Disease-modifying antirheumatic drugs are associated with a reduced risk for cardiovascular disease in patients with rheumatoid arthritis: a case control study

Rheumatoid arthritis (RA) is characterized by inflammation and an increased risk for cardiovascular disease (CVD). This study investigates possible associations between CVD and the use of conventional disease-modifying antirheumatic drugs (DMARDs) in RA. Using a case control design, 613 RA patients (5,649 patient-years) were studied, 72 with CVD and 541 without CVD. Data on RA, CVD and drug treatment were evaluated from time of RA diagnosis up to the first cardiovascular event or the end of the follow-up period. The dataset was categorized according to DMARD use: sulfasalazine (SSZ), hydroxychloroquine (HCQ) or methotrexate (MTX). Odds ratios (ORs) for CVD, corrected for age, gender, smoking and RA duration, were calculated per DMARD group. Patients who never used SSZ, HCQ or MTX were used as a reference group. MTX treatment was associated with a significant CVD risk reduction, with ORs (95% CI): 'MTX only', 0.16 (0.04 to 0.66); 'MTX and SSZ ever', 0.20 (0.08 to 0.51); and 'MTX, SSZ and HCQ ever', 0.20 (0.08 to 0.54). The risk reductions remained significant after additional correction for the presence of rheumatoid factor and erosions. After correction for hypertension, diabetes and hypercholesterolemia, 'MTX or SSZ ever' and 'MTX, SSZ and HCQ ever' showed significant CVD risk reduction. Rheumatoid factor positivity and erosions both increased CVD risk, with ORs of 2.04 (1.02 to 4.07) and 2.36 (0.92 to 6.08), respectively. MTX and, to a lesser extent, SSZ were associated with significantly lower CVD risk compared to RA patients who never used SSZ, HCQ or MTX. We hypothesize that DMARD use, in particular MTX use, results in powerful suppression of inflammation, thereby reducing the development of atherosclerosis and subsequently clinically overt CVD.     

Biological, nutritional, and histochemical basis for improving an artificial diet for Bracon hebetor Say (Hymenoptera: Braconidae)

The biology of Bracon hebetor Say (Hymenoptera: Braconidae) reared on fifth instars of Anagasta kuehniella (Zeller) (Lepidoptera: Pyralidae) (natural diet) and in vitro (artificial diet) was evaluated. Data on the number of instars, development time and food intake were collected, and histochemical tests were conducted to detect proteins and lipids in the parasitoid's digestive tract. The data disclosed differences that can help to improve artificial rearing of B. hebetor. B. hebetor had three instars in both diets, but the developmental time on the artificial diets was prolonged due to the increase in larval and pupal development times. Larvae grew faster on the natural host and required a lower food intake (2.7 microl) as compared to that required by the larvae feeding on the artificial diet (3.8 microl). Analysis of diet protein content and host hemolymph and the observations on the parasitoid larvae gut content indicated altogether the artificial diets requires the addition of others sources of proteins and lipids to improve the overall nutrition quality of the in vitro rearing system for this ectoparasitoid.     

Effect of kosmotropicity of ionic liquids on the enzyme stability in aqueous solutions

This paper examined the effect of several pyridinium and imidazolium-based ionic liquids (ILs) on the protease stability in aqueous solutions. In general, the enzyme was found quite active at low concentrations of hydrophilic ILs. In aqueous environment, the enzyme was stabilized by the kosmotropic anions (such as CF3COO- and CH3COO-) and chaotropic cations (such as [BuPy]+ and [EMIM]+), but was destabilized by chaotropic anions (such as tosylate and BF4-) and kosmotropic cations (such as [BMIM]+).     

Protection status as determinant of carbon stock drivers in Cerrado sensu stricto

天然植被在全球碳循环和碳储存中扮演着重要角色。巴西大草原塞拉多保护区(Cerrado)因自身固有特性被认为是一个碳汇。本研究的目的是评估具有不同保护状况的三个地区,控制区(法定保护区)、保护区(PA)和非保护区(Non-PA)地上生物量与生物多样性关系的变化。这三个被研究的地区都位于巴西米纳斯吉拉斯州(Minas Gerais)北部。根据森林清查资料,该研究对地上碳储量进行了估算,并测量了每个地区生物多样性指标的三个维度：功能性状优势度、分类学多样性和功能多样性。对物种的以下功能性状进行了评价：木材密度、最大直径和种子大小。通过建立广义线性模型,评估了碳储量、群落加权平均值、物种丰富度和多样性以及功能多样性指数在不同地区间的差异。 研究结果表明,未受保护的地区碳储量、物种丰富度、物种多样性、功能丰富度和功能分散度均较低,而保护区和非保护区群落加权平均值最大直径和种子大小均低于法定保护区。广义线性模型结果表明,碳储量与物种和功能丰富度指数在同一地区内和不同地区间存在相关性,因此,物种丰富度可以作为功能丰富度和碳储量的替代指标。物种丰富度和群落加权平均值最大直径对碳储量有正向影响,功能分散度对碳储量有负向影响。功能丰富度、物种多样性和群落加权平均值种子大小出现在最佳模型中,但对碳储量没有显著的直接影响。因此,我们的结论是,在缺乏保护的巴西塞拉多地区会降低物种丰富度和碳储量。     

Trade-offs between ontogenetic changes and food consumption in Brazilian silverside Atherinella brasiliensis from two tropical estuaries

Salinity variation in estuarine environments influences the distribution of fish species as well as the availability of food resources to be used by them. This study examines the effect of the range of salinity on the trade-off between growth and feeding intensity of Atherinella brasiliensis from two tropical estuaries (positive and hypersaline). To investigate the effects of salinity, we hypothesized that hypersalinity negatively affects foraging intensity, consumption and prey selection by the Brazilian silverside, leading to differences in body condition. Sampling was carried out using the beach seine method in two areas of the estuaries (upper and lower zone) during rainy and dry periods. A total of 2549 stomachs (1124 for the positive estuary and 1425 for the hypersaline estuary) were examined, and the results indicated a dissimilarity of 92.7% of the diet between environments. In the positive estuary, there was more predation on Calanoida, Gastropoda, Hymenoptera, Ceratopogonidae larvae and Decapoda larvae, while Alga and plant-material characterized the diet in the hypersaline estuary. Significant correlations between the volume of food and salinity were observed in both estuaries. The vacuity index indicated that hypersaline environments presented higher contributions of semifull stomachs, indicating an intense consumption of algae. On the other hand,in the positive estuary, these values were less intense, but the stomachs were always with animal items. The variation found for both environments reinforces the effect of salinity on the physiological mechanism of the populations once the higher proportions of filled stomachs in the hypersaline environment indicate the need for constant and high ingestion of prey to guarantee the pronounced energy expenditure with osmoregulation.     

Cognitive and Surgical Outcome in Mesial Temporal Lobe Epilepsy Associated with Hippocampal Sclerosis Plus Neurocysticercosis: A Cohort Study

Background

Where neurocysticercosis (NCC) is endemic, chronic calcified neurocysticercosis (cNCC) can be observed in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS). Considering that both disorders cause recurrent seizures or cognitive impairment, we evaluated if temporal lobectomy is cognitively safe and effective for seizure control in MTLE-HS plus cNCC.

Methods

Retrospective cohort study of neuropsychological profile and surgical outcome of 324 MTLE-HS patients submitted to temporal lobectomy, comparing the results according to the presence or absence of cNCC.

Findings

cNCC occurred in 126 (38.9%) of our MTLE-HS patients, a frequency higher than expected, more frequently in women than in men (O.R. = 1.66; 95% C.I. = 1.05–2.61; p = 0.03). Left-side (but not right side) surgery caused impairment in selected neuropsychological tests, but this impairment was not accentuated by the presence of cNCC. Ninety-four (74.6%) patients with MTLE-HS plus cNCC and 153 patients (77.3%) with MTLE-HS alone were Engel class I after surgery (O.R. = 1.16; 95% C.I. = 0.69–1.95; p = 0.58). However, the chances of Engel class IA were significantly lower in MTLE-HS plus cNCC than in patients with MTLE-HS alone (31.7% versus 48.5%; O.R. = 2.02; 95% C.I. = 1.27–3.23; p = 0.003). Patients with MTLE-HS plus cNCC showed higher rates of Engel class ID (15.1% versus 6.6%; O.R. = 2.50; 95% C.I. = 1.20–5.32; p = 0.012).

Interpretation

cNCC can be highly prevalent among MTLE-HS patients living in areas where neurocysticercosis is endemic, suggesting a cause-effect relationship between the two diseases. cNCC does not add further risk for cognitive decline after surgery in MTLE-HS patients. The rates of Engel class I outcome were very similar for the two groups; however, MTLE-HS plus cNCC patients achieved Engel IA status less frequently, and Engel ID status more frequently. Temporal lobectomy can be safely performed in most patients with MTLE-HS plus cNCC without affecting cognitive outcome. Long-term surgical seizure control in MTLE-HS plus cNCC is still satisfactory, as long as selected patients remain under medication.     

To Investigate the Necessity of STRA6 Upregulation in T Cells during T Cell Immune Responses

Our earlier study revealed that STRA6 (stimulated by retinoic acid gene 6) was up-regulated within 3 h of TCR stimulation. STRA6 is the high-affinity receptor for plasma retinol-binding protein (RBP) and mediates cellular vitamin A uptake. We generated STRA6 knockout (KO) mice to assess whether such up-regulation was critical for T-cell activation, differentiation and function. STRA6 KO mice under vitamin A sufficient conditions were fertile without apparent anomalies upon visual inspection. The size, cellularity and lymphocyte subpopulations of STRA6 KO thymus and spleen were comparable to those of their wild type (WT) controls. KO and WT T cells were similar in terms of TCR-stimulated proliferation in vitro and homeostatic expansion in vivo. Naive KO CD4 cells differentiated in vitro into Th1, Th2, Th17 as well as regulatory T cells in an analogous manner as their WT counterparts. In vivo experiments revealed that anti-viral immune responses to lymphocytic choriomeningitis virus in KO mice were comparable to those of WT controls. We also demonstrated that STRA6 KO and WT mice had similar glucose tolerance. Total vitamin A levels are dramatically lower in the eyes of KO mice as compared to those of WT mice, but the levels in other organs were not significantly affected after STRA6 deletion under vitamin A sufficient conditions, indicating that the eye is the mouse organ most sensitive to the loss of STRA6.Our results demonstrate that 1) in vitamin A sufficiency, the deletion of STRA6 in T cells does no affect the T-cell immune responses so-far tested, including those depend on STAT5 signaling; 2) STRA6-independent vitamin A uptake compensated the lack of STRA6 in lymphoid organs under vitamin A sufficient conditions in mice; 3) STRA6 is critical for vitamin A uptake in the eyes even in vitamin A sufficiency.     

Efnb1 and Efnb2 proteins regulate thymocyte development, peripheral T cell differentiation, and antiviral immune responses and are essential for interleukin-6 (IL-6) signaling

Erythropoietin-producing hepatocellular kinases (Eph kinases) constitute the largest family of cell membrane receptor tyrosine kinases, and their ligand ephrins are also cell surface molecules. Because of promiscuous interaction between Ephs and ephrins, there is considerable redundancy in this system, reflecting the essential roles of these molecules in the biological system through evolution. In this study, both Efnb1 and Efnb2 were null-mutated in the T cell compartment of mice through loxP-mediated gene deletion. Mice with this double conditional mutation (double KO mice) showed reduced thymus and spleen size and cellularity. There was a significant decrease in the DN4, double positive, and single positive thymocyte subpopulations and mature CD4 and CD8 cells in the periphery. dKO thymocytes and peripheral T cells failed to compete with their WT counterparts in irradiated recipients, and the T cells showed compromised ability of homeostatic expansion. dKO naive T cells were inferior in differentiating into Th1 and Th17 effectors in vitro. The dKO mice showed diminished immune response against LCMV infection. Mechanistic studies revealed that IL-6 signaling in dKO T cells was compromised, in terms of abated induction of STAT3 phosphorylation upon IL-6 stimulation. This defect likely contributed to the observed in vitro and in vivo phenotype in dKO mice. This study revealed novel roles of Efnb1 and Efnb2 in T cell development and function.     

Comparative Analysis of the Fatty Acid Composition of Microalgae Obtained by Different Oil Extraction Methods and Direct Biomass Transesterification

One of the main challenges for the successful production and use of microalgae for biodiesel production is to obtain a satisfactory level of fatty acid methyl esters (FAME). The aims of this study are to identify the best method of lipid extraction and provide high FAME levels and to evaluate their fatty acid profiles. Six lipid extraction methodologies in three microalgae species were tested in comparison with the direct transesterification (DT) of microalgal biomass method. The choice of extraction method affected both the oily extract yield and the FAME composition of the microalgae and consequently may affect the properties of biodiesel. The efficiency of different lipid extraction methods is affected by the solvent polarity, which extracts different target compounds from lipid matrix. Dichloromethane/methanol extraction and Folch extraction produced the largest oil extract yields, but extraction with hexane/ethanol resulted in the best ester profile and levels. Performing DT reduces the volume of extractor solvent, the time and cost of FA composition analysis, as well as, presents less steps for fatty acid quantification. DT provided biomass FAME levels of 50.2, 636.4, and 258.2 mg.g^?1 in Nannochlorophisis oculata, Chaetoceros muelleri, and Chlorella sp., respectively. On the basis of an analysis of the fatty acids profiles of different species, C. muelleri is a promising microalga for biodiesel production. Depending on the extraction method, Chlorella sp. and N. oculata can be considered as an alternative in obtaining arachidonic (Aa) and eicosapentaenoic (EPA) acids.