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BACKGROUND AND AIMS: Obesity is a key contributing factor to incidental type 2 diabetes and cardiovascular disease. CXCR3 receptor and its ligands CXCL 10 and 11 are associated with atherosclerosis and cardiovascular disease. The aim of our study was to analyse the role of the CXCR3 ligands on insulin resistance (IR) and endothelial dysfunction in human obesity. METHODS AND RESULTS: We have studied 45 obese patients (mean age 44?±?6?years, body mass index 45?±?9?kg/m2) who were selected for Roux-Y-gastric bypass surgery and 21 non obese control subjects with similar age and gender distribution. We measured by ELISA the circulating levels of the CXCR3 ligands interferon-gamma inducible protein 10 (IP-10/CXCL10) and interferon-gamma-inducible T-cell alpha chemoattractant (I-TAC/CXCL11). Using an ex vivo procedure with the flow chamber assay, we have investigated the effect of such chemokines on endothelial leukocytes arrest under dynamic conditions. Peripheral blood levels of CXCL10 and CXCL11 were significantly higher in obese subjects than in controls (p?0.001) and significantly correlated with BMI, waist circunference and HOMA-IR. Obese patients with HOMA-IR index above 75th percentile showed highest increase of circulating CXCL10 and CXCL11 values. Under dynamic flow conditions, the enhanced adhesion of patient leukocytes to TNFalpha-induced human arterial endothelial cells was partly dependent on CXCR3. CONCLUSIONS: The study demonstrates that CXCL10 and CXCL11 are associated with IR and enhance leukocyte endothelial arrest in obese subjects. Blockade of CXCR3 signaling might be a new therapeutic approach for the prevention of obesity-associated cardiovascular co-morbidities.

BACKGROUND: Obesity is associated with high cardiovascular risk. Postprandial lipidemia has been associated with cardiovascular disease risk. Our aim was to identify whether anthropometric parameters, insulin resistance (IR) and/or fasting plasma triglycerides may determine postprandial changes in lipoprotein concentrations in abdominal and morbid obese subjects. METHODS: we have studied 20 non-diabetic, normolipidemic subjects with abdominal obesity, 20 morbid obese subjects and 20 healthy individuals, that have similar age and gender. In all of them a standardized oral fat load test (OFLT) with unsaturated fat was performed. RESULTS: during the OFLT, the postprandial triglycerides response was significantly higher in subjects with abdominal obesity compared to morbid obese subjects (4 hours triglycerides pick value and AUC of triglycerides). Both obese groups showed significantly higher postprandial triglycerides response compared to healthy subjects. Dividing the obesity group according to the presence of IR, we found that IR was an important factor related with postprandial lipemia but not BMI or waist circumference. In addition, postprandial glycemia and insulinemia significantly decreased in all studied subjects, being the highest decrease in morbid obese subjects and in subjects with IR. Postprandial triglyceridemia significantly correlated with IR parameters and not with anthropometric parameters in AO and MO subjects. CONCLUSION: in subjects with AO and MO, postprandial triglycerides values are higher than healthy individuals and independently predicted by fasting IR parameters. Furthermore, unsaturated fat improved IR state.

BACKGROUND/AIMS: Inflammation governs adipose tissue (AT) dysfunction in obesity. Retinoic acid receptor-related orphan receptor alpha (RORalpha) is associated with inflammation and insulin resistance in animal studies, but its role in human obesity remains elusive. We investigated the expression and function of RORalpha on AT inflammation in patients with morbid obesity with/without diabetes. SUBJECTS/METHODS: We assessed RORalpha expression in paired biopsies of subcutaneous and omental AT from 41 patients (body mass index (BMI) 43.3±0.8kg/m2) during Roux-en-Y-gastric surgery and explored the functional consequences of pharmacological RORalpha blockade in AT ex vivo. RESULTS: RORalpha expression was significantly higher in omental AT than in subcutaneous AT (p=0.03) and was positively associated with BMI (r=0.344, p=0.027) and homeostasis model assessment of insulin resistance (r=0.319, p=0.041). In ex vivo assays, IL-8/CXCL8 and MCP-1/CCL2 chemokine release was significantly higher in omental fat explants from diabetic patients than from non-diabetics and was significantly diminished by RORalpha blockade (p

Aging has increased the prevalence of frailty, and type 2 diabetes (T2D) has also increased in prevalence. Diabetes and oxidative stress (OS) have been shown to be related to frailty. However, the exact mechanism by which it occurs is not fully known. Our aim was to analyze body composition in community-dwelling older diabetic people treated in our center and to evaluate the possible relation between OS, frailty, and body composition. We included 100 adults older than 65 years with T2D. We found that 15% were frail and 57% were prefrail. The patients included in the nonrobust group showed increased levels of OS. Our study shows that the presence of T2D in the geriatric population is associated with a high prevalence of frailty and high OS levels, conditions that cause greater morbidity and mortality and that highlight the importance of the diagnosis of frailty in this population.

OBJECTIVE: Post-prandial lipaemia (PL), oxidative stress (OS), and complement component C3 (C3) values are related to the atherosclerosis process. The post-prandial response of C3 after an oral fat load test (OFLT) using unsaturated fat is poorly addressed. The aim of this study was to analyze and compare the post-prandial response of OS markers and C3 values in men and women after an OFLT using unsaturated fat.; METHODS: The study included a total of 22 healthy subjects with normal lipids and normal blood glucose (11 men and 11 pre-menopausal women). An oral unsaturated fat load test (OFLT: 50g fat per m2 body surface) was performed using a commercial liquid preparation of long chain triglycerides (Supracal). OS markers and C3 were measured using standardized methods at fasting state and every 2h up to 8h after the OFLT.; RESULTS: Men showed statistically significant higher C3, oxidized glutathione (GSSG), and oxidized-reduced glutathione (GSSG/GSH) ratio values at fasting state compared to that obtained in women. In addition, post-prandial C3 values and GSSG/GSH ratios were significantly higher in men compared to women. The GSSG value and GSSG/GSH ratio significantly decreased in men after the OFLT compared to fasting values. In contrast, the post-prandial OS markers decrease observed in women was not statistically significant.; CONCLUSIONS: In fasting state, men showed higher statistically significant C3 values and OS markers than women. The post-prandial OS markers (GSSG and GSSG/GSH ratio) significantly decrease after the OFLT with unsaturated fat in men compared to women. Copyright © 2019 Sociedad Espanola de Arteriosclerosis. Publicado por Elsevier Espana, S.L.U. All rights reserved.

Background: Thyroid abscess or acute suppurative thyroiditis is an unusual clinical condition. We present our experience with cases attended over 41 years. Materials and methods: A retrospective study was performed on these patients reviewing their epidemiological characteristics and the diagnostic and therapeutic manoeuvres chosen for them all, as well as their clinical outcome. A group of 9 males and 5 females was studied, with ages ranging from 19 to 68 (mean of 40.6 +/- 15.4). These patients suffered 22 acute episodes, and 2 patients each had 4 episodes. Results: Suppurative thyroiditis comprised 0.29% of the neck abscesses. Fine needle aspiration was performed in 13 cases to evacuate the collection and isolate the aetiological agent. Mycobacterium tuberculosis and Staphylococcus aureus were the most frequently identified. Nine patients underwent ultrasound and 7 computed tomography imaging studies. Surgery was the option for 10 patients, including drainage for 7, thyroidectomy for 4 and hemithyroidectomy for the remaining 2. Systemic or intratesional antibiotics and sclerosis of the gland were also carried out. Although one case presented with hyperthyroidism and thyrotoxicosis in the acute phase, definitive hypothyroidism was observed in 5 patients at 6 months following discharge. The rate of success was 100%. Conclusion: Thyroid gland suppuration is a very infrequent circumstance in neck pathology, and the options for its treatment are varied, from conservative to invasive techniques according to the microbial and radiotogic findings. (C) 2018 Sociedad Espanola de Otorrinolaringologia y Cirugia de Cabeza y Cuello. Published by Elsevier Espana, S.L.U. All rights reserved.

For some years, there has been interest in locating cracks in beams by detecting singularities in mode shape curvatures. Most of the work in the past has depended on the estimation of spatial derivatives (smoothed or otherwise) of the experimentally measured mode shape. This problem is made difficult by the fact that numerical differentiation is notorious for amplifying measurement noise, coupled with that fact that very precise estimates of mode shapes are difficult to obtain. One recent approach, introduced by one of the authors, circumvented the noise issue via a method which did not need numerical differentiation. Briefly, the method applied a Gaussian process regression to the data, using a covariance function that could switch between spatial regions; the switch point—which indicated the crack position—could be determined by a maximum likelihood algorithm. The object of the current paper is to present an alternative approach which uses Treed Gaussian Processes (TGPs). The idea is that separate Gaussian Processes, with standard covariance functions, can be fitted over different spatial regions of the beam, with any switching points learned as part of a decision tree structure. The paper also revisits the idea of using differentiated mode shapes, on the premise that the Gaussian process can ‘see through’ the noise created and perceive the underlying structure.

We have designed a new synthetic strategy for the preparation of a new class of cyclic RGD integrin ligands in which the azabicycloalkane scaffold can be envisaged as a (gamma,alpha) dipeptide mimic. The synthesis and in vitro biological evaluation of these RGD derivatives, as well as the computational study of their conformational properties and binding modes to alpha(V)beta(3) integrin are described. Compound 3 has shown to be a promising candidate as alpha(V)beta(3) integrin antagonist able to interfere with both cell adhesion and movement on vitronectin with no evidence of cytotoxic effects.

Mutations underlying FH in Spain are largely unknown because only a few and limited surveys have been carried out on Spanish FH patients up to now. To gain information on this issue, we have analysed a group of 113 unrelated Spanish FH patients from an eastern area of Spain (Valencian Community). We have screened the LDLR gene by Southern blot and PCR-SSCP analysis to detect large rearrangements and small mutations, respectively. In addition, we have screened the Apo B gene for mutations known to cause FDB by PCR-SSCP analysis. We have identified a total of 47 different mutations in the LDLR gene (5 large rearrangements, and 42 small mutations, which were characterized by DNA sequencing), 19 of which have not been described in other populations (Valencia-1 to -4, 112insA, P160R, 790DelATGA, 920insTCAG, G642E, and the ten novel mutations E246A, 884delT, I289T, S305F, Q328X, Y354C, I603del, 2312-3CA, V779M, and N804K). Three of these mutations (15%) were present in more than 1 proband, being mutation 112insA the most prevalent (frequency approximately 8%) in our sample. The Apo B gene R3500Q mutation was found in only one patient and no underlying defect was found in about 27% of patients. Our data support the notion that Spaniards represent a heterogeneous population with its own spectrum of LDLR gene mutations and that, in our population, FDB has a lower frequency or a milder expression than in central Europe countries.