The CUPID (Cultural and Psychosocial Influences on Disability) study: methods of data collection and characteristics of study sample

Background

The CUPID (Cultural and Psychosocial Influences on Disability) study was established to explore the hypothesis that common musculoskeletal disorders (MSDs) and associated disability are importantly influenced by culturally determined health beliefs and expectations. This paper describes the methods of data collection and various characteristics of the study sample.

Methods/Principal Findings

A standardised questionnaire covering musculoskeletal symptoms, disability and potential risk factors, was used to collect information from 47 samples of nurses, office workers, and other (mostly manual) workers in 18 countries from six continents. In addition, local investigators provided data on economic aspects of employment for each occupational group. Participation exceeded 80% in 33 of the 47 occupational groups, and after pre-specified exclusions, analysis was based on 12,426 subjects (92 to 1018 per occupational group). As expected, there was high usage of computer keyboards by office workers, while nurses had the highest prevalence of heavy manual lifting in all but one country. There was substantial heterogeneity between occupational groups in economic and psychosocial aspects of work; three- to five-fold variation in awareness of someone outside work with musculoskeletal pain; and more than ten-fold variation in the prevalence of adverse health beliefs about back and arm pain, and in awareness of terms such as “repetitive strain injury” (RSI).

Conclusions/Significance

The large differences in psychosocial risk factors (including knowledge and beliefs about MSDs) between occupational groups should allow the study hypothesis to be addressed effectively.     

GenoSNP: a variational Bayes within-sample SNP genotyping algorithm that does not require a reference population

Current genotyping algorithms typically call genotypes by clustering allele-specific intensity data on a single nucleotide polymorphism (SNP) by SNP basis. This approach assumes the availability of a large number of control samples that have been sampled on the same array and platform. We have developed a SNP genotyping algorithm for the Illumina Infinium SNP genotyping assay that is entirely within-sample and does not require the need for a population of control samples nor parameters derived from such a population. Our algorithm exhibits high concordance with current methods and >99% call accuracy on HapMap samples. The ability to call genotypes using only within-sample information makes the method computationally light and practical for studies involving small sample sizes and provides a valuable independent quality control metric for other population-based approaches. AVAILABILITY: http://www.stats.ox.ac.uk/~giannoul/GenoSNP/.     

Benthic colonization and succession on temperate sublittoral rocky cliffs

Patterns of benthic colonization and succession were investigated on a temperate rocky cliff (Aegean Sea, Eastern Mediterranean). Cement and ceramic panels deployed on the rocky substratum at 25-30 m depth were sampled every 3 months over a 2-year period yielding 28 floral and 156 animal species. Diversity, cover and abundance had low values at short immersion periods and increased at the long ones. The vagile fauna responded to the increasing habitat complexity offered by the development of algal turfs and sessile species, and the community structure remained highly dynamic. Unlike the duration of immersion, the type of substratum didn't affect species colonization except for decapods that showed a preference for cement panels. Three to four stages of succession were recorded over immersion periods, according to vagile and sessile biota, respectively, during which species richness and abundance increased. The structure of the developed communities on both artificial materials differed from the natural algal-dominated benthic community of the same area, suggesting that the recovery of rocky shore communities on temperate cliffs is time consuming.     

Chmp4c is required for stable kinetochore-microtubule attachments

Formation of stable kinetochore-microtubule attachments is essential for accurate chromosome segregation in human cells and depends on the NDC80 complex. We recently showed that Chmp4c, an endosomal sorting complex required for transport protein involved in membrane remodelling, localises to prometaphase kinetochores and promotes cold-stable kinetochore microtubules, faithful chromosome alignment and segregation. In the present study, we show that Chmp4c associates with the NDC80 components Hec1 and Nuf2 and is required for optimal NDC80 stability and Hec1-Nuf2 localisation to kinetochores in prometaphase. However, Chmp4c-depletion does not cause a gross disassembly of outer or inner kinetochore complexes. Conversely, Nuf2 is required for Chmp4c kinetochore targeting. Constitutive Chmp4c kinetochore tethering partially rescues cold-stable microtubule polymers in cells depleted of the endogenous Nuf2, showing that Chmp4c also contributes to kinetochore-microtubule stability independently of regulating Hec1 and Nuf2 localisation. Chmp4c interacts with tubulin in cell extracts, and binds and bundles microtubules in vitro through its highly basic N-terminal region (amino acids 1–77). Furthermore, the N-terminal region of Chmp4c is required for cold-stable kinetochore microtubules and efficient chromosome alignment. We propose that Chmp4c promotes stable kinetochore-microtubule attachments by regulating Hec1–Nuf2 localisation to kinetochores in prometaphase and by binding to spindle microtubules. These results identify Chmp4c as a novel protein that regulates kinetochore-microtubule interactions to promote accurate chromosome segregation in human cells.     

Seasonal variation in whole blood cytokine production after LPS stimulation in normal individuals

We examined seasonal differences in whole blood cytokine production after endotoxin (LPS) stimulation in 17 healthy individuals from an urban area having normal sleep/wakefulness pattern. We used 500 pg/ml of LPS for incubation period of 4 h to stimulate 100 microl of whole blood of the same subjects in June, September, February, and March. We found no differences in the circulating total WBCs and differentials including monocytes between different seasons. We found during September (autumn) a reduced pro-inflammatory cytokine production in terms of TNF-alpha and IL-6 production compared to the other seasons. We also found a reduced anti-inflammatory cytokine production in June (summer) and September (autumn) in terms of IL-10, TNF-RI and TNF-RII compared to February (winter) and March (spring). Our results suggest that in early summer there is a predominating pro-inflammatory cytokine response which is counterbalanced early in autumn. These results may have significant implications in the determination of reference values, in exploration of immune response and inflammatory disease prevalence between different seasons, in determining LPS tolerance (immunoparalysis) and planning clinical trials and immunomodulary therapies. However, the effect of dark/light exposure differences on the circadian periodicity in the responsiveness of immune cells during different seasons should be further investigated.     

Sex hormones in postmenopausal women receiving low-dose hormone therapy: the effect of BMI

The aim of our study was to evaluate the effect of BMI on the change in circulating sex hormone in postmenopausal women during 6 months of oral continuous combined low-dose hormone therapy (HT). Fifty postmenopausal women were allocated to receive daily one tablet containing combination of 17β-estradiol (1 mg)/norethindrone acetate (0.5 mg) for 6 months. Serum levels of follicle-stimulating hormone (FSH), estradiol, total testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), free estrogen index (FEI), Δ4-androstendione (Δ4A), and dehydroepiandrosterone sulfate were assessed at baseline and at the end of 6 months. Mean absolute values and percent changes from baseline were compared between lean and overweight women. Mean FSH decreased and mean 17β-estradiol increased significantly in both groups (FSH lean: 82.3 ± 26.7 decreased to 45.0 ± 17.0 mIU/ml, P = 0.0001; FSH overweight: 85.5 ± 22.1 decreased to 52.3 ± 23.8 mIU/ml, P = 0.003; P between groups = 0.661; E2 lean: 23.24 ± 12.55 increased to 53.62 ± 28.29 pg/ml, P = 0.006; E2 overweight: 24.17 ± 10.88 increased to 68.36 ± 53.99 pg/ml, P = 0.0001; P between groups = 0.619). Lean individuals had statistically significant higher increments of FAI and specifically FEI compared to overweight (FEI lean; 0.14 ± 0.09 increased to 0.29 ± 0.14, P = 0.009; overweight 0.23 ± 0.18 increased to 0.52 ± 0.40, P = 0.126; P between groups = 0.034). Although BMI does not affect total 17β-estradiol changes, free sex steroid concentrations increase more steeply in lean compared to overweight women receiving oral low-dose HT.     

Synthesis and biological evaluation of novel angular fused Pyrrolocoumarins

Angular pyrrolocoumarins were synthesized from the reaction of 4-hydroxyindole or 5-hydroxyindole with DMAD and PPh(3) and were tested for anti-inflammatory and antioxidant activity. These compounds significantly inhibited the carrageenin-induced paw edema (60.5%-73.4%) and have important scavenging activity. Although their interaction with the free stable radical DPPH is not high, compound 9 is the most potent (73.4%) in the in vivo experiment. Compound 7 seems to be a potent LOX inhibitor. An attempt was made to correlate the biological results with their structural characteristics and physicochemical parameters.     

Effect of training on the muscle strength and dynamic balance ability of adults with down syndrome

The purpose of this study was to evaluate the effect of training on the muscle strength and dynamic balance ability of adults with Down syndrome (DS). Twenty-five adults with DS were separated into 2 groups. Fifteen subjects (mean age, 24.5 years) constituted the experiment group, whereas 10 subjects (mean age, 24.7 years) were in the control group of the study. Parameters measured were peak torque, isokinetic muscle endurance, and dynamic balance ability. All subjects performed a leg strength test on a Cyber II isokinetic dynamometer. In addition, the subjects' dynamic balance ability was measured by means of a balance deck (Lafayette). The experimental group followed a 12-week training program. As the results indicated, the experimental group showed a statistically significant improvement in all measured values when compared with the control group. It is concluded that adults with DS can improve their physical and kinetic abilities with the application of a systematic and well-designed training program.