Hypothalamic SIRT1-mediated regulation of the hormonal trigger of ovulation and its repression in energy deficit.

Female reproduction is highly sensitive to body energy stores; persistent energy deficit, as seen in anorexia or strenuous exercise, is known to suppress ovulation via ill-defined mechanisms. We report herein that hypothalamic SIRT1, a key component of the epigenetic machinery that links nutritional status and puberty onset via modulation of Kiss1, plays a critical role in the control of the preovulatory surge of gonadotropins, i.e.

Consensus Delphi study on guidelines for the assessment of anterior cruciate ligament injuries in children.

Background: Knee examination guidelines in minors are intended to aid decision-making in the management of knee instability.

Clinical Question: A Delphi study was conducted with a formal consensus process using a validated methodology with sufficient scientific evidence. A group consensus meeting was held to develop recommendations and practical guidelines for use in the assessment of instability injuries in children.

GLP-1-mediated delivery of tesaglitazar improves obesity and glucose metabolism in male mice.

Dual agonists activating the peroxisome proliferator-activated receptors alpha and gamma (PPARɑ/ɣ) have beneficial effects on glucose and lipid metabolism in patients with type 2 diabetes, but their development was discontinued due to potential adverse effects. Here we report the design and preclinical evaluation of a molecule that covalently links the PPARɑ/ɣ dual-agonist tesaglitazar to a GLP-1 receptor agonist (GLP-1RA) to allow for GLP-1R-dependent cellular delivery of tesaglitazar. GLP-1RA/tesaglitazar does not differ from the pharmacokinetically matched GLP-1RA in GLP-1R signalling, but shows GLP-1R-dependent PPARɣ-retinoic acid receptor heterodimerization and enhanced improvements of body weight, food intake and glucose metabolism relative to the GLP-1RA or tesaglitazar alone in obese male mice.

Early programming of reproductive health and fertility: novel neuroendocrine mechanisms and implications in reproductive medicine.

Background: According to the Developmental Origins of Health and Disease (DOHaD) hypothesis, environmental changes taking place during early maturational periods may alter normal development and predispose to the occurrence of diverse pathologies later in life. Indeed, adverse conditions during these critical developmental windows of high plasticity have been reported to alter the offspring developmental trajectory, causing permanent functional and structural perturbations that in the long term may enhance disease susceptibility. However, while solid evidence has documented that fluctuations in environmental factors, ranging from nutrient availability to chemicals, in early developmental stages (including the peri-conceptional period) have discernible programming effects that increase vulnerability to develop metabolic perturbations, the impact and eventual mechanisms involved, of such developmental alterations on the reproductive phenotype of offspring have received less attention.