A multicentre trial of voltaren in the treatment of rheumatoid arthritis

Voltaren, a compound with analgesic, anti-inflammatory and antipyretic properties, has been compared at two dose levels-25 mg t.d.s. and 50 mg t.d.s. with indomethacin 25 mg t.d.s. and acetylsalicylic acid 1 500 mg t.d.s. Ninety-one patients with definite or classical rheumatoid arthritis took part in this study. The trial was a doubleblind cross-over study, with each  medication being given for one week. Patients were washed out for one week prior to the first active treatment. Each patient received only two of the four possible treatments. Voltaren in a dose of 25 mg t.d.s. was found to improve the symptoms of rheumatoid arthritis to a greater degree than indomethacin or acetylsalicylic acid. Voltaren 50 mg t.d.s. evoked a greater response than acetylsalicylic acid and was at least as efficacious as indomethacin. Voltaren was better tolerated than either indomethacin or acetylsalicylic acid. The incidence of gastro-intestinal side-effects was similar with Voltaren and indomethacin, and half that produced by acetylsalicylic acid. Some evidence of possible drug interaction was found.S. Afr. Med. J., 48, 2013 (1974)

Maternal cadmium, iron and zinc levels, DNA methylation and birth weight

Background Cadmium (Cd) is a ubiquitous and environmentally persistent toxic metal that has been implicated in neurotoxicity, carcinogenesis and obesity and essential metals including zinc (Zn) and iron (Fe) may alter these outcomes. However mechanisms underlying these relationships remain limited. Methods We examined whether maternal Cd levels during early pregnancy were associated with offspring DNA methylation at regulatory sequences of genomically imprinted genes and weight at birth, and whether Fe and Zn altered these associations. Cd, Fe and Zn were measured in maternal blood of 319 women ≤12 weeks gestation. Offspring umbilical cord blood leukocyte DNA methylation at regulatory differentially methylated regions (DMRs) of 8 imprinted genes was measured using bisulfite pyrosequencing. Regression models were used to examine the relationships among Cd, Fe, Zn, and DMR methylation and birth weight. Results Elevated maternal blood Cd levels were associated with lower birth weight (p = 0.03). Higher maternal blood Cd levels were also associated with lower offspring methylation at the PEG3 DMR in females (β = 0.55, se = 0.17, p = 0.05), and at the MEG3 DMR in males (β = 0.72, se = 0.3, p = 0.08), however the latter association was not statistically significant. Associations between Cd and PEG3 and PLAGL1 DNA methylation were stronger in infants born to women with low concentrations of Fe (p < 0.05). Conclusions Our data suggest the association between pre-natal Cd and offspring DNA methylation at regulatory sequences of imprinted genes may be sex- and gene-specific. Essential metals such as Zn may mitigate DNA methylation response to Cd exposure. Larger studies are required

High frequency of Plasmodium falciparum chloroquine resistance marker (pfcrt T76 mutation) in Yemen: An urgent need to re-examine malaria drug policy

<p>Abstract</p> <p>Background</p> <p>Malaria remains a significant health problem in Yemen with <it>Plasmodium falciparum </it>being the predominant species which is responsible for 90% of the malaria cases. Despite serious concerns regarding increasing drug resistance, chloroquine is still used for the prevention and treatment of malaria in Yemen. This study was carried out to determine the prevalence of choloroquine resistance (CQR) of <it>P. falciparum </it>isolated from Yemen based on the <it>pfcrt </it>T76 mutation.</p> <p>Methods</p> <p>A cross-sectional study was carried out among 511 participants from four governorates in Yemen. Blood samples were screened using microscopic and species-specific nested PCR based on the 18S rRNA gene to detect and identify <it>Plasmodium </it>species. Blood samples positive for <it>P. falciparum </it>were used for detecting the <it>pfcrt </it>T76 mutation using nested-PCR.</p> <p>Results</p> <p>The prevalence of <it>pfcrt </it>T76 mutation was 81.5% (66 of 81 isolates). Coastal areas/foothills had higher prevalence of <it>pfcrt </it>T76 mutation compared to highland areas (90.5% <it>vs </it>71.8%) (p = 0.031). The <it>pfcrt </it>T76 mutation had a significant association with parasitaemia (p = 0.045). Univariate analysis shows a significant association of <it>pfcrt </it>T76 mutation with people aged > 10 years (OR = 9, 95% CI = 2.3 - 36.2, p = 0.001), low household income (OR = 5, 95% CI = 1.3 - 19.5, p = 0.027), no insecticide spray (OR = 3.7, 95% CI = 1.16 - 11.86, p = 0.025) and not sleeping under insecticide treated nets (ITNs) (OR = 4.8, 95% CI = 1.38 - 16.78, p = 0.01). Logistic regression model confirmed age > 10 years and low household income as predictors of <it>pfcrt </it>T76 mutation in Yemen <it>P. falciparum </it>isolates.</p> <p>Conclusions</p> <p>The high prevalence of <it>pfcrt </it>T76 mutation in Yemen could be a predictive marker for the prevalence of <it>P. falciparum </it>CQR. This finding shows the necessity for an in-vivo therapeutic efficacy test for CQ.<it> P. falciparum </it>CQR should be addressed in the national strategy to control malaria.</p

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Evaluation of two BDP preparations for the management of chronic asthma.

GesondheidswetenskappeInterne GeneeskundePlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]

The effect of the first glimpse at a scene on eye movements during search

Previewing scenes briefly makes finding target objects more efficient when viewing is through a gaze-contingent window (windowed viewing). In contrast, showing a preview of a randomly arranged search display does not benefit search efficiency when viewing during search is of the full display. Here, we tested whether a scene preview is beneficial when the scene is fully visible during search. Scene previews, when presented, were 250 ms in duration. During search, the scene was either fully visible or windowed. A preview always provided an advantage, in terms of decreasing the time to initially fixate and respond to targets and in terms of the total number of fixations. In windowed visibility, a preview reduced the distance of fixations from the target position until at least the fourth fixation. In full visibility, previewing reduced the distance of the second fixation but not of later fixations. The gist information derived from the initial glimpse of a scene allowed for placement of the first one or two fixations at information-rich locations, but when nonfoveal information was available, subsequent eye movements were only guided by online informatio

Segregation of lexical and sub-lexical reading processes in the left perisylvian cortex.

International audienceA fundamental issue in cognitive neuroscience is the existence of two major, sub-lexical and lexical, reading processes and their possible segregation in the left posterior perisylvian cortex. Using cortical electrostimulation mapping, we identified the cortical areas involved on reading either orthographically irregular words (lexical, "direct" process) or pronounceable pseudowords (sublexical, "indirect" process) in 14 right-handed neurosurgical patients while video-recording behavioral effects. Intraoperative neuronavigation system and Montreal Neurological Institute (MNI) stereotactic coordinates were used to identify the localization of stimulation sites. Fifty-one reading interference areas were found that affected either words (14 areas), or pseudo-words (11 areas), or both (26 areas). Forty-one (80%) corresponded to the impairment of the phonological level of reading processes. Reading processes involved discrete, highly localized perisylvian cortical areas with individual variability. MNI coordinates throughout the group exhibited a clear segregation according to the tested reading route; specific pseudo-word reading interferences were concentrated in a restricted inferior and anterior subpart of the left supramarginal gyrus (barycentre x = -68.1; y = -25.9; z = 30.2; Brodmann's area 40) while specific word reading areas were located almost exclusively alongside the left superior temporal gyrus. Although half of the reading interferences found were nonspecific, the finding of specific lexical or sublexical interferences is new evidence that lexical and sublexical processes of reading could be partially supported by distinct cortical sub-regions despite their anatomical proximity. These data are in line with many brain activation studies that showed that left superior temporal and inferior parietal regions had a crucial role respectively in word and pseudoword reading and were core regions for dyslexia