RESUMO
BACKGROUND: Complicated intra-abdominal infections (cIAIs) are associated with significant morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with cIAI in a multicentre study and to develop clinical prediction models (CPMs) to help identify patients at risk of mortality or relapse. METHODS: A multicentre observational study was conducted from August 2016 to February 2017 in the UK. Adult patients diagnosed with cIAI were included. Multivariable logistic regression was performed to develop CPMs for mortality and cIAI relapse. The c-statistic was used to test model discrimination. Model calibration was tested using calibration slopes and calibration in the large (CITL). The CPMs were then presented as point scoring systems and validated further. RESULTS: Overall, 417 patients from 31 surgical centres were included in the analysis. At 90 days after diagnosis, 17.3 per cent had a cIAI relapse and the mortality rate was 11.3 per cent. Predictors in the mortality model were age, cIAI aetiology, presence of a perforated viscus and source control procedure. Predictors of cIAI relapse included the presence of collections, outcome of initial management, and duration of antibiotic treatment. The c-statistic adjusted for model optimism was 0.79 (95 per cent c.i. 0.75 to 0.87) and 0.74 (0.73 to 0.85) for mortality and cIAI relapse CPMs. Adjusted calibration slopes were 0.88 (95 per cent c.i. 0.76 to 0.90) for the mortality model and 0.91 (0.88 to 0.94) for the relapse model; CITL was -0.19 (95 per cent c.i. -0.39 to -0.12) and - 0.01 (- 0.17 to -0.03) respectively. CONCLUSION: Relapse of infection and death after complicated intra-abdominal infections are common. Clinical prediction models were developed to identify patients at increased risk of relapse or death after treatment, these now require external validation.
Assuntos
Regras de Decisão Clínica , Infecções Intra-Abdominais/etiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Feminino , Humanos , Infecções Intra-Abdominais/diagnóstico , Infecções Intra-Abdominais/tratamento farmacológico , Infecções Intra-Abdominais/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Recidiva , Fatores de RiscoRESUMO
Reprogramming of somatic cells is associated with overcoming the established epigenetic barrier. Key events in this process are changes in the DNA methylation landscape and histone modifications. Studying the factors affecting epigenetic plasticity will allow not only to reveal the principles underlying cell reprogramming but also to find possible ways to influence this process. Kaiso transcription factor is one of the protein interpreters of methylated DNA. By binding to methylated DNA, Kaiso attracts corepressor complexes affecting chromatin structure. In this work, we showed that the Kaiso gene knockout contributes to more efficient somatic reprogramming by affecting both cell proliferation and DNA methylation. The proposed mechanisms for the increase in the efficiency of somatic reprogramming associated with the Kaiso gene knockout is a decrease in the methylation level of the Oct4 promoter region in mouse embryonic fibroblasts before reprogramming.
Assuntos
Reprogramação Celular , Técnicas de Inativação de Genes , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fatores de Transcrição/metabolismoRESUMO
A histometric analysis of the alterations at the motor end plate in dystrophic Bar Harbor mice has been performed. In both forms of mouse dystrophy, simplification and focal atrophy of the junctional folds and retraction of the nerve terminal represented the significant changes. The postsynaptic alterations were similar to those described in Duchenne dystrophy. In constrast, the presence of presynaptic alterations in these mice indicated the presence of both a neural and a muscular abnormality. The wedge-shaped focal lesions in the muscle of dystrophic mice were demonstrated by both in vitro and in vivo HRP tracer techniques. These focal degenerative changes in muscle were similar to those described in Duchenne dystrophy. Employing the technique of extracellular space tracing, a comparison was made of the appearance of the transverse tubular system in the various types of dystrophic muscle fibers.
Assuntos
Placa Motora/ultraestrutura , Músculos/patologia , Distrofia Muscular Animal/patologia , Junção Neuromuscular/ultraestrutura , Animais , Membrana Celular/ultraestrutura , Camundongos , Músculos/ultraestrutura , Necrose , Receptores Colinérgicos/análise , Membranas Sinápticas/ultraestruturaRESUMO
The placentas of 14 growth-retarded fetuses with abnormal umbilical artery velocimetry and 15 appropriately grown fetuses with normal waveforms were collected immediately after delivery and analyzed in a blinded fashion. A large percentage of the arterial vessels in the placentas from the former group showed abnormal changes in the vessel wall. The percentage of abnormal arterial vessels in all placentas correlated significantly with the resistance index. This study provides an anatomical basis for the elevated resistance to blood flow in placentas from growth-retarded fetuses.