Use of methotrexate therapy is not associated with decreased prevalence of metabolic syndrome

With great interest, we read the article by Toms and colleagues [1] in the previous issue of Arthritis Research & Therapy, in which they assessed prevalences of metabolic syndrome (MetS) in rheumatoid arthritis (RA) patients. Moreover, they identified demographic and clinical factors that may be associated with MetS. Toms and colleagues found prevalences of up to 45% of MetS and demonstrated older age and health status (health assessment questionnaire) to be associated with MetS irrespectively of the definition used. Of most interest, an association between methotrexate (MTX) use and decreased presence of MetS was observed in patients more than 60 years of age. The investigators hypothesized that this may be attributed to a drug-specific effect (and not to an anti-inflammatory effect) either by changing levels of adenosine, which is known to interact with glucose and lipid metabolism, or by an indirect effect mediated through concomitant folic acid administration, thereby decreasing homocysteine levels.Recently, we also examined the prevalence of MetS in (a subgroup of) RA patients in the CARRÉ investigation, a prospective cohort study on prevalent and incident cardiovascular disease and its underlying cardiovascular risk factors [2]. The findings of Toms and colleagues stimulated us to perform additional analyses in our total study population (n = 353).The prevalences of MetS were 35% and 25% (Table ​(Table1)1) according to criteria of National Cholesterol Education Program (NCEP) 2004 and NCEP 2001, respectively. In multivariate backward regression analyses, we found significant associations between body mass index, pulse rate, creatinine levels, hypothyroidism and diabetes mellitus and the presence of MetS independently of the criteria used (Table ​(Table2).2). However, an independent association between single use of MTX or use of MTX in combination with other disease-modifying antirheumatic drugs, on the one hand, and a decreased prevalence of MetS, on the other hand, could not be demonstrated (even in the subgroup of patients over the age of 60).

Table 1

Characteristics of the study population

Genome-wide analysis of core promoter elements from conserved human and mouse orthologous pairs

Background  

The canonical core promoter elements consist of the TATA box, initiator (Inr), downstream core promoter element (DPE), TFIIB recognition element (BRE) and the newly-discovered motif 10 element (MTE). The motifs for these core promoter elements are highly degenerate, which tends to lead to a high false discovery rate when attempting to detect them in promoter sequences.     

Presence of Bacteroidales as a Predictor of Pathogens in Surface Waters of the Central California Coast

The value of Bacteroidales genetic markers and fecal indicator bacteria (FIB) to predict the occurrence of waterborne pathogens was evaluated in ambient waters along the central California coast. Bacteroidales host-specific quantitative PCR (qPCR) was used to quantify fecal bacteria in water and provide insights into contributing host fecal sources. Over 140 surface water samples from 10 major rivers and estuaries within the Monterey Bay region were tested over 14 months with four Bacteroidales-specific assays (universal, human, dog, and cow), three FIB (total coliforms, fecal coliforms, and enterococci), two protozoal pathogens (Cryptosporidium and Giardia spp.), and four bacterial pathogens (Campylobacter spp., Escherichia coli O157:H7, Salmonella spp., and Vibrio spp.). Indicator and pathogen distribution was widespread, and detection was not highly seasonal. Vibrio cholerae was detected most frequently, followed by Giardia, Cryptosporidium, Salmonella, and Campylobacter spp. Bayesian conditional probability analysis was used to characterize the Bacteroidales performance assays, and the ratios of concentrations determined using host-specific and universal assays were used to show that fecal contamination from human sources was more common than livestock or dog sources in coastal study sites. Correlations were seen between some, but not all, indicator-pathogen combinations. The ability to predict pathogen occurrence in relation to indicator threshold cutoff levels was evaluated using a weighted measure that showed the universal Bacteroidales genetic marker to have a comparable or higher mean predictive potential than standard FIB. This predictive ability, in addition to the Bacteroidales assays providing information on contributing host fecal sources, supports using Bacteroidales assays in water quality monitoring programs.Coastal waters worldwide have been influenced by human activities for centuries, as they are adjacent to densely populated areas, provide a means of transportation, and receive substantial recreational use. Consequently, impairments in nearshore water quality can result from enrichment of the coastal marine ecosystem with pollutants and nutrients that are transported down watersheds from land to sea. This poses health risks to humans and animals. Microbial pollution is caused by fecal contamination from a variety of sources, including humans, livestock, pets, and wildlife, and fecal pathogen pollution has been associated with numerous outbreaks of waterborne disease (14, 15, 27, 41, 49, 55).Fecal indicator bacteria (FIB) that normally reside in the gastrointestinal tracts of humans and animals are used throughout the world to assess the microbiological quality of drinking and recreational waters. In the United States, FIB are used to define bacterial water quality standards aimed at reducing health risks in recreational waters, as required by the Beaches Environmental Assessment and Coastal Health Act (5), which amended the Clean Water Act (11). Groups of standard FIB monitored in water include total coliforms (TC), fecal coliforms (FC), Escherichia coli bacteria, and enterococci. These bacterial groups have been considered indicators of health risks in epidemiologic and quantitative microbial risk assessment (QMRA) studies (38, 42, 59, 66).To date, many monitoring programs have focused only on FIB measurements and do not test for pathogens. However, substantial evidence has been collected that challenges the usefulness of FIB data alone. A few limitations of using standard FIB to represent pathogens in water include the fact that FIB have been shown to multiply in the environment, that they are not host specific, and that the absence of FIB is not necessarily evidence of pathogen absence (21, 50, 51, 56). Consequently, alternative indicators of fecal pollution that address the weaknesses of standard FIB are needed. Ideally, these indicators would decay at rates similar to those of pathogens, be present at high concentrations in fecal sources, and be present at low concentrations in unpolluted environments. Proposed alternative indicators include (i) anaerobic bacteria such as bifidobacteria (46), Clostridium perfringens (22), and Bacteroidales (20); (ii) viruses such as F-specific RNA (F-RNA)-specific coliphages (39), phages infecting Bacteroides fragilis (30), and host-specific viruses (25); and (iii) chemical compounds such as fecal sterols (29). An added benefit of using alternative indicators is that, in some cases, host sources of fecal contamination can be identified.Over a decade ago, PCR-based assays were developed to detect Bacteroides in an effort to monitor human fecal pollution in the environment (36, 37). This approach was adopted by others and further advanced to identify host-specific Bacteroidales 16S rRNA gene markers for different fecal sources. This has resulted in PCR and quantitative PCR (qPCR) assays for the detection of human, dog, pig, and cow Bacteroidales markers (6, 7, 16, 34, 57) as well as assays for the detection of general Bacteroidales markers (7, 34). The analysis of Bacteroidales markers has been incorporated in microbial source tracking (MST) studies, particularly in the United States, Japan, and Europe (24, 45, 52-54, 64).The objective of this study was to compare the abilities of Bacteroidales markers and FIB to predict the occurrence of waterborne pathogens in riverine and estuarine waters in California and to use several statistical approaches to better characterize the strengths and limitations of the assays. We hypothesized that Bacteroidales and FIB would correlate with bacterial and protozoal pathogen detection in surface waters. To test this hypothesis, four Bacteroidales-specific assays (universal, human, dog, and cow), three types of FIB (total coliforms, fecal coliforms, and enterococci), two protozoal pathogens (Cryptosporidium and Giardia spp.), and four bacterial pathogens (Campylobacter spp., E. coli O157, Salmonella spp., and Vibrio spp.) were monitored monthly for 14 months in 10 streams, rivers, and estuaries feeding into the Monterey Bay region of California.     

Chromosome spreading of associated transposable elements and ribosomal DNA in the fish Erythrinus erythrinus. Implications for genome change and karyoevolution in fish

Background  

The fish, Erythrinus erythrinus, shows an interpopulation diversity, with four karyomorphs differing by chromosomal number, chromosomal morphology and heteromorphic sex chromosomes. Karyomorph A has a diploid number of 2n = 54 and does not have differentiated sex chromosomes. Karyomorph D has 2n = 52 chromosomes in females and 2n = 51 in males, and it is most likely derived from karyomorph A by the differentiation of a multiple X₁X₂Y sex chromosome system. In this study, we analyzed karyomorphs A and D by means of cytogenetic approaches to evaluate their evolutionary relationship.     

Levels of anti-citrullinated protein antibodies and IgM rheumatoid factor are not associated with outcome in early arthritis patients: a cohort study

Introduction  

To investigate whether baseline levels of anti-citrullinated protein antibody (ACPA) or IgM rheumatoid factor (IgM-RF) and changes in the year thereafter are associated with disease activity, functional and radiographic outcome in early arthritis patients, and provide additional information over baseline autoantibody status.     

Phylogeography of Plathymenia reticulata (Leguminosae) reveals patterns of recent range expansion towards northeastern Brazil and southern Cerrados in Eastern Tropical South America

Little is known about past vegetation dynamics in Eastern Tropical South America (ETSA). Here we describe patterns of chloroplast (cp) DNA variation in Plathymenia reticulata, a widespread tree in the ETSA Atlantic Forest and Cerrado biomes, but not found in the xeromorphic Caatinga. Forty one populations, comprising 220 individuals, were analysed by sequencing the trnS‐trnG and trnL‐trnL‐trnF cpDNA regions. Combined, they resulted in 18 geographically structured haplotypes. The central region of the sampling area, comprising Minas Gerais and Goiás Brazilian states, is a centre of genetic diversity and probably the most longstanding area of the distribution range of the species. In contrast, populations from northeastern Brazil and the southern Cerrados showed very low diversity levels, almost exclusively with common haplotypes which are also found in the central region. Coupled with a long‐branched star‐like network, these patterns suggest a recent range expansion of P. reticulata to those regions from central region sources. The recent origin of the species (in the early Pleistocene) or the extinction of some populations due to drier and cooler climate during the last glacial maximum could have been responsible for that phylogeographic pattern. The populations from northeastern Brazil originated from two colonization routes, one eastern (Atlantic) and one western (inland). Due to its high diversity and complex landscape, the central region, especially central‐north Minas Gerais (between 15°–18° S and 42°–46° W), should be given the highest priority for conservation.     

Activation of Cell Cycle Regulatory Proteins in the Apoptosis of Terminally Differentiated Oligodendrocytes

There is increasing evidence that proteins normally involved in the cell cycle play a role in the regulation of neuronal apoptotic death following various insults. However, it is not clear if the same mechanisms regulate cell death of oligodendrocytes as well. In this study, we investigated the mechanism of ceramide-induced apoptosis in primary rat oligodendrocytes. We show that ceramide treatment initiates a cascade of biochemical events involving cell cycle regulatory proteins. Although at the time of induction of cell death the oligodendrocytes are postmitotic, activation of c-myc and translocation of Cdc25A into the nucleus can be demonstrated. Of particular interest are the findings of the up-regulation of PCNA and down-regulation of p21WAF1/CIP1 protein, an inhibitor of cell-cycle progression. The current results show that activation of regulatory cell-cycle proteins at the oligodendrocytes G1-S checkpoint may constitute a crucial step of the death pathway of oligodendrocytes.     

The murine interleukin 1 beta gene: structure and evolution.

We have isolated from a genomic library a murine recombinant clone containing the gene coding for interleukin-1 beta m-RNA. A 7000 b.p. DNA fragment has been sequenced. Sequences homologous with human IL-1 beta cDNA have been found distributed within 7 exons. The translation of these sequences allows the prediction of a protein 269 aminoacids long. Hybridization of P388D1 RNA from cells stimulated with phorbol myristic acetate with a genomic DNA probe shows the existence of a 1.6 Kb murine IL-1 beta mRNA which is absent in the unstimulated cells. The comparative analysis between the murine IL-1 beta and the human IL-1 alpha genes shows extreme conservation of the aminoacids at the exon junctions. This observation together with the similarity in number and size of the exons suggests that these genes have diverged from a common ancestor.