Myocardial Perfusion in Rheumatoid Arthritis Patients: Associations with Traditional Risk Factors and Novel Biomarkers

Introduction. Cardiovascular (CV) diseases are a major cause of death in rheumatoid arthritis (RA) patients. Novel biomarkers [B-type natriuretic peptide (BNP); osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL) ratio; and dickkopf-1 (DKK-1)] have been used in CV risk assessment. We analysed, in established RA patients, the presence of silent myocardial ischemia and its association with clinical variables, BNP, and bone and atheroma biomarkers. Methods. From a single-center tertiary referral hospital, RA patients asymptomatic for CV disease were submitted to myocardial perfusion scintigraphy (MPS) under adenosine stress and biomarkers measurements. Logistic regression was used to estimate crude odds ratios (OR) and 95% confidence intervals (CI). Results. In 189 patients, perfusion defects were frequent (25%) and associated with BNP ≥ 100 pg/mL (OR = 5.68; 95% CI: 2.038–15.830), fourth log OPG/RANKL ratio quartile (OR = 2.88; 95% CI: 1.091–7.622), and DKK-1 ≥ 133 pmol/L (OR = 2.69; 95% CI: 1.058–6.840). Similar associations were confirmed in those with C-reactive protein > or ≤ 3 mg/L. No relationship was found with the majority of traditional CV factors nor with disease variables. Conclusions. Our results corroborated the hypothesis that MPS could reveal subclinical CV dysfunction, supported the utility of BNP measurements as a screening tool, and put in perspective the potential usefulness of complementary approaches in CV risk assessment in RA patients

The Effect of Transposable Element Insertions on Gene Expression Evolution in Rodents

Background:Many genomes contain a substantial number of transposable elements (TEs), a few of which are known to be involved in regulating gene expression. However, recent observations suggest that TEs may have played a very important role in the evolution of gene expression because many conserved non-genic sequences, some of which are know to be involved in gene regulation, resemble TEs. Results:Here we investigate whether new TE insertions affect gene expression profiles by testing whether gene expression divergence between mouse and rat is correlated to the numbers of new transposable elements inserted near genes. We show that expression divergence is significantly correlated to the number of new LTR and SINE elements, but not to the numbers of LINEs. We also show that expression divergence is not significantly correlated to the numbers of ancestral TEs in most cases, which suggests that the correlations between expression divergence and the numbers of new TEs are causal in nature. We quantify the effect and estimate that TE insertion has accounted for ~20% (95% confidence interval: 12% to 26%) of all expression profile divergence in rodents. Conclusions:We conclude that TE insertions may have had a major impact on the evolution of gene expression levels in rodents

Vascular health in patients in remission of Cushing's syndrome is comparable to that in BMI-matched controls.

CONTEXT: In active Cushing's syndrome (CS), patients suffer from endothelial dysfunction and premature atherosclerosis. However, it is uncertain to what extent vascular health recovers after long-term remission. This is highly relevant as this topic relates to future development of cardiovascular disease. OBJECTIVE: To investigate whether micro- and macrovascular health is impaired after long-term remission of CS, in patients with no or adequately treated co-morbidities. DESIGN AND SETTING: Cross-sectional case-control study in two tertiary referral centers. PATIENTS AND MAIN OUTCOME MEASURES: 63 patients (remission of CS for ≥ 4 years) and 63 healthy, well-matched controls were compared. In group A (58 patients and 58 controls) serum biomarkers associated with endothelial dysfunction, intima media thickness, pulse wave velocity and pulse wave analysis were studied. In group B (14 patients and 14 controls) endothelium-dependent and-independent vasodilatation was studied in conduit arteries (flow mediated dilation of the brachial artery) and forearm skeletal muscle resistance arteries (vasodilator response to intra-arterial acetylcholine, sodium-nitroprusside and N(G)-monomethyl-L-arginine using venous occlusion plethysmography). RESULTS: There were no significant differences between the outcome measures of vascular health of patients and controls in group A and B. CONCLUSION: Vascular health of patients in long-term remission of Cushing's syndrome seems to be comparable to that of healthy gender-, age and BMI matched controls, provided that the patients have no, or adequately controlled co-morbidities. Therefore, the effects of hypercortisolism per se on the vasculature may be reversible. This accentuates the need for stringent treatment of metabolic co-morbidities in these patients

Detection and Antimicrobial Resistance Profile of Enteropathogenic (EPEC) and Shigatoxigenic Escherichia coli (STEC) in Conventional and Organic Broiler Chickens

ABSTRACT Enteropatogenic Escherichia coli (EPEC) and shigatoxigenic E. coli (STEC), are generally poultry and poultry product isolate and can cause serious human infections. Many strains may become resistant to various antimicrobials, which can hinder the treatment of bacterial diseases. Organic farming seeks to avoid the selection and frequency of antimicrobial-resistant bacteria. This study aims to verify the resistance of EPEC and STEC from organic and conventional (industrial) broiler isolates to antimicrobials. All isolates were submitted to disk diffusion test with tetracycline, gentamicin, enrofloxacin, ceftriaxone and amoxicillin + clavulanate (TET, GEN, ENO, CTX, AMC) and PCR to detect specific virulence genes for EPEC and STEC. A total of 297 E. coli strains were isolated, 213 from conventional. In organic broiler, 84 strains were isolated. The strains from the conventional broiler isolates were resistant to five antimicrobials tested: TET 48.82% (104/213), ENO 28.17% (60/213), CTX 15.49% (33/213), GEN 14.55% (31/213), and AMC 7.04% (15/213), and 9.86% (21/213) were considered multidrug-resistant. Organic chicken strains were resistant to four of the antimicrobials tested: TET 35.7% (30/84), ENO 9.5% (8/84), CTX 2.4% (2/84), GEN 4.8% (4/84). Of the strains from the organic broiler chicken isolates, only 1.2% (1/84) was considered multidrug-resistant. No EPEC and STEC were found in the organic chicken samples. The multidrug resistance was characterized in 9.52% (2/21) of the EPEC and 4.76% (1/21) of the STEC. The study demonstrated the absence of EPEC and STEC strains in organic broilers and carcasses and a lower frequency of multiresistant strains compared to conventional breeding

Cosmology of a Scalar Field Coupled to Matter and an Isotropy-Violating Maxwell Field

Motivated by the couplings of the dilaton in four-dimensional effective actions, we investigate the cosmological consequences of a scalar field coupled both to matter and a Maxwell-type vector field. The vector field has a background isotropy-violating component. New anisotropic scaling solutions which can be responsible for the matter and dark energy dominated epochs are identified and explored. For a large parameter region the universe expands almost isotropically. Using that the CMB quadrupole is extremely sensitive to shear, we constrain the ratio of the matter coupling to the vector coupling to be less than 10^(-5). Moreover, we identify a large parameter region, corresponding to a strong vector coupling regime, yielding exciting and viable cosmologies close to the LCDM limit.Comment: Refs. added, some clarifications. Published in JHEP10(2012)06

Simultaneous saccharification and fermentation of hydrothermal pretreated lignocellulosic biomass: evaluation of process performance under multiple stress conditions

Industrial lignocellulosic bioethanol processes are exposed to different environmental stresses (such as inhibitor compounds, high temperature, and high solid loadings). In this study, a systematic approach was followed where the liquid and solid fractions were mixed to evaluate the influence of varied solid loadings, and different percentages of liquor were used as liquid fraction to determine inhibitor effect. Ethanol production by simultaneous saccharification and fermentation (SSF) of hydrothermally pretreated Eucalyptus globulus wood (EGW) was studied under combined diverse stress operating conditions (3038 °C, 6080 g of liquor from hydrothermal treatment or autohydrolysis (containing inhibitor compounds)/100 g of liquid and liquid to solid ratio between 4 and 6.4 g liquid in SSF/g unwashed pretreated EGW) using an industrial Saccharomyces cerevisiae strain supplemented with low-cost byproducts derived from agro-food industry. Evaluation of these variables revealed that the combination of temperature and higher solid loadings was the most significant variable affecting final ethanol concentration and cellulose to ethanol conversion, whereas solid and autohydrolysis liquor loadings had the most significant impact on ethanol productivity. After optimization, an ethanol concentration of 54 g/L (corresponding to 85 % of conversion and 0.51 g/Lh of productivity at 96 h) was obtained at 37 °C using 60 % of autohydrolysis liquor and 16 % solid loading (liquid to solid ratio of 6.4 g/g). The selection of a suitable strain along with nutritional supplementation enabled to produce noticeable ethanol titers in quite restrictive SSF operating conditions, which can reduce operating cost and boost the economic feasibility of lignocellulose-to-ethanol processes.The authors thank the financial support from the Strategic Project of UID/BIO/04469/2013 CEB Unit and A Romaní postdoctoral grant funded by Xunta of Galicia (Plan I2C, 2014)

Correlation between endometrial dating of luteal phase days 6 and 10 of the same menstrual cycle

CONTEXT: Endometrial maturation, important in the diagnosis of infertile couples, has been evaluated since 1950 using the Noyes criteria. Nevertheless, there is no consensus regarding the most suitable period of the luteal phase for performing the biopsy. OBJETIVE: This study evaluated the correlation between the histological dating of two endometrial biopsies performed in the same menstrual cycle, on luteal phase days six and ten.DESIGN: Prospective study. SETTING: Human Reproduction Division of the Federal University of São Paulo, referral center. PATIENTS:Twenty-five women complaining of infertility had their menstrual cycles monitored by ultrasound and LH plasma levels, to obtain evidence of ovulation. PROCEDURES: Endometrial biopsies were performed on luteal phase days LH+6 and LH+10 (luteal phase day 1 = LH+1 = the day that follows LH peak). Dating was done according to morphometric criteria, in which an endometrium sample is considered out of phase if the minimum maturation delay is one day. On day LH+6, blood was drawn for plasma progesterone level determination. RESULTS: All patients had an ovulatory cycle (mean LH peak: 47.4 U/L; mean follicular diameter on LH peak day: 18.9 mm; mean endometrial thickness on LH peak day: 10.3 mm; mean plasma progesterone level on day LH+6: 14.4 ng/ml). 14 patients had both biopsies in phase; 5 patients had out of phase biopsies only on day LH+6; 3 had out of phase biopsies only on day LH+10 and 3 patients had out of phase biopsies on both days. McNemar's test showed no statistical difference between these data (p>33.36%). CONCLUSIONS: The correlation found between the endometrial datings suggests that biopsies performed on either of these two days are suitable for evaluation of endometrial maturation.CONTEXTO: A verificação da maturidade endometrial, elemento diagnóstico necessário na avaliação do casal com queixa de infertilidade, vem sendo feita desde 1950 através do critério de datação histológica de Noyes. No entanto, não existe um consenso em relação ao período da fase lútea mais adequado para a colheita. OBJETIVO: Avaliar a correlação entre as datações histológicas de duas amostras de endométrio colhidas nos dias 6 e 10 da fase lútea de um mesmo ciclo menstrual. LOCAL: Setor de Reprodução Humana da Universidade Federal de São Paulo (UNIFESP). TIPO DE ESTUDO: Estudo prospectivo. Constou da comparação entre duas datações de endométrio num mesmo ciclo menstrual. PARTICIPANTES: 25 pacientes com queixa de infertilidade tiveram um ciclo menstrual monitorizado por ultra-sonografia e medida plasmática de LH, para demonstração de ovulação. PROCEDIMENTO: Biópsias de endométrio foram feitas nos dias LH+6 e LH+10 da fase lútea, considerando-se o dia seguinte ao do pico de LH como LH+1. A datação foi feita de acordo com critério morfométrico, considerando-se o endométrio como fora de fase, se o atraso de maturação mínimo fosse de um dia. No dia LH+6 foi feita dosagem de progesterona plasmática. RESULTADOS: Todas as pacientes apresentaram ciclos ovulatórios (média dos valores de pico de LH: 47,3 U/L; média dos diâmetros foliculares no dia do pico de LH: 18,9 mm; média das espessuras do endométrio no dia do pico de LH: 10,3 mm; média das concentrações de progesterona plasmática no dia LH+6: 14,4 ng/ml.). Em 14 pacientes, as duas biópsias estavam em fase. Houve atraso de maturação apenas no dia LH+6 em cinco pacientes; apenas no dia LH+10 em três pacientes e, nos dois dias, em três pacientes. Não houve diferença estatística entre esses valores (teste de McNemar, p=33,36%). CONCLUSÕES: Os resultados sugerem que a colheita do endométrio em qualquer dos dias (sexto ou décimo) da fase lútea fornece resultados semelhantes em relação à maturidade endometrial.Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Neonatal anthropometry: a tool to evaluate the nutritional status and predict early and late risks

Neonatal anthropometry is an inexpensive, noninvasive and convenient tool for bedside evaluation, especially in sick and fragile neonates. Anthropometry can be used in neonates as a tool for several purposes: diagnosis of foetal malnutrition and prediction of early postnatal complications; postnatal assessment of growth, body composition and nutritional status; prediction of long-term complications including metabolic syndrome; assessment of dysmorphology; and estimation of body surface. However, in this age group anthropometry has been notorious for its inaccuracy and the main concern is to make validated indices available. Direct measurements, such as body weight, length and body circumferences are the most commonly used measurements for nutritional assessment in clinical practice and in field studies. Body weight is the most reliable anthropometric measurement and therefore is often used alone in the assessment of the nutritional status, despite not reflecting body composition. Derived indices from direct measurements have been proposed to improve the accuracy of anthropometry. Equations based on body weight and length, mid-arm circumference/head circumference ratio, and upper-arm cross-sectional areas are among the most used derived indices to assess nutritional status and body proportionality, even though these indices require further validation for the estimation of body composition in neonates

Cocoa flavanols adjuvant to an oral nutritional supplement acutely enhances nutritive flow in skeletal muscle without altering leg glucose uptake kinetics in older adults

This is the final version. Available on open access from MDPI via the DOI in this record. Data Availability Statement: The data presented in this study are available on request from the corresponding authors.Ageing is associated with postprandial muscle vascular and metabolic dysfunction, suggesting vascular modifying interventions may be of benefit. Reflecting this, we investigated the impact of acute cocoa flavanol (450–500 mg) intake (versus placebo control) on vascular (via ultrasound) and glucose/insulin metabolic responses (via arterialised/venous blood samples and ELISA) to an oral nutritional supplement (ONS) in twelve healthy older adults (50% male, 72 ± 4 years), in a crossover design study. The cocoa condition displayed significant increases in m. vastus lateralis microvascular blood volume (MBV) in response to feeding at 180 and 240-min after ONS consumption (baseline: 1.00 vs. 180 min: 1.09 ± 0.03, p = 0.05; 240 min: 1.13 ± 0.04, p = 0.002), with MBV at these timepoints significantly higher than in the control condition (p 0.05). Similarly, glucose uptake and insulin increased in response to ONS (p 0.05). Thus, acute cocoa flavanol supplementation can potentiate oral feeding-induced increases in MBV in older adults, but this improvement does not relay to muscle glucose uptake.Abbott NutritionMedical Research Council (MRC)National Institute for Health Research (NIHR