Fatigue Analysis of NiTi Rotary Endodontic Files through Finite Element Simulation: Effect of Root Canal Geometry on Fatigue Life

This article describes a numerical procedure for estimating the fatigue life of NiTi endodontic rotary files. An enhanced finite element model reproducing the interaction of the endodontic file rotating inside the root canal was developed, which includes important phenomena that allowed increasing the degree of realism of the simulation. A method based on the critical plane approach was proposed for extracting significant strain results from finite element analysis, which were used in combination with the Coffin–Manson relation to predict the fatigue life of the NiTi rotary files. The proposed procedure is illustrated with several numerical examples in which different combinations of endodontic rotary files and root canal geometries were investigated. By using these analyses, the effect of the radius of curvature and the angle of curvature of the root canal on the fatigue life of the rotary files was analysed. The results confirm the significant influence of the root canal geometry on the fatigue life of the NiTi rotary files and reveal the higher importance of the radius of curvature with respect to the angle of curvature of the root canal

Stability of casein micelles cross-linked with genipin: a physicochemical study as a function of pH

Chemical or enzymatic cross-linking of casein micelles (CMs) increases their stability against dissociating agents. In this paper, a comparative study of stability between native CMs and CMs cross-linked with genipin (CMs-GP) as a function of pH is described. Stability to temperature and ethanol were investigated in the pH range 2.0-7.0. The size and the charge ($\zeta$-potential) of the particles were determined by dynamic light scattering. Native CMs precipitated below pH 5.5, CMs-GP precipitated from pH 3.5 to 4.5, whereas no precipitation was observed at pH 2.0-3.0 or pH 4.5-7.0. The isoelectric point of CMs-GP was determined to be pH 3.7. Highest stability against heat and ethanol was observed for CMs-GP at pH 2, where visible coagulation was determined only after 800 s at 140 $^\circ$C or 87.5% (v/v) of ethanol. These results confirmed the hypothesis that cross-linking by GP increased the stability of CMs.Comment: 5 pages, 2 figures, International Dairy Journal, 201

High-Intensity Focused Ultrasound in Small Renal Masses

High-intensity focused ultrasound (HIFU) competes with radiofrequency and cryotherapy for the treatment of small renal masses as a third option among ablative approaches. As an emerging technique, its possible percutaneous or laparoscopic application, low discomfort to the patient and the absence of complications make this technology attractive for the management of small renal masses. This manuscript will focus on the principles, basic research and clinical applications of HIFU in small renal masses, reviewing the present literature. Therapeutic results are controversial and from an clinical view, HIFU must be considered a technique under investigation at present time. Further research is needed to settle its real indications in the management of small renal masses; maybe technical improvements will certainly facilitate its use in the management of small renal masses in the near future

Estudio del efecto de CES (2-cloroetil-sulfuro) y quercetina en fibroblastos humanos

El gas mostaza es un agente tóxico sintético que se utilizó el siglo pasado con fines bélicos. Se trata de una sustancia vesicante, ya que se absorbe principalmente por la piel produciendo ampollas, edema, irritación, ulceraciones y quemaduras. También puede absorberse por vía ocular (conjuntiva) y vía respiratoria. Su principal mecanismo de acción es la alquilación de diversos componentes celulares, incluido el ADN. Su intervención en mecanismos inflamatorios produce la liberación de especies reactivas de oxígeno que provocan mutaciones en el ADN, alterando la división celular y en última instancia causando la muerte celular. En este estudio se ha trabajado con fibroblastos humanos cultivados en medio DMEM (Dulbecco´s Modified Eagle´s Medium) y con uno de sus derivados, el sulfuro de mostaza con fórmula química 2-cloroetil- sulfuro (CES), para determinar la viabilidad celular tras una exposición de 30 minutos a diferentes concentraciones de CES (200, 500, 1000 y 2000 µM). Se ha calculado que la dosis letal al 50% (LD50) se encuentra cercana a 1000 µM mediante el uso de la técnica MTT (Thiazolyl Blue Tetrazolium). A través de la citometría de imagen AMNIS hemos podido diferenciar los diferentes tipos de muerte celular (necrosis, necroptosis, apoptosis temprana, apoptosis tardía) que produce el sulfuro de mostaza a la concentración LD50 de 1000 µM Se ha comprobado por primera vez el efecto protector que ofrece el radical libre quercetina frente a la toxicidad celular que causa el sulfuro de mostaza. Este estudio ha utilizado concentraciones de quercetina de 0.5 y 2.5 µM en fibroblastos expuestos a sulfuro de mostaza a 1000 µM, habiéndose obtenido una protección celular del 66,22 y 88,96% respectivamente

Efecto de la suplementación con granos secos de destilería (DDGS) sobre los parámetros de la fermentación ruminal in situ en vacunos pastoreando sorgo forrajero (Sorghum spp)

Aim. To evaluate the effect of supplementation with distillers dried grains (DDGS) on in situ ruminal fermentation parameters by cattle grazing on forage sorghum. Materials and methods: Four Hereford heifers (793 ± 73 kg live weight) using a ruminal cannula, grazing on forage sorghum, with day-in enclosure and artificial shade, were part of a randomized crossover design study with two treatments: without supplementation (WOS) and with supplementation (WS), fed on DDGS. The experimental design comprised two 14-day periods (10 days for diet transition, and 4 days for measurements). Results: Supplementation did not affect DM consumption (P > 0.05), though it increased total consumption (P < 0.05). The WS treatment caused lower ruminal pH (6.17 vs. 6.55; (P < 0.05), and greater N_NH4 concentration (P < 0.05). The effective degradability of DM was 51.25%, the same as the other treatment (P > 0.05), whereas the effective NDF was lower in the WS treatment (P < 0.05). DM digestibility in WS was lower (65.75 vs. 60.75%), whereas NDF digestibility was 68.50 vs. 62.50%. Conclusion: DDGS supplementation decreased ruminal pH and raised N_NH4 concentrations, reducing the fiber’s effective degradability of DM and NDF. Keywords: DDGS, heifers, supplementation (Source: AGROVOC)Objetivo. Evaluar el efecto de la suplementación con granos secos de destilería más solubles (DDGS) sobre los parámetros de la fermentación ruminal in situ en vacunos pastoreando sorgo forrajero. Materiales y métodos: Cuatro novillos Hereford (793 ± 73 kg peso vivo) provistos de cánula ruminal pastoreando sorgo forrajero con encierro diurno y sombra artificial fueron asignados al azar en diseño crossover a dos tratamientos: sin suplemento (SS) y suplementados (CS), con DDGS. El diseño experimental comprendió dos períodos de 14 días (10 transición entre dietas; 4 de mediciones). Resultados: La suplementación no afectó el consumo de MS de forraje (P > 0,05), pero sí aumentó el consumo total (P < 0,05). El tratamiento CS presentó menor pH ruminal (6,17 vs. 6,55; (P < 0,05) y mayor concentración N_NH4 (P < 0,05). La degradabilidad efectiva de la MS fue 51,25% sin diferencias entre tratamientos (P > 0,05), mientras que la degradabilidad efectiva de la FDN fue menor CS (P < 0,05). La digestibilidad de la MS (65,75 vs 60,75%) y de la FDN (68,50 vs 62,50%) fue menor CS. Conclusión: La suplementación con DDGS disminuyó el pH ruminal y aumentó las concentraciones de N_NH4, disminuyendo la degradabilidad efectiva de la fibra y la digestibilidad de la MS y FDN. Palabras clave: DDGS, novillos, suplementación (Fuente: AGROVOC

Cyclooxygenase-2 polymorphisms confer susceptibility to sarcoidosis but are not related to prognosis

SummaryBackgroundThe aim of this multicenter study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of the cyclooxygenase-2 (COX2) gene and susceptibility to sarcoidosis, as well as the relation between these SNPs and the evolution of the disease.Material and methodsThis multicenter investigation involved seven hospitals in Spain. We used a case–control design followed by a prospective follow-up study. Sarcoid patients were recruited from the participating institutions during outpatient routine visits. Age- and gender-matched control subjects were recruited mainly from among outpatients attending the participating hospitals. Four SNPs in the COX2 gene (COX2.5909 T > G, COX2.8473 T > C, COX2.926 G > C, and COX2.3050 G > C) were genotyped using fluorescent hybridization probes among 131 patients with sarcoidosis (63 males; mean age: 47 ± 15 years) and 157 healthy controls (83 males; mean age: 50 ± 16 years). We employed a binomial multiple logistic regression analysis to test the association between the selected SNPs and disease susceptibility. The clinical, functional and radiological prognosis of the sarcoidosis patients was determined after a mean follow-up of 37.4 ± 30.4 months.ResultsCarriers of the homozygous CC genotype of the COX2.8473 T > C polymorphism had a higher risk of sarcoidosis compared with TT carriers (OR: 3.08; 95% CI: 1.2–7.7; p = 0.035). 84% of patients achieved improvement or complete remission at follow-up. No association between the investigated SNPs and prognosis was seen.ConclusionsOur data suggest that the homozygous CC genotype of the COX2.8473 T > C polymorphism may be associated with sarcoidosis susceptibility. No significant association with prognosis was detected

The effect of physical activity on mortality and cardiovascular disease in 130 000 people from 17 high-income, middle-income, and low-income countries:the PURE study

BACKGROUND: Physical activity has a protective effect against cardiovascular disease (CVD) in high-income countries, where physical activity is mainly recreational, but it is not known if this is also observed in lower-income countries, where physical activity is mainly non-recreational. We examined whether different amounts and types of physical activity are associated with lower mortality and CVD in countries at different economic levels. METHODS: In this prospective cohort study, we recruited participants from 17 countries (Canada, Sweden, United Arab Emirates, Argentina, Brazil, Chile, Poland, Turkey, Malaysia, South Africa, China, Colombia, Iran, Bangladesh, India, Pakistan, and Zimbabwe). Within each country, urban and rural areas in and around selected cities and towns were identified to reflect the geographical diversity. Within these communities, we invited individuals aged between 35 and 70 years who intended to live at their current address for at least another 4 years. Total physical activity was assessed using the International Physical Activity Questionnaire (IPQA). Participants with pre-existing CVD were excluded from the analyses. Mortality and CVD were recorded during a mean of 6·9 years of follow-up. Primary clinical outcomes during follow-up were mortality plus major CVD (CVD mortality, incident myocardial infarction, stroke, or heart failure), either as a composite or separately. The effects of physical activity on mortality and CVD were adjusted for sociodemographic factors and other risk factors taking into account household, community, and country clustering. FINDINGS: Between Jan 1, 2003, and Dec 31, 2010, 168 916 participants were enrolled, of whom 141 945 completed the IPAQ. Analyses were limited to the 130 843 participants without pre-existing CVD. Compared with low physical activity (\u3c600 metabolic equivalents [MET] × minutes per week or \u3c150 minutes per week of moderate intensity physical activity), moderate (600-3000 MET × minutes or 150-750 minutes per week) and high physical activity (\u3e3000 MET × minutes or \u3e750 minutes per week) were associated with graded reduction in mortality (hazard ratio 0·80, 95% CI 0·74-0·87 and 0·65, 0·60-0·71; p\u3c0·0001 for trend), and major CVD (0·86, 0·78-0·93; p\u3c0·001 for trend). Higher physical activity was associated with lower risk of CVD and mortality in high-income, middle-income, and low-income countries. The adjusted population attributable fraction for not meeting the physical activity guidelines was 8·0% for mortality and 4·6% for major CVD, and for not meeting high physical activity was 13·0% for mortality and 9·5% for major CVD. Both recreational and non-recreational physical activity were associated with benefits. INTERPRETATION: Higher recreational and non-recreational physical activity was associated with a lower risk of mortality and CVD events in individuals from low-income, middle-income, and high-income countries. Increasing physical activity is a simple, widely applicable, low cost global strategy that could reduce deaths and CVD in middle age. FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Ontario SPOR Support Unit, Ontario Ministry of Health and Long-Term Care, AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, GSK, Novartis, King Pharma, and national and local organisations in participating countries that are listed at the end of the Article

Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n = 3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (pcombined  = 5.66 × 10-5 ; ORcombined  = 2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (pcombined  = 1.02 × 10-4 ; ORcombined  = 2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10DmRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p = 0.01 and p < 0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p = 0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC.This work was supported by the Spanish Society of Medical Oncology; Fundación SEOM and Fundación Salud 2000; and Government of Navarra.S

Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n=3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (p(combined)=5.66x10(-5); ORcombined=2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p(combined)=1.02x10(-4); ORcombined=2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10D mRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p=0.01 and p<0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p=0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC