A Machine Learning Approach for Identifying Novel Cell Type–Specific Transcriptional Regulators of Myogenesis

Transcriptional enhancers integrate the contributions of multiple classes of transcription factors (TFs) to orchestrate the myriad spatio-temporal gene expression programs that occur during development. A molecular understanding of enhancers with similar activities requires the identification of both their unique and their shared sequence features. To address this problem, we combined phylogenetic profiling with a DNA–based enhancer sequence classifier that analyzes the TF binding sites (TFBSs) governing the transcription of a co-expressed gene set. We first assembled a small number of enhancers that are active in Drosophila melanogaster muscle founder cells (FCs) and other mesodermal cell types. Using phylogenetic profiling, we increased the number of enhancers by incorporating orthologous but divergent sequences from other Drosophila species. Functional assays revealed that the diverged enhancer orthologs were active in largely similar patterns as their D. melanogaster counterparts, although there was extensive evolutionary shuffling of known TFBSs. We then built and trained a classifier using this enhancer set and identified additional related enhancers based on the presence or absence of known and putative TFBSs. Predicted FC enhancers were over-represented in proximity to known FC genes; and many of the TFBSs learned by the classifier were found to be critical for enhancer activity, including POU homeodomain, Myb, Ets, Forkhead, and T-box motifs. Empirical testing also revealed that the T-box TF encoded by org-1 is a previously uncharacterized regulator of muscle cell identity. Finally, we found extensive diversity in the composition of TFBSs within known FC enhancers, suggesting that motif combinatorics plays an essential role in the cellular specificity exhibited by such enhancers. In summary, machine learning combined with evolutionary sequence analysis is useful for recognizing novel TFBSs and for facilitating the identification of cognate TFs that coordinate cell type–specific developmental gene expression patterns

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Rediscovering the value of families for psychiatric genetics research

As it is likely that both common and rare genetic variation are important for complex disease risk, studies that examine the full range of the allelic frequency distribution should be utilized to dissect the genetic influences on mental illness. The rate limiting factor for inferring an association between a variant and a phenotype is inevitably the total number of copies of the minor allele captured in the studied sample. For rare variation, with minor allele frequencies of 0.5% or less, very large samples of unrelated individuals are necessary to unambiguously associate a locus with an illness. Unfortunately, such large samples are often cost prohibitive. However, by using alternative analytic strategies and studying related individuals, particularly those from large multiplex families, it is possible to reduce the required sample size while maintaining statistical power. We contend that using whole genome sequence (WGS) in extended pedigrees provides a cost-effective strategy for psychiatric gene mapping that complements common variant approaches and WGS in unrelated individuals. This was our impetus for forming the “Pedigree-Based Whole Genome Sequencing of Affective and Psychotic Disorders” consortium. In this review, we provide a rationale for the use of WGS with pedigrees in modern psychiatric genetics research. We begin with a focused review of the current literature, followed by a short history of family-based research in psychiatry. Next, we describe several advantages of pedigrees for WGS research, including power estimates, methods for studying the environment, and endophenotypes. We conclude with a brief description of our consortium and its goals.This research was supported by National Institute of Mental Health grants U01 MH105630 (DCG), U01 MH105634 (REG), U01 MH105632 (JB), R01 MH078143 (DCG), R01 MH083824 (DCG & JB), R01 MH078111 (JB), R01 MH061622 (LA), R01 MH042191 (REG), and R01 MH063480 (VLN).UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Biología Celular y Molecular (CIBCM)UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biologí

Atenção domiciliar como mudança do modelo tecnoassistencial Atención domiciliar como cambio del modelo tecnoasistencial Home care as change of the technical-assistance model

OBJETIVO: Analisar práticas de atenção domiciliar de serviços ambulatoriais e hospitalares e sua constituição como rede substitutiva de cuidado em saúde. PROCEDIMENTOS METODOLÓGICOS: Estudo qualitativo que analisou, com base na metodologia de caso traçador, quatro serviços ambulatoriais de atenção domiciliar da Secretaria Municipal de Saúde e um serviço de um hospital filantrópico do município de Belo Horizonte, MG, entre 2005 e 2007. Foram realizadas entrevistas com gestores e equipes dos serviços de atenção domiciliar, análise de documentos e acompanhamento de casos com entrevistas a pacientes e cuidadores. A análise foi orientada pelas categorias analíticas integração da atenção domiciliar na rede de saúde e modelo tecnoassistencial. ANÁLISE DOS RESULTADOS: A implantação da atenção domiciliar foi precedida por decisão político-institucional tanto com orientação racionalizadora, buscando a diminuição de custos, quanto com vistas à reordenação tecnoassistencial das redes de cuidados. Essas duas orientações encontram-se em disputa e constituem dificuldades para conciliação dos interesses dos diversos atores envolvidos na rede e na criação de espaços compartilhados de gestão. Pôde-se identificar a inovação tecnológica e a autonomia das famílias na implementação dos projetos de cuidado. As equipes mostraram-se coesas, construindo no cotidiano do trabalho novas formas de integrar os diferentes olhares para transformação das práticas em saúde. Foram observados desafios na proposta de integrar os diferentes serviços de caráter substitutivo do cuidado ao limitar a capacidade da atenção domiciliar de mudar o modelo tecnoassistencial. CONCLUSÕES: A atenção domiciliar possui potencial para constituição de uma rede substitutiva ao produzir novos modos de cuidar que atravessam os projetos dos usuários, dos familiares, da rede social e dos trabalhadores da atenção domiciliar. A atenção domiciliar como modalidade substitutiva de atenção à saúde requer sustentabilidade política, conceitual e operacional, bem como reconhecimento dos novos arranjos e articulação das propostas em curso.<br>OBJETIVO: Analizar prácticas de atención domiciliar de servicios de ambulatorio y hospitalarios y su constitución como red sustitutiva de cuidado en salud. PROCEDIMIENTOS METODOLÓGICOS: Estudio cualitativo que analizó, con base en la metodología de caso trazador, cuatro servicios de ambulatorio e atención domiciliar de la Secretaria Municipal de Salud y un servicio de un hospital filantrópico del municipio de Belo Horizonte, Sureste de Brasil, entre 2005 y 2007. Fueron realizadas entrevistas con gestores y equipos de los servicios de atención domiciliar, análisis de documentos y acompañamiento de casos con entrevistas a pacientes y cuidadores. El análisis fue orientado por las categorías analíticas integración de la atención domiciliar en la red de salud y modelo tecnoasistencial. ANÁLISIS DE LOS RESULTADOS: La implantación de la atención domiciliar fue precedida por decisión político-institucional tanto con orientación racionalizadota, buscando disminución de costos, como con miras a la reordenación tecnoasistencial de las redes de cuidados. Esas dos orientaciones se encuentran en disputa y constituyen dificultades para conciliación de los intereses de los diversos actores envueltos en la red y en la creación de espacios compartidos de gestión. Se puede identificar la innovación tecnológica y la autonomía de las familias en la implementación de los proyectos de cuidado. Los equipos se mostraron unidos, construyendo en el cotidiano del trabajo nuevas formas de integrar las diferentes visiones para transformación de las prácticas en salud. Fueron observados desafíos en la propuesta de integrar los diferentes servicios de carácter sustitutivo del cuidado al limitar la capacidad de atención domiciliar si se muda el modelo tecnoasistencial. CONCLUSIONES: La atención domiciliar posee potencial para constitución de una red sustitutiva al producir nuevos modos de cuidar que atraviesan los proyectos de los usuarios, de los familiares, de la red social y de los trabajadores de la atención domiciliar. La atención domiciliar como modalidad sustitutiva de atención a la salud requiere sustentabilidad política, conceptual y operacional, así como reconocimiento de los nuevos arreglos y articulación de las propuestas en curso.<br>OBJECTIVE: To analyze home care practices of outpatient and hospital services and their constitution as a substitute healthcare network. METHODOLOGICAL PROCEDURES: A qualitative study was carried out using tracer methodology to analyze four outpatient home care services from the Municipal Health Department and one service from a philanthropic hospital in the municipality of Belo Horizonte, Southeastern Brazil, between 2005 and 2007. The following procedures were carried out: interviews with the home care services' managers and teams, analysis of documents and follow-up of cases, holding interviews with patients and caregivers. The analysis was guided by the analytical categories home care integration into the healthcare network and technical-assistance model. RESULTS: Home care implementation was preceded by a political-institutional decision, both with a rationalizing orientation, intending to promote cost reduction, and also with the aim of carrying out the technical-assistance rearrangement of the healthcare networks. These two types of orientation were found to be in conflict, which implies difficulties for conciliating interests of the different players involved in the network, and also the creation of shared management spaces. It was possible to identify technological innovation and families' autonomy in the implementation of the healthcare projects. The teams proved to be cohesive, constructing, in the daily routine, new forms of integrating different perspectives so as to transform the healthcare practices. Challenges were observed in the proposal of integrating the different substitutive healthcare services, as the home care services' capacity to change the technical-assistance model is limited. CONCLUSIONS: Home care has potential for constituting a substitutive network by producing new care modalities that cross the projects of users, family members, social network, and home care professionals. Home care as a substitute healthcare modality requires political, conceptual and operational sustainability, as well as recognition of the new arrangements and articulation of ongoing proposals

Work ability and stress in a bus transportation company in Belo Horizonte, Brazil Avaliação da capacidade para o trabalho e estresse em uma empresa de transporte coletivo de Belo Horizonte, Brasil

Demographic, occupational and psychosocial characteristics affect the health and occupational performance of workers. The objective of the present study was to elaborate a profile of the work ability and factors that affect it in a bus transportation company in Belo Horizonte, Brazil. The instruments used included a socio-demographic and occupational questionnaire, the Work Ability Index and the Job Stress Scale. Demographic information revealed that 85.7% of the 126 employees of the company were active workers, 98% were males, with an average of 39 years of age (SD= 10) and 79 months working in the company (SD= 68); more than half reported having a low schooling level. In terms of personal habits, 88% were exposed to one or more risk factors, especially a sedentary lifestyle. The average strain value (as a consequence of stress) was 0.78 (SD= 0.2) and 75.3% reported episodes of violence at the workplace. The work ability was good to excellent among 89% of the workers. Results from the logistic regression analysis showed that strain was the only significant variable in relation to the Work Ability Index, (estimated odds ratio of 0.02). The results suggest that psychosocial factors presented the greatest association with work ability, and preventive and/or corrective measures should be implemented.<br>Características demográficas, ocupacionais e psicossociais afetam a saúde e o desempenho dos trabalhadores. O objetivo deste estudo foi elaborar um perfil da capacidade para o trabalho e fatores que a afetam em uma empresa de transporte coletivo de Belo Horizonte, Brasil. Os instrumentos utilizados foram o Índice de Capacidade para o Trabalho, a Job Stress Scale e um questionário sociodemográfico e ocupacional. Dos 126 trabalhadores, 14,3% estavam aposentados ou afastados, todos por doença. Entre os ativos, a maioria era do sexo masculino (98%), com idade média de 39 anos (DP=10), baixa escolaridade (acima de 50%) e tempo médio na empresa de 79 meses (DP=68). Quanto aos hábitos pessoais, 88% estavam expostos a um ou mais fatores de risco, em especial o sedentarismo. O valor médio de desgaste (conseqüência do estresse) foi 0,78 (DP=0.2) e 75,3% relataram episódios de violência no trabalho. A capacidade para o trabalho foi boa ou ótima em 89% dos casos. No modelo de regressão logística com variável resposta ICT, a única variável significativa foi o desgaste (razão de chance estimada de 0,02). Os resultados sugerem que fatores psicossociais apresentaram maior associação com a capacidade para o trabalho e medidas preventivas e/ou corretivas devem ser implementadas