TIMP3 interplays with apelin to regulate cardiovascular metabolism in hypercholesterolemic mice

Tissue inhibitor of metalloproteinase 3 (TIMP3) is an extracellular matrix (ECM) bound protein, which has been shown to be downregulated in human subjects and experimental models with cardiometabolic disorders, including type 2 diabetes mellitus, hypertension and atherosclerosis. The aim of this study was to investigate the effects of TIMP3 on cardiac energy homeostasis during increased metabolic stress conditions

Temperature cycling of complex profiles FIDES

De plus en plus d’industriels se tournent vers des modèles de fiabilité récents comme FIDES. Ces modèles permettent de saisir de manière réaliste les profils de vie et introduisent un nouveau facteur prépondérant dans la prédiction de la fiabilité qui est la notion de cyclage en température. Les anciens modèlesde fiabilité (tel que la MIL-HDBK-217F) ne permettaient pas de modéliser l’accélération apportée par les variations thermiques sur le mécanisme de fatigue thermomécanique. Le codage du profil de vie est une étape cruciale dans l’élaboration de la fiabilité des systèmes électroniques. La méthode proposée par Sagem DS permet de saisir efficacement les profils de vie, en particulier pour les phénomènes de cyclage en température, et d’appréhender les cas dits « complexes ». Lors de la présentation au λμ, Sagem DS exposera différents cas « complexes » de profils en majorité aéronautiques et certains militaires afin d’illustrer la mise en application de la méthode proposée.More and more industries are interested in recent reliability handbooks as FIDES. These models allow to capture realistically life profiles and introduce a new important factor for reliability prediction which is the temperature cycling. Former reliability models (such as MIL-HDBK-217F) do not allow to model the acceleration provided by thermal variations on thermo-mechanical fatigue mechanism. Life profile coding phase is a crucial step for electronic design reliability assessment. The method proposed by Sagem DS allow to effectively capture life profiles, especially for temperature cycling phenomenal, and allow to deal with “complex” cases. During the λμ presentation, Sagem DS will present different “complex” cases of mostly aeronautical profiles and some militaries to illustrate the application of the proposed method

The angiogenic factor PIGF mediates a neuroimmune interaction in the spleen to allow the onset of hypertension

Hypertension is a health problem affecting over 1 billion people worldwide. How the immune system gets activated under hypertensive stimuli to contribute to blood pressure elevation is a fascinating enigma. Here we showed a splenic role for placental growth factor (PlGF), which accounts for the onset of hypertension, through immune system modulation. PlGF repressed the expression of the protein Timp3 (tissue inhibitor of metalloproteinases 3), through the transcriptional Sirt1-p53 axis. Timp3 repression allowed costimulation of T cells and their deployment toward classical organs involved in hypertension. We showed that the spleen is an essential organ for the development of hypertension through a noradrenergic drive mediated by the celiac ganglion efferent. Overall, we demonstrate that PlGF mediates the neuroimmune interaction in the spleen, organizing a unique and nonredundant response that allows the onset of hypertension

Comparing population structure as inferred from genealogical versus genetic information

Algorithms for inferring population structure from genetic data (ie, population assignment methods) have shown to effectively recognize genetic clusters in human populations. However, their performance in identifying groups of genealogically related individuals, especially in scanty-differentiated populations, has not been tested empirically thus far. For this study, we had access to both genealogical and genetic data from two closely related, isolated villages in southern Italy. We found that nearly all living individuals were included in a single pedigree, with multiple inbreeding loops. Despite Fst between villages being a low 0.008, genetic clustering analysis identified two clusters roughly corresponding to the two villages. Average kinship between individuals (estimated from genealogies) increased at increasing values of group membership (estimated from the genetic data), showing that the observed genetic clusters represent individuals who are more closely related to each other than to random members of the population. Further, average kinship within clusters and Fst between clusters increases with increasingly stringent membership threshold requirements. We conclude that a limited number of genetic markers is sufficient to detect structuring, and that the results of genetic analyses faithfully mirror the structuring inferred from detailed analyses of population genealogies, even when Fst values are low, as in the case of the two villages. We then estimate the impact of observed levels of population structure on association studies using simulated data

Glaucopine C, a new diterpene from the fruiting bodies of Sarcodon glaucopus.

In this work the mushroom Sarcodon glaucopus was studied. A new cyathane, glaucopine C (1), was isolated from the hexane extract and identified by 1H and 13C NMR spectra analysis. Glaucopine C showed anti-inflammatory acitvity

Combined Use of Skin Needling and Platelet-Rich Plasma in Acne Scarring Treatment.

Platelet-rich plasma (PRP) contains autologous growth factors, which could act synergistically with growth factors induced by skin needling in order to enhance the wound-healing response. The com- bination of treatments, carried out by using skin needling and PRP application, should enhance both efficacy of skin needling and PRP application. The objective of this study is to establish the effectiveness of the combined use of skin needling and PRP application in acne scarring treatment. Twelve patients affected with rolling acne scars were enrolled. Each patient underwent 2 sessions of treatments, each consisting of skin needling followed by PRP application on the right side of the face and skin needling alone on the left side of the face. Digital photographs of all patients were taken. Photographic data were analyzed by using the Sign Test (a,.05). The study showed that the scars severity grade in all patients was greatly reduced on all of the face, but the improvement was more efficient on the side treated with both skin needling and PRP. Our study showed that the combined use of skin needling and PRP is more effective than skin needling alone in improving acne scars

High sodium intake is associated with increased glucocorticoid production, insulin resistance and metabolic syndrome.

OBJECTIVE: High sodium (HS) diet is associated with hypertension (HT) and insulin resistance (IR). We evaluated whether HS diet was associated with a dysregulation of cortisol production and metabolic syndrome (MetS). PATIENTS AND MEASUREMENTS: We recruited 370 adults (18-85 years, BMI 29\ub73 \ub1 4\ub74 kg/m(2) , 70% women, 72% HT, 61% MetS). HS diet (urinary sodium >150 mEq/day) was observed in 70% of subjects. We measured plasma hormones, lipid profile, urinary free cortisol (UFC) and cortisol tetrahydrometabolites (THM). RESULTS: Urinary sodium was correlated with UFC (r = +0\ub745, P < 0\ub7001), cortisol THM (r = +0\ub741, P < 0\ub7001) and inversely with adiponectin, HDL and aldosterone, after adjusting by age, gender and BMI. Subjects with high, compared with adequate sodium intake (50-149 mEq/day) had higher UFC (P < 0\ub7001), THM (P < 0\ub7001), HOMA-IR (P = 0\ub704), HT (81% vs 50%, P < 0\ub7001), MetS (69% vs 41%, P < 0\ub7001) and lower adiponectin (P = 0\ub7003). A multivariate predictive model adjusted by confounders showed a high discriminative capacity for MetS (ROC curve 0\ub7878) using four clinical variables: HS intake [OR = 5\ub76 (CI 2\ub73-15\ub73)], HOMA-IR [OR 1\ub77 (1\ub73-2\ub72)] cortisol THM [OR 1\ub72 (1\ub71-1\ub74)] and adiponectin [OR = 0\ub79 (0\ub78-0\ub79)], the latter had a protective effect. CONCLUSIONS: High sodium diet was associated with increased urinary cortisol and its metabolites. Also, HS diet was associated with HT, insulin resistance, dyslipidaemia and hypoadiponectinaemia, even when adjusting by confounding variables. Further, we observed that high salt intake, IR and higher cortisol metabolites, alone or combined in a clinical simple model, accurately predicted MetS status, suggesting an additive mechanism in obesity-related metabolic disorders

Hypertension induces brain β-amyloid accumulation, cognitive impairment, and memory deterioration through activation of receptor for advanced glycation end products in brain vasculature

Although epidemiological data associate hypertension with a strong predisposition to develop Alzheimer disease, no mechanistic explanation exists so far. We developed a model of hypertension, obtained by transverse aortic constriction, leading to alterations typical of Alzheimer disease, such as amyloid plaques, neuroinflammation, blood-brain barrier dysfunction, and cognitive impairment, shown here for the first time. The aim of this work was to investigate the mechanisms involved in Alzheimer disease of hypertensive mice. We focused on receptor for advanced glycation end products (RAGE) that critically regulates Aβ transport at the blood-brain barrier and could be influenced by vascular factors. The hypertensive challenge had an early and sustained effect on RAGE upregulation in brain vessels of the cortex and hippocampus. Interestingly, RAGE inhibition protected from hypertension-induced Alzheimer pathology, as showed by rescue from cognitive impairment and parenchymal Aβ deposition. The increased RAGE expression in transverse aortic coarctation mice was induced by increased circulating advanced glycation end products and sustained by their later deposition in brain vessels. Interestingly, a daily treatment with an advanced glycation end product inhibitor or antioxidant prevented the development of Alzheimer traits. So far, Alzheimer pathology in experimental animal models has been recognized using only transgenic mice overexpressing amyloid precursor. This is the first study demonstrating that a chronic vascular insult can activate brain vascular RAGE, favoring parenchymal Aβ deposition and the onset of cognitive deterioration. Overall we demonstrate that RAGE activation in brain vessels is a crucial pathogenetic event in hypertension-induced Alzheimer disease, suggesting that inhibiting this target can limit the onset of vascular-related Alzheimer disease