Response to novel objects and foraging tasks by common marmoset (Callithrix Jacchus) female Pairs

Many studies have shown that environmental enrichment can significantly improve the psychological well-being of captive primates, increasing the occurrence of explorative behavior and thus reducing boredom. The response of primates to enrichment devices may be affected by many factors such as species, sex, age, personality and social context. Environmental enrichment is particularly important for social primates living in unnatural social groupings (i.e. same-sex pairs or singly housed animals), who have very few, or no, benefits from the presence of social companions in addition to all the problems related to captivity (e.g. increased inactivity). This study analyses the effects of enrichment devices (i.e. novel objects and foraging tasks) on the behavior of common marmoset (Callithrix jacchus) female pairs, a species that usually lives in family groups. It aims to determine which aspects of an enrichment device are more likely to elicit explorative behaviors, and how aggressive and stress-related behaviors are affected by its presence. Overall, the marmosets explored foraging tasks significantly longer than novel objects. The type of object, which varied in size, shape and aural responsiveness (i.e. they made a noise when the monkey touched them), did not affect the response of the monkeys, but they explored objects that were placed higher in the enclosure more than those placed lower down.Younger monkeys were more attracted to the enrichment devices than the older ones. Finally, stress-related behavior (i.e. scratching) significantly decreased when the monkeys were presented with the objects; aggressive behavior as unaffected. This study supports the importance of environmental enrichment for captive primates and shows that in marmosets its effectiveness strongly depends upon the height of the device in the enclosure and the presence of hidden food. The findings can be explained ifone considers the foraging behavior of wild common marmosets. Broader applications for the research findings are suggested in relation to enrichment

Influence of arthritis and non-arthritis related factors on areal bone mineral density (BMDa) in women with longstanding inflammatory polyarthritis: a primary care based inception cohort

<p>Abstract</p> <p>Background</p> <p>The aim of this analysis was to determine the relative influence of disease and non-disease factors on areal bone mineral density (BMD_a) in a primary care based cohort of women with inflammatory polyarthritis.</p> <p>Methods</p> <p>Women aged 16 years and over with recent onset inflammatory polyarthritis were recruited to the Norfolk Arthritis Register (NOAR) between 1990 and 1993. Subjects were examined at both baseline and follow up for the presence of tender, swollen and deformed joints. At the 10^thanniversary visit, a sub-sample of women were invited to complete a bone health questionnaire and attend for BMD_a(Hologic, QDR 4000). Linear regression was used to examine the association between BMD_awith both (i) arthritis-related factors assessed at baseline and the 10^thanniversary visit and (ii) standard risk factors for osteoporosis. Adjustments were made for age.</p> <p>Results</p> <p>108 women, mean age 58.0 years were studied. Older age, decreasing weight and BMI at follow up were all associated with lower BMD_aat both the spine and femoral neck. None of the lifestyle factors were linked. Indices of joint damage including 10^thanniversary deformed joint count and erosive joint count were the arthritis-related variables linked with a reduction in BMD_aat the femoral neck. By contrast, disease activity as determined by the number of tender and or swollen joints assessed both at baseline and follow up was not linked with BMD_aat either site.</p> <p>Conclusion</p> <p>Cumulative disease damage was the strongest predictor of reduced femoral bone density. Other disease and lifestyle factors have only a modest influence.</p

The utility of clinical decision tools for diagnosing osteoporosis in postmenopausal women with rheumatoid arthritis

BACKGROUND: Patients with rheumatoid arthritis have a higher risk of low bone mineral density than normal age matched populations. There is limited evidence to support cost effectiveness of population screening in rheumatoid arthritis and case finding strategies have been proposed as a means to increase cost effectiveness of diagnostic screening for osteoporosis. This study aimed to assess the performance attributes of generic and rheumatoid arthritis specific clinical decision tools for diagnosing osteoporosis in a postmenopausal population with rheumatoid arthritis who attend ambulatory specialist rheumatology clinics. METHODS: A cross-sectional study of 127 ambulatory post-menopausal women with rheumatoid arthritis was performed. Patients currently receiving or who had previously received bone active therapy were excluded. Eligible women underwent clinical assessment and dual-energy-xray absorptiometry (DXA) bone mineral density assessment. Clinical decision tools, including those specific for rheumatoid arthritis, were compared to seven generic post-menopausal tools to predict osteoporosis (defined as T score < -2.5). Sensitivity, specificity, positive predictive and negative predictive values and area under the curve were assessed. The diagnostic attributes of the clinical decision tools were compared by examination of the area under the receiver-operator-curve. RESULTS: One hundred and twenty seven women participated. The median age was 62 (IQR 56-71) years. Median disease duration was 108 (60-168) months. Seventy two (57%) women had no record of a previous DXA examination. Eighty (63%) women had T scores at femoral neck or lumbar spine less than -1. The area under the ROC curve for clinical decision tool prediction of T score <-2.5 varied between 0.63 and 0.76. The rheumatoid arthritis specific decision tools did not perform better than generic tools, however, the National Osteoporosis Foundation score could potentially reduce the number of unnecessary DXA tests by approximately 45% in this population. CONCLUSION: There was limited utility of clinical decision tools for predicting osteoporosis in this patient population. Fracture prediction tools that include risk factors independent of BMD are needed

Thoracic and Lumbar Vertebral Bone Mineral Density Changes in a Natural Occurring Dog Model of Diffuse Idiopathic Skeletal Hyperostosis

Ankylosing spinal disorders can be associated with alterations in vertebral bone mineral density (BMD). There is however controversy about vertebral BMD in patients wuse idiopathic skeletal hyperostosis (DISH). DISH in Boxer dogs has been considered a natural occurring disease model for DISH in people. The purpose of this study was to compare vertebral BMD between Boxers with and without DISH. Fifty-nine Boxers with (n=30) or without (n=29) DISH that underwent computed tomography were included. Vertebral BMD was calculated for each thoracic and lumbar vertebra by using an earlier reported and validated protocol. For each vertebral body, a region of interest was drawn on the axial computed tomographic images at three separate locations: immediately inferior to the superior end plate, in the middle of the vertebral body, and superior to the inferior end plate. Values from the three axial slices were averaged to give a mean Hounsfield Unit value for each vertebral body. Univariate statistical analysis was performed to identify factors to be included in a multivariate model. The multivariate model including all dogs demonstrated that vertebral DISH status (Coefficient 24.63; 95% CI 16.07 to 33.19; p <0.001), lumbar vertebrae (Coefficient -17.25; 95% CI -23.42 to -11.09; p < 0.01), and to a lesser extent higher age (Coefficient -0.56; 95% CI -1.07 to -0.05; p = 0.03) were significant predictors for vertebral BMD. When the multivariate model was repeated using only dogs with DISH, vertebral DISH status (Coefficient 20.67; 95% CI, 10.98 to 30.37; p < 0.001) and lumbar anatomical region (Coefficient -38.24; 95% CI, -47.75 to -28.73; p < 0.001) were again predictors for vertebral BMD but age was not. The results of this study indicate that DISH can be associated with decreased vertebral BMD. Further studies are necessary to evaluate the clinical importance and pathophysiology of this finding

Contribution of a Common Variant in the Promoter of the 1-α-Hydroxylase Gene (CYP27B1) to Fracture Risk in the Elderly

CYP27B1 encodes mitochondrial 1α-hydroxylase, which converts 25-hydroxyvitamin D to its active 1,25-dihydroxylated metabolite. We tested the hypothesis that common variants in the CYP27B1 promoter are associated with fracture risk. The study was designed as a population-based genetic association study, which involved 153 men and 596 women aged 65–101 years, who had been followed for 2.2 years (range 0.1–5.5) between 1999 and 2006. During the follow-up period, the incidence of fragility fractures was ascertained. Bone ultrasound attenuation (BUA) was measured in all individuals, as were serum 25-hydroxyvitamin D and PTH concentrations; 86% subjects had vitamin D insufficiency. Genotypes were determined for the –1260C>A (rs10877012) and +2838T>C (rs4646536) CYP27B1 polymorphisms. A reporter gene assay was used to assess functional expression of the –1260C>A CYP27B1 variants. The association between genotypes and fracture risk was analyzed by Cox’s proportional hazards model. We found that genotypic distribution of CYP27B1 –1260 and CYP27B1 +2838 polymorphisms was consistent with the Hardy-Weinberg equilibrium law. The two polymorphisms were in high linkage disequilibrium, with D′ = 0.96 and r2 = 0.94. Each C allele of the CYP27B1 –1260 polymorphism was associated with increased risk of fracture (hazard ratio = 1.34, 95% CI 1.03–1.73), after adjustment for age, sex, number of falls, and BUA. In transient transfection studies, a reporter gene downstream of the –1260(A)-containing promoter was more highly expressed than that containing the C allele. These data suggest that a common but functional variation within the CYP27B1 promoter gene is associated with fracture risk in the elderly

Characteristics of patients initiating raloxifene compared to those initiating bisphosphonates

<p>Abstract</p> <p>Background</p> <p>Both raloxifene and bisphosphonates are indicated for the prevention and treatment of postmenopausal osteoporosis, however these medications have different efficacy and safety profiles. It is plausible that physicians would prescribe these agents to optimize the benefit/risk profile for individual patients. The objective of this study was to compare demographic and clinical characteristics of patients initiating raloxifene with those of patients initiating bisphosphonates for the prevention and treatment of osteoporosis.</p> <p>Methods</p> <p>This study was conducted using a retrospective cohort design. Female beneficiaries (45 years and older) with at least one claim for raloxifene or a bisphosphonate in 2003 through 2005 and continuous enrollment in the previous 12 months and subsequent 6 months were identified using a collection of large national commercial, Medicare supplemental, and Medicaid administrative claims databases (MarketScan^®). Patients were divided into two cohorts, a combined commercial/Medicare cohort and a Medicaid cohort. Within each cohort, characteristics (demographic, clinical, and resource utilization) of patients initiating raloxifene were compared to those of patients initiating bisphosphonate therapy. Group comparisons were made using chi-square tests for proportions of categorical measures and Wilcoxon rank-sum tests for continuous variables. Logistic regression was used to simultaneously examine factors independently associated with initiation of raloxifene versus a bisphosphonate.</p> <p>Results</p> <p>Within both the commercial/Medicare and Medicaid cohorts, raloxifene patients were younger, had fewer comorbid conditions, and fewer pre-existing fractures than bisphosphonate patients. Raloxifene patients in both cohorts were less likely to have had a bone mineral density (BMD) screening in the previous year than were bisphosphonate patients, and were also more likely to have used estrogen or estrogen/progestin therapy in the previous 12 months. These differences remained statistically significant in the multivariate model.</p> <p>Conclusion</p> <p>In this sample of patients enrolled in commercial, Medicare, and Medicaid plans, patients who initiated raloxifene treatment differed from those initiating bisphosphonates. Raloxifene patients were younger, had better overall health status and appeared to be less likely to have risk factors for new osteoporotic fractures than bisphosphonate patients. Differences in the clinical profiles of these agents may impact prescribing decisions. Investigators using observational data to make comparisons of treatment outcomes associated with these medications should take these important differences in patient characteristics into consideration.</p

The association between subgroups of MRI findings identified with latent class analysis and low back pain in 40-year old Danes

Background: Research into the clinical importance of spinal MRI findings in patients with low back pain (LBP) has primarily focused on single imaging findings, such as Modic changes or disc degeneration, and found only weak associations with the presence of pain. However, numerous MRI findings almost always co-exist in the lumbar spine and are often present at more than one lumbar level. It is possible that multiple MRI findings are more strongly associated with LBP than single MRI findings. Latent Class Analysis is a statistical method that has recently been tested and found useful for identifying latent classes (subgroups) of MRI findings within multivariable datasets. The purpose of this study was to investigate the association between subgroups of MRI findings and the presence of LBP in people from the general population. Methods: To identify subgroups of lumbar MRI findings with potential clinical relevance, Latent Class Analysis was initially performed on a clinical dataset of 631 patients seeking care for LBP. Subsequently, 412 participants in a general population cohort (the ‘Backs on Funen’ project) were statistically allocated to those existing subgroups by Latent Class Analysis, matching their MRI findings at a segmental level. The subgroups containing MRI findings from the general population were then organised into hypothetical pathways of degeneration and the association between subgroups in the pathways and the presence of LBP was tested using exact logistic regression. Results: Six subgroups were identified in the clinical dataset and the data from the general population cohort fitted the subgroups well, with a median posterior probability of 93%–100%. These six subgroups described two pathways of increasing degeneration on upper (L1-L3) and lower (L4-L5) lumbar levels. An association with LBP was found for the subgroups describing severe and multiple degenerative MRI findings at the lower lumbar levels but none of the other subgroups were associated with LBP

Bone mineral density by digital X-ray radiogrammetry is strongly decreased and associated with joint destruction in long-standing Rheumatoid Arthritis: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The aims were to explore bone mineral density (BMD) by digital X-ray radiogrammetry (DXR) in postmenopausal women with long-lasting rheumatoid arthritis (RA) in relation to dual x-ray absorptiometry (DXA)-BMD, joint destruction by conventional radiographs and disease related variables in a cross-sectional study.</p> <p>Methods</p> <p>Seventy-five postmenopausal women with RA were examined by DXA measuring DXA-BMD of the forearm, total hip and lumbar spine, by scoring joint destruction on plain radiographs by the method of Larsen and by DXR-BMD in metacarpals two to four. The DXR-BMD results of the RA women were compared with an age and sex-matched reference database. A function of DXR-BMD in relation to age and disease duration was created. Associations were investigated by bivariate and multiple linear regression analyses.</p> <p>Results</p> <p>DXR-BMD was strongly decreased in RA patients compared to the reference database (p < 0.001). Calculations showed that DXR-BMD was not markedly influenced the first years after diagnosis of RA, but between approximately 5-10 years of disease there was a steep decline in DXR-BMD which subsequently levelled off. In multiple regression analyses disease duration, CRP and DXR-BMD were independent variables associated with Larsen score (R²= 0.64). Larsen score and BMD forearm were independent determinants of DXR-BMD (R²= 0.79).</p> <p>Conclusions</p> <p>DXR-BMD was strongly reduced and associated with both Larsen score and DXA-BMD forearm in these postmenopausal women with RA implying that DXR-BMD is a technique that reflects both the erosive process and bone loss adjacent to affected joints.</p

A quantitative PCR (TaqMan) assay for pathogenic Leptospira spp

BACKGROUND: Leptospirosis is an emerging infectious disease. The differential diagnosis of leptospirosis is difficult due to the varied and often "flu like" symptoms which may result in a missed or delayed diagnosis. There are over 230 known serovars in the genus Leptospira. Confirmatory serological diagnosis of leptospirosis is usually made using the microscopic agglutination test (MAT) which relies on the use of live cultures as the source of antigen, often performed using a panel of antigens representative of local serovars. Other techniques, such as the enzyme linked immunosorbent assay (ELISA) and slide agglutination test (SAT), can detect different classes of antibody but may be subject to false positive reactions and require confirmation of these results by the MAT. METHODS: The polymerase chain reaction (PCR) has been used to detect a large number of microorganisms, including those of clinical significance. The sensitivity of PCR often precludes the need for isolation and culture, thus making it ideal for the rapid detection of organisms involved in acute infections. We employed real-time (quantitative) PCR using TaqMan chemistry to detect leptospires in clinical and environmental samples. RESULTS AND CONCLUSIONS: The PCR assay can be applied to either blood or urine samples and does not rely on the isolation and culture of the organism. Capability exists for automation and high throughput testing in a clinical laboratory. It is specific for Leptospira and may discriminate pathogenic and non-pathogenic species. The limit of detection is as low as two cells

LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea, spherophakia, and secondary glaucoma

The latent TGFβ-binding proteins (LTBPs) and fibrillins are a superfamily of large, multidomain proteins with structural and TGFβ-signalling roles in the extracellular matrix. Their importance is underscored by fibrillin-1 mutations responsible for Marfan syndrome, but their respective roles are still incompletely understood. We report here on two families where children from healthy, consanguineous parents, presented with megalocornea and impaired vision associated with small, round, dislocated lenses (microspherophakia and ectopia lentis) and myopia, as well as a high-arched palate, and, in older children, tall stature with an abnormally large arm span over body height ratio, that is, associated features of Marfan syndrome. Glaucoma was not present at birth, but was diagnosed in older children. Whole genome homozygosity mapping followed by candidate gene analysis identified homozygous truncating mutations of LTBP2 gene in patients from both families. Fibroblast mRNA analysis was consistent with nonsense-mediated mRNA decay, with no evidence of mutated exon skipping. We conclude that biallelic null LTBP2 mutations cause the ocular phenotype in both families and could lead to Marfan-like features in older children. We suggest that intraocular pressures should be followed-up in young children with an ocular phenotype consisting of megalocornea, spherophakia and/or lens dislocation, and recommend LTBP2 gene analysis in these patients