Aberrant axial mineralization precedes spinal ankylosis: a molecular imaging study in ank/ank mice

Introduction

The diagnosis of ankylosing spondylitis is made from a combination of clinical features and the presence of radiographic evidence that may be detected only after many years of inflammatory back pain. It is not uncommon to have a diagnosis confirmed 5 to 10 years after the initial onset of symptoms. Development of a more-sensitive molecular imaging technology to detect structural changes in the joints would lead to earlier diagnosis and quantitative tracking of ankylosis progression. Progressive ankylosis (ank/ank) mice have a loss of function in the Ank gene, which codes for a regulator of PPi transport. In this study, we used these ank/ank mutant mice to assess a noninvasive, quantitative measure of joint ankylosis with near-infrared (NIR) molecular imaging in vivo.

Methods

Three age groups (8, 12, and 18 weeks) of ank/ank (15 mice) and wild-type littermates (12 +/+ mice) were assessed histologically and radiographically. Before imaging, OsteoSense 750 (bisphosphonate pamidronate) was injected i.v. Whole-body images were analyzed by using the multispectral Maestro imaging system.

Results

OsteoSense 750 signals in the paw joints were higher in ank/ank mice in all three age groups compared with controls. In the spine, significantly higher OsteoSense 750 signals were detected early, in 8-week-old ank/ank mice compared with controls, although minimal radiographic differences were noted at this time point. The molecular imaging changes in the ank/ank spine (8 weeks) were supported by histologic changes, including calcium apatite crystals at the edge of the vertebral bodies and new syndesmophyte formation.

Conclusions

Changes in joint pathology of ank/ank mice, as evaluated by histologic and radiographic means, are qualitative, but only semiquantitative. In contrast, molecular imaging provides a quantitative assessment. Ankylosis in ank/ank mice developed simultaneously in distal and axial joints, contrary to the previous notion that it is a centripetal process. NIR imaging might be feasible for early disease diagnosis and for monitoring disease progression in ankylosing spondylitis.     

Le syndrome de Klinefelter à 20 ans: A propos de 426 observations

Based on a personal series of 426 consecutive observations, the authors look into the different clinical, psychological and biological aspects of Klinefelter' syndrome in subjects aged around twenty. They emphasize the misleading forms and the need to get the karyotype in all patients presenting with any genitalia or pubertal development abnormalities. Testosterone treatment must be given as early as possible around the age of 11–12 years. This therapy is always beneficial in all aspects including the improvement of the psychosocial adjustment.     

Red-Shouldered Hawk Occupancy Surveys in Central Minnesota,USA

ABSTRACT Forest-dwelling raptors are often difficult to detect because many species occur at low density or are secretive. Broadcasting conspecific vocalizations can increase the probability of detecting forest-dwelling raptors and has been shown to be an effective method for locating raptors and assessing their relative abundance. Recent advances in statistical techniques based on presence—absence data use probabilistic arguments to derive probability of detection when it is < 1 and to provide a model and likelihood-based method for estimating proportion of sites occupied. We used these maximum-likelihood models with data from red-shouldered hawk (Buteo lineatus) call-broadcast surveys conducted in central Minnesota, USA, in 1994–1995 and 2004–2005. Our objectives were to obtain estimates of occupancy and detection probability 1) over multiple sampling seasons (yr), 2) incorporating within-season time-specific detection probabilities, 3) with call type and breeding stage included as covariates in models of probability of detection, and 4) with different sampling strategies. We visited individual survey locations 2–9 times per year, and estimates of both probability of detection (range = 0.28-0.54) and site occupancy (range = 0.81-0.97) varied among years. Detection probability was affected by inclusion of a within-season time-specific covariate, call type, and breeding stage. In 2004 and 2005 we used survey results to assess the effect that number of sample locations, double sampling, and discontinued sampling had on parameter estimates. We found that estimates of probability of detection and proportion of sites occupied were similar across different sampling strategies, and we suggest ways to reduce sampling effort in a monitoring program.