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Background: FGF-21 is described as a powerful metabolic regulator with beneficial effects including glucose-lowering and improvement of insulin sensitivity without hypoglycaemia. On the other hand, FGF-21 is activated when muscle and other tissues are stressed by external effects or internal cellular pathogens that lead to shortcomings in metabolic balance. Previous results suggested that FGF-21 could be a promising target to develop future metabolic therapeutics., Purpose: The present study was performed to gain deeper insight into the regulation of FGF-21 by protein metabolism in obese human subjects., Methods: FGF-21 serum concentrations were measured in a cohort of n = 246 obese humans ± type 2 diabetes mellitus (T2DM) (median age 53.0 [46.0; 60.0] years and BMI 40.43 [35.11; 47.24] kg/m 2 ) and related to the nutritional protein intake. In addition, the effect of a novel oligopeptide purified from a β-casein hydrolysate on FGF-21 was examined in vitro in liver cells and in vivo in a human intervention study with the main focus on metabolic inflammation including 40 mainly obese subjects (mean age 41.08 ± 9.76 years, mean BMI 38.29 ± 9.4 kg/m 2 ) in a randomized 20 weeks double-blind cross-over design., Main Findings: In the cohort analysis, FGF-21 serum concentrations were significant lower with higher protein intake in obese subjects without T2DM but not in obese subjects with T2DM. Furthermore, relative methionine intake was inversely related to FGF-21. While global protein intake in obesity was inversely associated with FGF-21, incubation of HepG2 cells with a β-casein oligopeptide increased FGF-21 expression in vitro. This stimulatory effect was also present in vivo, since in the clinical intervention study treatment of obese subjects with the β-casein oligopeptide for 8 weeks significantly increased FGF-21 serum levels from W0 = 23.86 pg/mL to W8 = 30.54 pg/mL (p < 0.001), while no increase was found for placebo., Conclusion: While the total nutritional protein intake is inversely associated with FGF-21 serum levels, a purified and well characterised oligopeptide is able to induce FGF-21 serum levels in humans. These findings suggest a differential role of various components of protein metabolism on FGF-21, rather than this factor being solely a sensor of total nutritional protein intake., Competing Interests: Conflicts of interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

In this paper, we present a Bayesian framework for both generating inter-subject large deformation transformations between two multi-modal image sets of the brain and for forming multi-class brain atlases. In this framework, the estimated transformations are generated using maximal information about the underlying neuroanatomy present in each of the different modalities. This modality independent registration framework is achieved by jointly estimating the posterior probabilities associated with the multi-modal image sets and the high-dimensional registration transformations mapping these posteriors. To maximally use the information present in all the modalities for registration, Kullback-Leibler divergence between the estimated posteriors is minimized. Registration results for image sets composed of multi-modal MR images of healthy adult human brains are presented. Atlas formation results are presented for a population of five infant human brains.

Background: There is still a considerable controversy regarding optimal treatment for patients with acute type B aortic dissection. Patients with complicated disease are particularly challenging for cardiovascular treatment. Early surgery for acute dissections of the descending aorta with life-threatening complications is known to carry a high mortality. Endovascular stent grafting is developing as an alternative treatment mainly for chronic stages of type B aortic dissection. It is not clear whether endovascular stent grafting is safe and effective in emergency treatment of acute type B aortic dissection., Methods: In 10 patients (7 men, 3 women; mean age, 59.2 years; range, 46 to 65 years), endovascular stent grafting was performed within 11.0 +/- 5.9 hours (range, 4 to 24 hours) of diagnosis of complications. Indications for acute intervention included contained rupture, hematothorax, life-threatening malperfusion, and refractory pain. Using a retrograde endovascular route after surgical exposure of the femoral artery, self-expanding stent prostheses consisting of polyester-covered Nitinol (Talent, World Medical; mean diameter, 40 +/- 4 mm; length, 10 cm) were placed into the descending aorta distal to the subclavian artery. Before discharge and on follow-up visits, imaging of the aorta was performed using computed tomography., Results: In 9 of 10 patients (90%), the primary entry could be completely occluded with the endovascular stent. Early mortality was 20% (2 of 10): 1 patient died after disruption of the intimal layer distal to the stent, and 1 patient died in hemorrhagic shock after surgical fenestration of the abdominal aorta for persistent malperfusion. Three patients (30%) required consecutive surgical treatment: indications included acute development of retrograde type A aortic dissection, acute stent dislocation by fractured wires and secondary leakage, and late formation of an aneurysm of the descending aorta 6 months after endovascular stent grafting. There were no surgical or late deaths., Conclusions: Our experience provides some evidence that early mortality of life-threatening acute type B aortic dissection may be reduced by emergency endovascular stent grafting and that this form of treatment is a promising therapeutic option. Refinements, especially in stent design and application, may further improve the prognosis of patients in the life-threatening situation of complicated acute type B aortic dissection.

This paper presents a general framework for analyzing structural and radiometric asymmetry in brain images. In a healthy brain, the left and right hemispheres are largely symmetric across the mid-sagittal plane. Brain tumors may belong to one or both of the following categories: mass-effect, in which the diseased tissue displaces healthy tissue; and infiltrating, in which healthy tissue has become diseased. Mass-effect brain tumors cause structural asymmetry by displacing healthy tissue, and may cause radiometric asymmetry in adjacent normal structures due to edema. Infiltrating tumors have a different radiometric response from healthy tissue. Thus, structural and radiometric asymmetries across the mid-sagittal plane in brain images provide important cues that tumors may be present. We have developed a framework that registers images with their reflections across the mid-sagittal plane. The registration process accounts for tissue displacement through large deformation image warping. Radiometric differences are taken into account through an additive intensity field. We present an efficient multi-scale algorithm for the joint estimation of structural and radiometric asymmetry. Results for nine MR images of patients with tumors and four normal control subjects are presented.