Weight-HbA1c-insulin-glucose model for describing disease progression of type 2 diabetes.

A previous semi-mechanistic model described changes in fasting serum insulin (FSI), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) in patients with type 2 diabetic mellitus (T2DM) by modeling insulin sensitivity and ß-cell function. It was later suggested that change in body weight could affect insulin sensitivity, which this study evaluated in a population model to describe the disease progression of T2DM. Nonlinear mixed effects modeling was performed on data from 181 obese patients with newly diagnosed T2DM managed with diet and exercise for 67 weeks. Baseline ß-cell function and insulin sensitivity were 61% and 25% of normal, respectively. Management with diet and exercise (mean change in body weight = -4.1 kg) was associated with an increase of insulin sensitivity (30.1%) at the end of the study. Changes in insulin sensitivity were associated with a decrease of FPG (range, 7.8-7.3 mmol/L) and HbA1c (6.7-6.4%). Weight change as an effector on insulin sensitivity was successfully evaluated in a semi-mechanistic population model.

The Richards type II patellofemoral arthroplasty: 26 cases followed for 1-20 years.

We followed 26 Richards type II patellofemoral arthroplasties in 24 patients (19 women) for a mean of 11 (1-20) years. Their mean age was 59 (22-90) years. The preoperative diagnoses were primary patellofemoral arthrosis in 17 cases and secondary arthrosis in 9 (8 malalignment, 1 patellar fracture). Patellectomy was later performed for persistent pain or patellar malalignment in 3 cases and a conversion to a total knee arthroplasty for progressive tibio-femoral degeneration or patella malalignment in 2. The mean Knee Society knee score for 21 knees at follow-up was 90 (65-100) points. The patients rated the results of surgery in 9 knees as excellent, 7 good, 4 improved, and 1 unimproved at follow-up. None of the implants showed signs of loosening or infection. The Richards type II patellofemoral arthroplasty yields acceptable long-term results in patients with isolated end-stage patellofemoral osteoarthrosis. Patient selection and patella alignment are important.

Evolutionary radiations and convergences in the structural organization of mammalian brains.

The sizes of mammalian brain components seem to be mostly related to the sizes of the whole brain (and body), suggesting a one-dimensional scale of encephalization. Previous multivariate study of such data concludes that evolutionary selection for enlargement of any one brain part is constrained to selection for a concerted enlargement of the whole brain. However, interactions between structurally related pairs of brain parts confirm reports of differential change in brain nuclei, and imply mosaic rather than concerted evolution. Here we analyse a large number of variables simultaneously using multi-dimensional methods. We show that the relative proportions of different systems of functionally integrated brain structures vary independently between different mammalian orders, demonstrating separate evolutionary radiations in mammalian brain organization. Within each major order we identify clusters of unrelated species that occupy similar behavioural niches and have convergently evolved similar brain proportions. We conclude that within orders, mosaic brain organization is caused by selective adaptation, whereas between orders it suggests an interplay between selection and constraints.