.vrac.iastate.edu/MetNet_MetaOmGraph.htm). From this data, 18,637 chips encompassing over 500 experiments containing high quality data (18637Hu-dataset) were used to create a globally stable gene co-expression network (18637Hu-co-expressionnetwork). Regulons, groups of highly and consistently co-expressed genes, were obtained by partitioning the 18637Hu-co-expression-network using an MCL clustering algorithm. The regulon were demonstrated to be statistically significant using a gene ontology (GO) term overrepresentation test combined with evaluation of the effects of gene permutations. The regulons include approximately 12% of human genes, interconnected by 31,471 correlations. All network data and metadata is publically available (http://metnet.vrac.iastate.edu/ MetNet_MetaOmGraph.htm). Text mining of these metadata, GO term overrepresentation analysis, and statistical analysis of transcriptomic experiments across multiple environmental, tissue, and disease conditions, has revealed novel fingerprints distinguishing central nervous system (CNS)-related conditions. This study demonstrates the value of mega-scale network-based analysis for biologists to further refine transcriptomic data derived from a particular condition, to study the global relationships between genes and diseases, and to develop hypotheses that can inform future research.This is the peer reviewed version of the following article: Feng, Y., Hurst, J., Almeida-De-Macedo, M., Chen, X., Li, L., Ransom, N. and Wurtele, E. S. (2012), Massive Human Co-Expression Network and Its Medical Applications. Chemistry & Biodiversity, 9: 868–887, which has been published in final form at doi:10.1002/cbdv.201100355. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.</p