Epithelial layer unjamming shifts energy metabolism toward glycolysis.

In development of an embryo, healing of a wound, or progression of a carcinoma, a requisite event is collective epithelial cellular migration. For example, cells at the advancing front of a wound edge tend to migrate collectively, elongate substantially, and exert tractions more forcefully compared with cells many ranks behind. With regards to energy metabolism, striking spatial gradients have recently been reported in the wounded epithelium, as well as in the tumor, but within the wounded cell layer little is known about the link between mechanical events and underlying energy metabolism. Using the advancing confluent monolayer of MDCKII cells as a model system, here we report at single cell resolution the evolving spatiotemporal fields of cell migration speeds, cell shapes, and traction forces measured simultaneously with fields of multiple indices of cellular energy metabolism. Compared with the epithelial layer that is unwounded, which is non-migratory, solid-like and jammed, the leading edge of the advancing cell layer is shown to become progressively more migratory, fluid-like, and unjammed. In doing so the cytoplasmic redox ratio becomes progressively smaller, the NADH lifetime becomes progressively shorter, and the mitochondrial membrane potential and glucose uptake become progressively larger. These observations indicate that a metabolic shift toward glycolysis accompanies collective cellular migration but show, further, that this shift occurs throughout the cell layer, even in regions where associated changes in cell shapes, traction forces, and migration velocities have yet to penetrate. In characterizing the wound healing process these morphological, mechanical, and metabolic observations, taken on a cell-by-cell basis, comprise the most comprehensive set of biophysical data yet reported. Together, these data suggest the novel hypothesis that the unjammed phase evolved to accommodate fluid-like migratory dynamics during episodes of tissue wound healing, development, and plasticity, but is more energetically expensive compared with the jammed phase, which evolved to maintain a solid-like non-migratory state that is more energetically economical.

The Edmonton Obesity Staging System: assessing a potential tool to improve the management of obesity surgery in the Brazilian public health services.

BACKGROUND: Limited access to publicly funded, insurance-covered, and self-paid obesity surgery is a reality worldwide. Waiting lists for procedures are usually based on chronologic criteria and body mass index (BMI)-defined obesity categorization. Obesity classification systems assess overall health and have been proposed as an alternative. OBJECTIVE: To investigate the correlation between BMI-based classification and the Edmonton Obesity Staging System (EOSS) to support current evidence that the assessment of the clinical severity of obesity could be a helpful tool to maximize access to surgery. SETTING: University hospital, Brazil. METHODS: Retrospective analysis of all 2011 to 2014 adult patients who underwent obesity surgery under the public health system. Data on sex, age, presurgical BMI, and co-morbidities were extracted from hospital records. Spearman correlation coefficients were used to assess the strength and direction of the relationship between BMI classification and EOSS. RESULTS: Of 565 patients, 79% were female, mean age 44.1 ± 10.9 years and mean BMI 46.9 ± 6.2 kg/m2. The most common EOSS stage was 2 (86.5%), followed by stages 3 (8.5%) and 1 (4.9%). There was no correlation between the severity of obesity measured by BMI and EOSS (ρ = -.030, P = .475). Older patients had higher Edmonton scores (ρ = .308, P < .001). No difference was observed regarding sex. CONCLUSIONS: No correlation was found between EOSS and BMI and between these and sex. Age correlated with both obesity indicators. EOSS was reproducible in Brazilian surgical patients and may be an important tool from a health services perspective contributing to the more efficient use of limited resources for obesity surgery.