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1.
Proc Natl Acad Sci U S A ; 119(49): e2201600119, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36454762

RESUMO

The direction in which a cell divides is set by the orientation of its mitotic spindle and is important for determining cell fate, controlling tissue shape, and maintaining tissue architecture. Divisions parallel to the epithelial plane sustain tissue expansion. By contrast, divisions perpendicular to the plane promote tissue stratification and lead to the loss of epithelial cells from the tissue-an event that has been suggested to promote metastasis. Much is known about the molecular machinery involved in orienting the spindle, but less is known about the contribution of mechanical factors, such as tissue tension, in ensuring spindle orientation in the plane of the epithelium. This is important as epithelia are continuously subjected to mechanical stresses. To explore this further, we subjected suspended epithelial monolayers devoid of extracellular matrix to varying levels of tissue tension to study the orientation of cell divisions relative to the tissue plane. This analysis revealed that lowering tissue tension by compressing epithelial monolayers or by inhibiting myosin contractility increased the frequency of out-of-plane divisions. Reciprocally, increasing tissue tension by elevating cell contractility or by tissue stretching restored accurate in-plane cell divisions. Moreover, a characterization of the geometry of cells within these epithelia suggested that spindles can sense tissue tension through its impact on tension at subcellular surfaces, independently of their shape. Overall, these data suggest that accurate spindle orientation in the plane of the epithelium relies on a threshold level of tension at intercellular junctions.


Assuntos
Células Epiteliais , Junções Intercelulares , Epitélio , Divisão Celular , Matriz Extracelular
2.
Artigo em Inglês | MEDLINE | ID: mdl-29851194

RESUMO

OBJECTIVE: Studies exploring the incidence and impact of the psychomotor subtypes of postoperative delirium (POD) on the survival of hip fracture patients are few, and results are inconsistent. We sought to assess the incidence of POD subtypes and their impact, in addition to delirium duration, on 6-month mortality in older patients after hip-fracture surgery. METHODS: This is a prospective study involving 571 individuals admitted to an Orthogeriatric Unit within a 5-year period with a diagnosis of hip fracture. Survival status was assessed 6 months after posthip fracture surgery. Postoperative delirium was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders. Postoperative delirium subtypes were classified according to Lipowski's criteria. Cox regressions were used to evaluate the associations between POD subtypes, POD duration, and 6-month mortality, adjusting for covariates. RESULTS: The incidence of psychomotor POD subtypes was hypoactive 57 (10.0%), hyperactive 84 (14.7%), and mixed 79 (13.8%). Six-month mortality rates were 8.3%, 10.7%, 36.8%, and 29.1% in the no-delirium, hyperactive, hypoactive, and mixed-delirium subgroups, respectively. In adjusted models, the hypoactive subgroup (Hazard Ratio, HR = 3.14, 95% Confidence Intervals, CI, 1.63-6.04) and mixed subgroup (HR = 2.89, 95% CI, 1.49-5.62) showed high mortality rates and a significantly increased risk of mortality associated with POD duration as well. CONCLUSIONS: Hyperactive delirium was the most common POD psychomotor subtype, but hypoactive and mixed POD were associated with 6-month mortality risk. Moreover, the risk of death 6 months after surgery increased for both subgroups (hypoactive and mixed) with increasing duration of POD.

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