Platelet Apoptotic Response May Be Associated With the Capacity of Aspirin to Inhibit Platelets.

An inadequate platelet response to aspirin (ASA) has been identified in some patients under chronic ASA treatment. The aim of this study was to analyze if ASA-sensitive and ASA-resistant platelets have differences in their apoptotic capability. Clinically stable ischemic coronary patients who had been taking ASA (100 mg/d) for at least 9 months before inclusion were divided into ASA-resistant (n = 11) and ASA-sensitive (n = 13) groups as defined by the PFA-100 test. Platelets from ASA-sensitive patients showed higher expression of the proapoptotic proteins Bak and Bax than those from ASA-resistant patients, although only Bak protein remained different when the results were adjusted by age. In resting platelets, neither caspase-3 activity nor cytosolic cytochrome C levels were different between both experimental groups. Stimulation of platelets with calcium ionophore (10 nmol/L, A23187) increased caspase-3 activity (1.91-fold higher; P < 0.05) and cytosolic cytochrome C levels (1.84-fold higher; P < 0.05) to a higher degree in ASA-sensitive than in ASA-resistant platelets. In conclusion, ASA-sensitive platelets seem to be better prepared to undergo apoptosis during robust platelet activation.

Factor Xa Inhibition by Rivaroxaban Modified Mitochondrial-Associated Proteins in Human Abdominal Aortic Aneurysms.

BACKGROUND: The presence of intraluminal thrombus and mitochondrial dysfunction in human abdominal aortic aneurysms (AAAs) have been associated with aneurysmal growth and rupture. The objective of the study was to study if endogenous factor Xa (FXa) may modulate mitochondrial functionality and expression of proteins associated with mitophagy in human AAAs. METHODS: AAA sites with intraluminal thrombus were obtained from 6 patients undergoing elective AAA surgery repair. Control samples were collected from 6 organ donors. The effect of FXa was analyzed by in vitro incubation of AAA with 50 nmol/L rivaroxaban, an oral FXa inhibitor. RESULTS: The enzymatic activities of citrate synthase, a biomarker of mitochondrial density, and cytochrome C oxidase, a biomarker of mitochondrial respiratory chain functionality, were significantly reduced in the AAA sites with respect to the healthy aorta (citrate synthase activity in µU/min/µg protein: control: 3.51 ± 0.22 vs. AAA: 0.37 ± 0.15.; P < 0.01; cytochrome C oxidase activity in µOD/min/µg protein: control: 8.05 ± 1.57 vs. AAA: 3.29 ± 1.05; P < 0.05). The addition of rivaroxaban to AAA reverted the activity of both citrate synthase and cytochrome C oxidase to similar values to control. Mitochondrial Drp-1 expression was higher in AAA sites than in either control aortas or rivaroxaban-incubated AAA sites. Cytosolic content of Drp-1 phosphorylated at Ser637, mitochondrial Parkin, and mitochondrial PINK1-Parkin interaction were significantly reduced in the AAA sites with respect to control aortas. For all these parameters, rivaroxaban-incubated AAA showed similar values compared with control aortas. CONCLUSIONS: In human AAA, rivaroxaban improved mitochondrial functionality that was associated with changes in proteins related to mitophagy. Its opens possible new effects of endogenous FXa on the mitochondria in the human AAA site.

Interaction between cardiovascular risk factors and body mass index and 10-year incidence of cardiovascular disease, cancer death, and overall mortality.

The effect of above-normal body mass index (BMI) on health outcomes is controversial because it is difficult to distinguish from the effect due to BMI-associated cardiovascular risk factors. The objective was to analyze the impact on 10-year incidence of cardiovascular disease, cancer deaths and overall mortality of the interaction between cardiovascular risk factors and BMI. We conducted a pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79years old at basal examination. Body mass index was measured at baseline being the outcome measures ten-year cardiovascular disease, cancer and overall mortality. Multivariable analyses were adjusted for potential confounders, considering the significant interactions with cardiovascular risk factors. We included 54,446 individuals (46.5% with overweight and 27.8% with obesity). After considering the significant interactions, the 10-year risk of cardiovascular disease was significantly increased in women with overweight and obesity [Hazard Ratio=2.34 (95% confidence interval: 1.19-4.61) and 5.65 (1.54-20.73), respectively]. Overweight and obesity significantly increased the risk of cancer death in women [3.98 (1.53-10.37) and 11.61 (1.93-69.72)]. Finally, obese men had an increased risk of cancer death and overall mortality [1.62 (1.03-2.54) and 1.34 (1.01-1.76), respectively]. In conclusion, overweight and obesity significantly increased the risk of cancer death and of fatal and non-fatal cardiovascular disease in women; whereas obese men had a significantly higher risk of death for all causes and for cancer. Cardiovascular risk factors may act as effect modifiers in these associations.

Nitric oxide from mononuclear cells may be involved in platelet responsiveness to aspirin.

BACKGROUND: Several mechanisms have been proposed to explain why some platelets have a reduced response to aspirin (ASA). Among them, it was reported an increased circulating level of vitamin-D-binding protein (DBP). In addition, nitric oxide (NO) released from mononuclear cells was involved in the antiplatelet effects of ASA. The aim was to analyse the relationship between platelet response to ASA and both NO generation and vitamin-D-binding protein content in mononuclear cells. MATERIALS AND METHODS: Mononuclear cells were obtained from patients with stable coronary artery disease that were divided by a platelet functionality test (PFA-100) as ASA-sensitive (n=23) and ASA resistant (n=27). RESULTS: Both the release of NO (determined by nitrite+nitrate concentration) and the expression of endothelial-type NO synthase (eNOS) were higher in mononuclear cells from ASA sensitive as compared with those from ASA-resistant patients. There was a positive correlation between either the release of NO and the expression of eNOS protein in mononuclear cells with the ability of ASA to inhibit platelet activity. DBP content in mononuclear cells was higher in ASA resistant than in ASA sensitive. The level of DBP content in mononuclear cells was negatively associated with the ability of ASA to inhibit platelets. However, in vitro experiments suggested that there was no association between DBP and NO production by mononuclear cells. CONCLUSIONS: Mononuclear cells from patients with platelets with lower responsiveness to ASA showed a reduced ability to produce NO.

Effects of factor Xa on the expression of proteins in femoral arteries from type 2 diabetic patients.

AIM: Further to its pivotal role in haemostasis, factor Xa (FXa) promotes effects on the vascular wall. The purpose of the study was to evaluate if FXa modifies the expression level of energy metabolism and oxidative stress-related proteins in femoral arteries obtained from type 2 diabetic patients with end-stage vasculopathy. METHODS: Femoral arteries were obtained from 12 type 2 diabetic patients who underwent leg amputation. Segments from the femoral arteries were incubated in vitro alone and in the presence of 25 nmol l(-1) FXa and 25 nmol l(-1) FXa + 50 nmol l(-1) rivaroxaban. RESULTS: In the femoral arteries, FXa increased triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase isotype 1 expression but decreased pyruvate dehydrogenase expression. These facts were accompanied by an increased content of acetyl-CoA. Aconitase activity was reduced in FXa-incubated femoral arteries as compared with control. Moreover, FXa increased the protein expression level of oxidative stress-related proteins which was accompanied by an increased malonyldialdehyde arterial content. The FXa inhibitor, rivaroxaban, failed to prevent the reduced expression of pyruvate dehydrogenase induced by FXa but reduced acetyl-CoA content and reverted the decreased aconitase activity observed with FXa alone. Rivaroxaban + FXa but not FXa alone increased the expression level of carnitine palmitoyltransferase I and II, two mitochondrial long chain fatty acid transporters. Rivaroxaban also prevented the increased expression of oxidative stress-related proteins induced by FXa alone. CONCLUSIONS: In femoral isolated arteries from type 2 diabetic patients with end-stage vasculopathy, FXa promoted disruption of the aerobic mitochondrial metabolism. Rivaroxaban prevented such effects and even seemed to favour long chain fatty acid transport into mitochondria.

Derivation and validation of a set of 10-year cardiovascular risk predictive functions in Spain: the FRESCO Study.

OBJECTIVE: To derive and validate a set of functions to predict coronary heart disease (CHD) and stroke, and validate the Framingham-REGICOR function. METHOD: Pooled analysis of 11 population-based Spanish cohorts (1992-2005) with 50,408 eligible participants. Baseline smoking, diabetes, systolic blood pressure (SBP), lipid profile, and body mass index were recorded. A ten-year follow-up included re-examinations/telephone contact and cross-linkage with mortality registries. For each sex, two models were fitted for CHD, stroke, and both end-points combined: model A was adjusted for age, smoking, and body mass index and model B for age, smoking, diabetes, SBP, total and HDL cholesterol, and for hypertension treatment by SBP, and age by smoking and by SBP interactions. RESULTS: The 9.3-year median follow-up accumulated 2973 cardiovascular events. The C-statistic improved from model A to model B for CHD (0.66 to 0.71 for men; 0.70 to 0.74 for women) and the combined CHD-stroke end-points (0.68 to 0.71; 0.72 to 0.75, respectively), but not for stroke alone. Framingham-REGICOR had similar C-statistics but overestimated CHD risk. CONCLUSIONS: The new functions accurately estimate 10-year stroke and CHD risk in the adult population of a typical southern European country. The Framingham-REGICOR function provided similar CHD prediction but overestimated risk.

Mussel-Inspired Sonochemical Nanocomposite Coating on Catheters for Prevention of Urinary Infections.

Catheter-associated urinary tract infections are the most common hospital-acquired infections and cause patient discomfort, increased morbidity, and prolonged stays, altogether posing a huge burden on healthcare services. Colonization occurs upon insertion, or later by ascending microbes from the rich periurethral flora, and is therefore virtually unavoidable by medical procedures. Importantly, the dwell time is a significant risk factor for bacteriuria because it gives biofilms time to develop and mature. This is why we engineer antibacterial and antibiofilm coating through ultrasound- and nanoparticle-assisted self-assembly on silicone surfaces and validate it thoroughly in vitro and in vivo. To this end, we combine bimetallic silver/gold nanoparticles, which exercise both biocidal and structural roles, with dopamine-modified gelatin in a facile and substrate-independent sonochemical coating process. The latter mussel-inspired bioadhesive potentiates the activity and durability of the coating while attenuating the intrinsic toxicity of silver. As a result, our approach effectively reduces biofilm formation in a hydrodynamic model of the human bladder and prevents bacteriuria in catheterized rabbits during a week of placement, outperforming conventional silicone catheters. These results substantiate the practical use of nanoparticle-biopolymer composites in combination with ultrasound for the antimicrobial functionalization of indwelling medical devices.

Enzymatically Built Nanoenabled Antimicrobial Coating on Urinary Catheters.

Catheter-associated urinary tract infections represent a major share of nosocomial infections, and are associated with longer periods of hospitalization and a huge financial burden. Currently, there are only a handful of commercial materials that reduce biofilm formation on urinary catheters, mostly relying on silver alloys. Therefore, we combined silver-phenolated lignin nanoparticles with poly(carboxybetaine) zwitterions to build a composite antibiotic-free coating with bactericidal and antifouling properties. Importantly, the versatile lignin chemistry enabled the formation of the coating in situ, enabling both the nanoparticle grafting and the radical polymerization by using only the oxidative activity of laccase. The resulting surface efficiently prevented nonspecific protein adsorption and reduced the bacterial viability on the catheter surface by more than 2 logs under hydrodynamic flow, without exhibiting any apparent signs of cytotoxicity. Moreover, the said functionality was maintained over a week both in vitro and in vivo, whereby the animal models showed excellent biocompatibility.

Vardenafil improves penile erection in type 2 diabetes mellitus patients with erectile dysfunction: role of tropomyosin.

INTRODUCTION: Evidences have been suggested that phosphodiesterase type 5 (PDE5) inhibition promotes vasculoprotective benefits in patients with cardiovascular diseases. AIM: The aim of this study is to analyze the systemic effect of PDE5 inhibition in type 2 diabetes mellitus patients with erectile dysfunction (ED) determining changes in the expression levels of plasma proteins. METHODS: Seventeen patients with controlled type 2 diabetes mellitus and ED were included in the study. Patients received vardenafil hydrochloride 20 mg on demand during 12 weeks. At the beginning and 12 weeks after vardenafil administration, plasma samples were collected and analyzed using proteomics. MAIN OUTCOME MEASURES: International Index of Erectile Function-Erectile Function Domain (IIEF-EFD) and plasma protein expression before and after vardenafil administration. Nitrate/nitrite release, PDE5, and soluble guanylate cyclase (sGC) expression and cyclic guanosine monophosphate (cGMP) content in cultured bovine aortic endothelial cells (BAECs). RESULTS: The IIEF-EFD score was markedly improved after 12 weeks of vardenafil administration. Plasma levels of alpha 1-antitrypsin isotypes 4 and 6 and ß-tropomyosin were decreased, whereas apolipoprotein AI isoype 5 was increased 12 weeks after vardenafil administration. Only ß-tropomyosin plasma levels were inversely correlated with IIEF-EFD score. Tropomyosin has been added to cultured BAECs and after 24 hours reduced the protein expression level of sGC-ß1 subunit and decreased the cGMP content. Tropomyosin did not modify PDE5 expression and nitric oxide release in BAECs as compared with control BAECs. Vardenafil (10 µg/mL) did not modify sGC-ß1 subunit expression in tropomyosin + vardenafil-incubated BAECs; however, vardenafil significantly reversed the reduction of cGMP content induced by tropomyosin. CONCLUSION: Vardenafil administration improved erectile functionality in controlled type 2 diabetes mellitus patients with ED, which was associated with reduction of circulating plasma ß-tropomyosin levels. Tropomyosin affected by itself the cGMP generating system suggesting a possible new mechanism involved in ED. Vardenafil reversed the reduction effect of cGMP content elicited by tropomyosin in BAECs.

Dose-response association of physical activity with acute myocardial infarction: do amount and intensity matter?

OBJECTIVE: The aims of this study were to analyze the dose-response association between leisure time physical activity (PA) practice and myocardial infarction (MI), considering not only the total amount but also the amount of PA at different levels of intensity, and to determine whether these associations were modified by age. METHOD: In a population-based age- and sex-matched case-control study, all first acute MI patients aged 25 to 74 years were prospectively registered in four Spanish hospitals between 2002 and 2004. Controls were randomly selected from population-based samples recruited during the same period of time. The Minnesota PA questionnaire was administered to assess total energy expenditure in PA and in light-, moderate-, and high-intensity PA. RESULTS: Finally, 1339 cases and 1339 controls were included. The association between PA and MI likelihood was non-linear, with significantly lower MI odds at low practice levels (≥ 500 MET·min/week), lowest odds around 1500 MET·min/week, and a plateau thereafter. Light- (in subjects older than 64 years), moderate-, and high-intensity PA produced similar benefits. CONCLUSION: Most of the population could reduce their likelihood of MI by engaging in PA at a moderate level of intensity or, in individuals older than 64 years, at a light level of intensity.

Plasma desmoplakin I biomarker of vascular recurrence after ischemic stroke.

Stroke patients have a high risk of vascular recurrence. Biomarkers related to vascular recurrence, however, remain to be identified. The aim of the study was to identify, through proteomic analysis, plasma biomarkers associated with vascular recurrence within one year after the first ischemic stroke. This is a substudy (n = 134) of a large prospective multicenter study of post-stroke patients with an ischemic stroke. Plasma samples were obtained at inclusion. Among the identified proteins, only plasma levels of desmoplakin I were associated with protection against a new vascular event (Odds ratio: 0.64; 95% CI: 0.46-0.89; p = 0.009) after adjustment for hypercholesterolemia, statins and previous atherothrombotic stroke subtype. A greater number of patients without vascular recurrence had been treated with statins within three months of the recent ischemic stroke. Only patients who had been taking statins for 3 months after the ischemic stroke and did not suffer vascular recurrence over a follow-up year, have higher levels of desmoplakin I at the time of inclusion (Odds ratio 0.49; 95% CI: 0.28-0.86; p = 0.013). Increased desmoplakin I levels, determined within 1-3 months of the first ischemic stroke, could be a biomarker for statin responsiveness against a new vascular event in post-ischemic stroke patients taking statins early (1-3 months) after the ischemic stroke.

Atypical Sympathetic Ophthalmia Presenting with Ocular Pain Associated with Posterior Scleral Involvement.

PURPOSE: To describe an atypical case of sympathetic ophthalmia. Design: Case report. RESULTS: A 37 -year-old female presented a 3-day long acute left retroocular pain and photophobia, 1 month after having undergone evisceration of the fellow eye. Upon exploration, the patient presented conjunctival injection, macular retinal folds with peripapillary subretinal fluid, and hypocyanescent choroidal spots on indocyanine green angiography. A sympathetic ophthalmia with a reactive posterior scleritis involvement was diagnosed. The patient underwent treatment with prednisone, mycophenolate, and cyclosporine with slowly tapering, presenting a total recovery over the years. CONCLUSION: Sympathetic ophthalmia may present itself atypically as ocular pain with little vision loss secondarily to a mild panuveitis with reactive scleral involvement.

Proteomic changes related to "bewildered" circulating platelets in the acute coronary syndrome.

Acute coronary syndromes (ACS) are associated with platelet activation. The aim of the present study was to study the protein expression level associated with glycolysis, oxidative stress, cytoskeleton and cell survival in platelets obtained during an ACS. Platelets from 42 coronary ischemic patients, divided into patients admitted within 24 h after the onset of chest pain (ACS group; n=16) and patients with stable coronary ischemic disease (CAD, n=26), were analyzed using proteomics. The expression levels of proteins involved in cellular cytoskeleton (F-actin capping, ß-tubulin, α-tubulin isotypes 1 and 2, vinculin, vimentin and two Ras-related protein Rab-7b isotypes), glycolysis pathway (glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase and two pyruvate kinase isotypes) and cellular-related antioxidant system (manganese superoxide dismutase) and even the expression and activity of glutathione-S-transferase were significantly reduced in platelets from ACS patients compared to CAD patients. Moreover, reduction in the expression of proteins associated with cell survival such as proteasome subunit ß type 1 was also observed in ACS platelets compared with CAD platelets. Principal component and logistic regression analysis suggested the existence of factors (proteins) expressed in the platelets inversely associated with acute coronary ischemia. In summary, these results suggest the existence of circulating antioxidant, cytoskeleton and glycolytic-"bewildered" platelets during the acute phase of a coronary event.

Compression stockings attenuate the expression of proteins associated with vascular damage in human varicose veins.

OBJECTIVE: The objective of this study was to analyze whether compression stocking therapy in the human varicose vein wall may change the levels of biomarkers associated with vein insufficiency. METHODS: Dilated collateral varicose vein samples were obtained from patients showing chronic venous disease (class 2 of the Clinical, Etiology, Anatomy, and Pathophysiology classification). Before elective surgery, 12 patients underwent compression stocking therapy (for 1 month) and 9 patients did not (control group). Expression levels of biomarkers associated with endothelial functionality (nitric oxide synthase 3), inflammation (interleukin-6, interleukin-10), oxidative stress (Gp91phox subunit of NADPH oxidase), and coagulation (factor Xa) were determined. P-selectin, an inflammatory and thrombosis-related biomarker, was also measured. RESULTS: Compression stockings increased the content of nitric oxide synthase 3 (control, 16.48 [16.04-17.40] AU; compression, 83.71 [67.70-91.85] AU; P < .001) in the varicose vein wall that was accompanied by reduction of both interleukin-6 levels (control, 38.72 [33.48-48.52] pg/µg protein; compression, 14.49 [11.05-17.41] pg/µg protein; P = .001) and the expression of Gp91phox subunit of NADPH oxidase (control, 63.24 [53.79-77.03] AU; compression, 36.85 [35.66-52.27] AU; P < .010). P-selectin (control, 77.37 [61.86-85.00] AU; compression, 54.31 [49.60-67.50] AU; P = .017) and factor Xa (control, 90.78 [75.02-100.00] AU; compression, 14.50 [13.77-36.20] AU; P < .001) were also reduced in the varicose vein wall of compression stocking-treated patients. However, P-selectin lost its statistical significance after adjustment by dyslipidemia. CONCLUSIONS: In the varicose vein wall, compression stocking therapy improved the content levels of biomarkers associated with endothelial functionality, inflammation, oxidative stress, and coagulation.

Effects of platelets on the protein expression in aortic segments: A proteomic approach.

It is well known the effects of the vascular wall on platelet activity but little is known about the effects of platelets on the proteins expression in the vascular wall. We analyzed whether platelets may modify the protein expression in the vascular wall. We used an in vitro model coincubating human platelet rich plasma (PRP) with control and 10 ng/ml tumor necrosis factor-α (TNF-α)-preincubated bovine aortic segments. 2DE, mass spectrometry and Western blot analysis were used to determine changes in the expression of proteins associated with the cytoskeleton and energetic metabolism in the aortic segments. In control healthy vascular wall, only the cytoskeleton-related proteins expression was modified by PRP. However, when PRP was coincubated with TNF-α pre-stimulated aortic segments lesser number of cytoskeleton-related proteins were modified. With respect to energetic metabolism, in control segments, PRP failed to modify any of the analyzed energetic-related proteins. However, in TNF-α-preincubated segments the presence of PRP upexpressed glyceraldehyde-3-phosphate dehydrogenase. Moreover, by western blot experiments it was observed that in TNF-α-preincubated segments the expression of fructose 1,6-bisphosphate aldolase was downregulated by platelets. However, no differences were found in the expression of triosephosphate isomerase and ATP synthase α-chain. In addition, the activity of fructose 1,6-bisphosphate aldolase and piruvate content was significantly reduced without modification on triosephosphate isomerase activity. In conclusion, the crosstalk between platelets and vascular wall is bidirectional and platelets regulated in the vascular wall the expression of proteins associated with the cytoskeleton and energetic metabolism, particularly in the healthy vascular wall.

Comparative expression of proteins in left and right atrial appendages from patients with mitral valve disease at sinus rhythm and atrial fibrillation.

INTRODUCTION: The objective was to compare by proteomics the expression of proteins associated with the cytoskeleton, energetic metabolism, and cardiac cytoprotection between left atrial appendages (LAA) and right atrial appendages (RAA) obtained from patients with mitral valve disease both in sinus rhythm (SR, n = 6) and in permanent atrial fibrillation (AF, n = 11). METHODS AND RESULTS: Samples from RAA and LAA were obtained from the same patient. Proteins were separated in 2-dimensional electrophoresis and identified by mass spectrometry. LAA from SR patients upexpressed alpha-actin isotype 1 and desmin isotypes 3 and 5 with respect to RAA. In LAA from AF patients were upexpressed cardiac alpha-actin isotypes 1 and 2, tropomyosin alpha- and beta-chains, and myosin light chain embryonic muscle/atrial isoform with respect to LAA from SR patients. In RAA from AF patients also upexpressed different cytoskeleton associated proteins with respect to RAA from SR patients. Different energetic metabolism-associated proteins were upexpressed in LAA and RAA from AF with respect those from SR patients. In AF patients, the expression of proteins associated with cardiac cytoprotection such as gluthatione-S-transferase, heat shock protein (Hsp) 27, and different Hsp60 isotypes, were higher in RAA but not in LAA with respect to the corresponding appendages in SR patients. CONCLUSIONS: For each individual patient RAA and LAA showed a similar level of proteins expressed associated with cytoskeleton, energetic metabolism, and cardiac cytoprotection. There were more differences in the level of proteins associated with the above-mentioned mechanisms between the atrial appendages from AF with respect to SR patients, which may open new targets for drugs.

Decision tree learning to predict overweight/obesity based on body mass index and gene polymporphisms.

The new technologies for data analysis, such as decision tree learning, may help to predict the risk of developing diseases. The aim of the present work was to develop a pilot decision tree learning to predict overweight/obesity based on the combination of six single nucleotide polymorphisms (SNP) located in feeding-associated genes. Genotype study was performed in 151 healthy individuals, who were anonymized and randomly selected from the TALAVERA study. The decision tree analysis was performed using the R package rpart. The learning process was stopped when 15 or less observation was found in a node. The participant group consisted of 78 men and 73 women, who 100 individuals showed body mass index (BMI) ≥ 25 kg/m2 and 51 BMI < 25 kg/m2. Chi-square analysis revealed that individuals with BMI ≥ 25 kg/m2 showed higher frequency of the allelic variation Ala67Ala in AgRP rs5030980 with respect to those with BMI <25 kg/m2. However, the variant Thr67Ala in AgRP rs5030980 was the most frequently found in individuals with BMI <25 kg/m2. There were no statistical differences in the other analyzed SNPs. Decision tree learning revealed that carriers of the allelic variants AgRP (rs5030980) Ala67Ala, ADRB2 (rs1042714) Gln27Glu or Glu27Glu, INSIG2 (rs7566605) 73 + 9802 with CC or GG genotypes and PPARG (rs1801282) with the allelic variants of Ala12Ala or Pro12Pro, will most likely develop overweight/obesity (BMI ≥ 25 kg/m2). Moreover, the decision tree learning indicated that age and gender may change the developed three decision learning associated with overweight/obesity development. The present work should be considered as a pilot demonstrative study to reinforce the broad field of application of new data analysis technologies, such as decision tree learning, as useful tools for diseases prediction. This technology may achieve a potential applicability in the design of early strategies to prevent overweight/obesity.

Relationship Between Erectile Dysfunction, Diabetes and Dyslipidemia in Hypertensive-Treated Men.

PURPOSE: PRESIDEN study is a large study to analyze the erectile dysfunction (ED) incidence in Spanish population. The present study is a pilot sub-analysis from PRESIDEN to determine if ED or plasma testosterone (TST) level in controlled hypertensive patients may be associated with comorbidities and/or plasma nitrite+nitrate and antioxidant capacity. MATERIALS AND METHODS: Forty-four hypertensive individuals were aleatory selected from PRESIDEN study, matching by age (28 showing ED and 16 without ED). RESULT: Diabetes was present in 28.57% of ED patients and in 18.75% of patients without ED. In patients with and without ED, increasing age showed tendency of higher frequency of an additional comorbidity (diabetes or dyslipemia) (P = .09). Apparently, plasma TST levels were lower in older ED patients compared to younger patients with and without ED, although it did not reach statistical significance (P = .69). Older ED patients also showed lower TST levels than older patients without ED, although it was not statistical significant (16.15 ± 2.84 vs 13.91± 2.77; P = .69). Dyslipidemia was showed by 52.17% with lower TST (? nmol/L) while 23.80% of patients with plasma TST levels > 15 nmol/L had dyslipidemia. The percentage of ED patients was similar between patients with low and high TST levels. CONCLUSION: More ED hypertensive patients seem to show two comorbidities (diabetes and dyslipidemia) than hypertensivepatients without ED. Younger patients with ED tended to show more commonly diabetes than older ED patients. Plasma TST levels were not associated with more prevalence of ED but lower plasma TST levels showed tendency to higher prevalence of dyslipidemia.

Validity Assessment of Low-risk SCORE Function and SCORE Function Calibrated to the Spanish Population in the FRESCO Cohorts.

INTRODUCTION AND OBJECTIVES: To assess the validity of the original low-risk SCORE function without and with high-density lipoprotein cholesterol and SCORE calibrated to the Spanish population. METHODS: Pooled analysis with individual data from 12 Spanish population-based cohort studies. We included 30 919 individuals aged 40 to 64 years with no history of cardiovascular disease at baseline, who were followed up for 10 years for the causes of death included in the SCORE project. The validity of the risk functions was analyzed with the area under the ROC curve (discrimination) and the Hosmer-Lemeshow test (calibration), respectively. RESULTS: Follow-up comprised 286 105 persons/y. Ten-year cardiovascular mortality was 0.6%. The ratio between estimated/observed cases ranged from 9.1, 6.5, and 9.1 in men and 3.3, 1.3, and 1.9 in women with original low-risk SCORE risk function without and with high-density lipoprotein cholesterol and calibrated SCORE, respectively; differences were statistically significant with the Hosmer-Lemeshow test between predicted and observed mortality with SCORE (P < .001 in both sexes and with all functions). The area under the ROC curve with the original SCORE was 0.68 in men and 0.69 in women. CONCLUSIONS: All versions of the SCORE functions available in Spain significantly overestimate the cardiovascular mortality observed in the Spanish population. Despite the acceptable discrimination capacity, prediction of the number of fatal cardiovascular events (calibration) was significantly inaccurate.

Technical modifications for laparoscopic cholecystectomy by the left-handed surgeon.

There is a complete paucity of literature for left-handed surgeons. Some studies revealed that left-handed surgical residents have lesser operating skills and some surgeons have considered leaving surgery at some point in their career owing to laterality-related frustrations. Most important, whereas minimally invasive surgical techniques have had a profound impact on the treatment of diseased gallbladder, these procedures do not eliminate laterality related to the discomfort of left-handed surgeons. Usually, left-handed surgeons must teach themselves a procedure. They must make modifications and learn some technical tips to make a more comfortable, convenient, and safe intervention. The aim of this study was to describe some modifications made by a left-handed surgeon to perform 52 safe laparoscopic cholecystectomies with standard right-handed instruments in our hospital. These surgical steps could be used in a reproducible way to minimize the recurring difficulties of left-handed learners in a surgical residency program.