PPARß/δ-dependent MSC metabolism determines their immunoregulatory properties.

Mesenchymal stem cell (MSC)-based therapy is being increasingly considered a powerful opportunity for several disorders based on MSC immunoregulatory properties. Nonetheless, MSC are versatile and plastic cells that require an efficient control of their features and functions for their optimal use in clinic. Recently, we have shown that PPARß/δ is pivotal for MSC immunoregulatory and therapeutic functions. However, the role of PPARß/δ on MSC metabolic activity and the relevance of PPARß/δ metabolic control on MSC immunosuppressive properties have never been addressed. Here, we demonstrate that PPARß/δ deficiency forces MSC metabolic adaptation increasing their glycolytic activity required for their immunoregulatory functions on Th1 and Th17 cells. Additionally, we show that the inhibition of the mitochondrial production of ATP in MSC expressing PPARß/δ, promotes their metabolic switch towards aerobic glycolysis to stably enhance their immunosuppressive capacities significantly. Altogether, these data demonstrate that PPARß/δ governs the immunoregulatory potential of MSC by dictating their metabolic reprogramming and pave the way for enhancing MSC immunoregulatory properties and counteracting their versatility.

Continuous pericapsular nerve group blockade as analgesia for fracture of the posterior column and wall of the acetabulum; a case report and description of infusion regimen for extending analgesic effect to the distal femoral area. / Bloqueo continuo del grupo de nervios pericapsular como analgesia para fractura de columna y pared posterior de acetábulo, reporte de caso y descripción de régimen de infusión para ampliar la cobertura analgésica a la región femoral distal.

The use of peripheral nerve blockade for hip surgeries has proved to be beneficial. The PEricapsular Nerve Group block is a new technique described for hip fracture and hip arthroplasty that has shown to provide better analgesia compared to other peripheral blocks commonly performed for this type of surgery. This technique blocks the obturator nerve and the articular branches of the femoral nerve and the accessory obturator nerve. There are few reports describing continuous analgesia using catheters inserted in the pericapsular nerve group area. We describe a case of continuous nerve block for preoperative analgesia that lasted up to 120hours in an adult patient with a fracture of the posterior column and wall of the acetabulum. We found that by increasing the infusion rate, analgesia reached the distal femoral area. Unlike the original technique, a high-frequency linear probe was used in this case.

Association of the melanocortin 4 receptor gene rs17782313 polymorphism with rewarding value of food and eating behavior in Chilean children.

Studies conducted in monozygotic and dizygotic twins have established a strong genetic component in eating behavior. Rare mutations and common variants of the melanocortin 4 receptor (MC4R) gene have been linked to obesity and eating behavior scores. However, few studies have assessed common variants in MC4R gene with the rewarding value of food in children. The objective of the study was to evaluate the association between the MC4R rs17782313 polymorphism with homeostatic and non-homeostatic eating behavior patterns in Chileans children. This is a cross-sectional study in 258 Chilean children (44 % female, 8-14 years old) showing a wide variation in BMI. Anthropometric measurements (weight, height, Z-score of BMI and waist circumference) were performed by standard procedures. Eating behavior was assessed using the Eating in Absence of Hunger Questionnaire (EAHQ), the Child Eating Behavior Questionnaire (CEBQ), the Three-Factor Eating Questionnaire (TFEQ), and the Food Reinforcement Value Questionnaire (FRVQ). Genotype of the rs17782313 nearby MC4R was determined by a Taqman assay. Association of the rs17782313 C allele with eating behavior was assessed using non-parametric tests. We found that children carrying the CC genotype have higher scores of food responsiveness (p value = 0.02). In obese girls, carriers of the C allele showed lower scores of satiety responsiveness (p value = 0.02) and higher scores of uncontrolled eating (p value = 0.01). Obese boys carrying the C allele showed lower rewarding value of food in relation to non-carriers. The rs17782313 C allele is associated with eating behavior traits that may predispose obese children to increased energy intake and obesity.