18F-Fluorodeoxyglucose Positron Emission Tomography in Elderly Patients with an Elevated Erythrocyte Sedimentation Rate of Unknown Origin

Patients with an elevated erythrocyte sedimentation rate (ESR) and non-specific symptoms often pose a diagnostic dilemma. PET/CT visualises infection, inflammation and malignancy, all of which may cause elevated ESR. The objective of this study was to determine the contribution of 18F-fluorodeoxglucose positron emission tomography (PET/CT) in the diagnostic work-up of referred patients with an elevated ESR, in whom initial routine evaluation did not reveal a diagnosis. We conducted a combined retrospective (A) and prospective (B) study in elderly (>50 years) patients with a significantly elevated ESR of≥50 mm/h and non-specific complaints. In study A, 30 patients were included. Malignancy (8 patients), auto-inflammatory disease (8 patients, including 5 with large-vessel vasculitis) and infection (3 patients) were suggested by PET/CT. Two scans showed non-specific abnormalities and 9 scans were normal. Of the 21 abnormal PET/CT results, 12 diagnoses were independently confirmed and two alternative diagnosis were made. Two diagnoses were established in patients with a normal scan. In study B, 58 patients in whom a prior protocolised work-up was non-diagnostic, were included. Of these, 25 PET/CT-scans showed suspected auto-inflammatory disease, particularly large-vessel vasculitis (14 cases). Infection and malignancy was suspected in 5 and 3 cases, respectively. Seven scans demonstrated non-specific abnormalities, 20 were normal. Of the 40 abnormal PET/CT results, 22 diagnoses were confirmed, 3 alternative diagnoses were established. Only one diagnosis was established in the 20 patients with a normal scan. In both studies, the final diagnosis was based on histology, clinical follow-up, response to therapy or additional imaging. In conclusion, PET/CT may be of potential value in the diagnostic work-up of patients with elevated ESR if routine evaluation reveals no diagnosis. In particular, large-vessel vasculitis appears to be a common finding. A normal PET/CT scan in these patients suggests that it is safe to follow a wait-and-see policy.     

Diagnosing Fatty Liver Disease: A Comparative Evaluation of Metabolic Markers,Phenotypes, Genotypes and Established Biomarkers

Background

To date, liver biopsy is the only means of reliable diagnosis for fatty liver disease (FLD). Owing to the inevitable biopsy-associated health risks, however, the development of valid noninvasive diagnostic tools for FLD is well warranted.

Aim

We evaluated a particular metabolic profile with regard to its ability to diagnose FLD and compared its performance to that of established phenotypes, conventional biomarkers and disease-associated genotypes.

Methods

The study population comprised 115 patients with ultrasound-diagnosed FLD and 115 sex- and age-matched controls for whom the serum concentration was measured of 138 different metabolites, including acylcarnitines, amino acids, biogenic amines, hexose, phosphatidylcholines (PCs), lyso-PCs and sphingomyelins. Established phenotypes, biomarkers, disease-associated genotypes and metabolite data were included in diagnostic models for FLD using logistic regression and partial least-squares discriminant analysis. The discriminative power of the ensuing models was compared with respect to area under curve (AUC), integrated discrimination improvement (IDI) and by way of cross-validation (CV).

Results

Use of metabolic markers for predicting FLD showed the best performance among all considered types of markers, yielding an AUC of 0.8993. Additional information on phenotypes, conventional biomarkers or genotypes did not significantly improve this performance. Phospholipids and branched-chain amino acids were most informative for predicting FLD.

Conclusion

We show that the inclusion of metabolite data may substantially increase the power to diagnose FLD over that of models based solely upon phenotypes and conventional biomarkers.     

T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?

Introduction

A hallmark of systemic autoimmune diseases like systemic lupus erythematosus (SLE) is the increased expression of interferon (IFN) type I inducible genes, so-called IFN type I signature. Recently, T-helper 17 subset (Th17 cells), which produces IL-17A, IL-17F, IL-21, and IL-22, has been implicated in SLE. As CCR6 enriches for Th17 cells, we used this approach to investigate whether CCR6⁺ memory T-helper cells producing IL-17A, IL-17F, IL-21, and/or IL-22 are increased in SLE patients and whether this increase is related to the presence of IFN type I signature.

Methods

In total, 25 SLE patients and 15 healthy controls (HCs) were included. SLE patients were divided into IFN type I signature-positive (IFN⁺) (n = 16) and negative (IFN^-) (n = 9) patients, as assessed by mRNA expression of IFN-inducible genes (IFIGs) in monocytes. Expression of IL-17A, IL-17F, IL-21, and IL-22 by CD4⁺CD45RO⁺CCR6⁺ T cells (CCR6⁺ cells) was measured with flow cytometry and compared between IFN⁺, IFN^- patients and HCs.

Results

Increased percentages of IL-17A and IL-17A/IL-17F double-producing CCR6⁺ cells were observed in IFN⁺ patients compared with IFN^- patients and HCs. IL-17A and IL-17F expression within CCR6⁺ cells correlated significantly with IFIG expression. In addition, we found significant correlation between B-cell activating factor of the tumor necrosis family (BAFF)–a factor strongly correlating with IFN type I - and IL-21 producing CCR6⁺ cells.

Conclusions

We show for the first time higher percentages of IL-17A and IL-17A/IL-17F double-producing CCR6⁺ memory T-helper cells in IFN⁺ SLE patients, supporting the hypothesis that IFN type I co-acts with Th17 cytokines in SLE pathogenesis.     

The relationship between lateral meniscus shape and joint contact parameters in the knee: a study using data from the Osteoarthritis Initiative

Introduction

The meniscus has an important role in force transmission across the knee, but a detailed three-dimensional (3D) morphometric shape analysis of the lateral meniscus to elucidate subject-specific function has not been conducted. The aim of this study was to perform 3D morphometric analyses of the lateral meniscus in order to correlate shape variables with anthropometric parameters, thereby gaining a better understanding of the relationship between lateral meniscus shape and its load-bearing function.

Methods

The lateral meniscus (LM) was manually segmented from magnetic resonance images randomly selected from the Osteoarthritis Initiative (OAI) non-exposed control subcohort. A 3D statistical shape model (SSM) was constructed to extract the principal morphological variations (PMV) of the lateral meniscus for 50 subjects (25 male and 25 female). Correlations between the principal morphological variations and anthropometric parameters were tested. Anthropometric parameters that were selected included height, weight, body mass index (BMI), femoral condyle width and axial rotation.

Results

The first principal morphological variation (PMV) was found to correlate with height (r = 0.569), weight (r = 0.647), BMI (r = 0.376), and femoral condyle width (r = 0.622). The third PMV was found to correlate with height (r = 0.406), weight (r = 0.312), and femoral condyle width (r = 0.331). The percentage of the tibial plateau covered by the lateral meniscus decreases as anthropometric parameters relating to size of the subject increase. Furthermore, when the size of the subject increases, the posterior and anterior horns become proportionally longer and wider.

Conclusion

The correlations discovered suggest that variations in meniscal shape can be at least partially explained by the levels of loads transmitted across the knee on a regular basis. Additionally, as the size of the subject increases and body weight rises, the coverage percentage of the meniscus is reduced, suggesting that there would be an increase in the load-bearing by the cartilage. However, this reduced coverage percentage is compensated by the proportionally wider and longer meniscal horn.     

Service Use and Costs for People with Long-Term Neurological Conditions in the First Year following Discharge from In-Patient Neuro-Rehabilitation: A Longitudinal Cohort Study

Background

Knowledge of the configuration and costs of community rehabilitation and support for people with long-term neurological conditions (LTNCs) is needed to inform future service development and resource allocation. In a multicentre prospective cohort study evaluating community service delivery during the year post-discharge from in-patient neuro-rehabilitation, a key objective was to determine service use, costs, and predictors of these costs.

Methods

Patients consecutively admitted over one year to all nine London specialised (Level 1) in-patient neuro-rehabilitation units were recruited on discharge. They or their carers completed postal/web-based questionnaires at discharge and six and twelve months later, providing demographic data and measures of impairment, disability, service needs and provision. This paper describes health and social care service use, informal care and associated costs. Regression models using non-parametric boot-strapping identified predictors of costs over time.

Results

Overall, 152 patients provided consistent data. Mean formal service costs fell significantly from £13,290 (sd £19,369) during the first six months to £9,335 (sd £19,036) from six-twelve months, (t = 2.35, P<0.05), mainly due to declining health service use. At six months, informal care was received on average for 8.2 hours/day, mean cost £14,615 (sd 23,305), comprising 52% of overall care costs. By twelve months, it had increased to 8.8 hours per day, mean cost £15,468 (sd £25,534), accounting for 62% of overall care costs. Being younger and more disabled predicted higher formal care costs, explaining 32% and 30% of the variation in costs respectively at six and twelve months.

Conclusion

Community services for people with LTNCs carry substantial costs that shift from health to social care over time, increasing the burden on families. Prioritising rehabilitation services towards those in greatest need could limit access to others needing on-going support to promote their independence and reduce their reliance on families. This argues for greater investment in future rehabilitation services.     

Activation of triacylglycerol lipase in the fat body of a beetle by adipokinetic hormone

The activation of triacylglycerol lipase and the stimulation of proline synthesis in the fat body of the fruit beetle Pachnoda sinuata by the endogenous octapeptide hormone Melme-CC (pQLNYSPDWa), which belongs to the family of insect adipokinetic hormones, were studied, and the correlation of both events investigated. At rest, the activity of triacylglycerol lipase in the fat body of the beetle was higher than in the fat body of the American cockroach, Periplaneta americana, but lower than in the migratory locust, Locusta migratoria. Triacylglycerol lipase of the beetle is activated by: (a) injection of synthetic Melme-CC and (b) the stimulus of flight. Activation of lipase by Melme-CC is time-dependent. Injection of cpt-cAMP activates triacylglycerol lipase in the fat body and causes an increase in the concentration of proline in the haemolymph at the expense of alanine. In contrast, injection of F-inositol-1,4,5-phosphate does not affect the activation state of lipase, nor the levels of amino acids in the haemolymph. High doses of octopamine do not activate lipase. Furthermore, activity of fat body lipase and proline concentration in the haemolymph both follow a circadian rhythm: both parameters are high in the morning, whereas they are low in the evening. When transfer of Melme-CC, released from the corpora cardiaca, to the thorax/abdomen is prevented by neck-ligation, the activity of lipase, as well as the circulating proline levels are low. Regression analysis revealed that activity of triacylglycerol lipase is positively correlated to proline concentration in the haemolymph, whereas there is a negative correlation of the enzyme activity and alanine level in the haemolymph. From these results we conclude that the activation of fat body triacylglycerol lipase by Melme-CC in P. sinuata stimulates proline synthesis. Proline is one of the major substrates to power flight activity in the beetle.     

Courtship Behavior of Zaprionus indianus (Gupta) (Diptera: Drosophilidae) from Populations Colonizing South America

We describe for the first time the sexual behavior and the courtship song of males of the African fly Zaprionus indianus (Gupta), a recent invader of South America. The male courtship song is formed by monocyclic pulses and the courtship behavior is simple when compared to that of species of Drosophila. Two interpulse interval (IPI) distributions were observed: pre-mounting and mounting. No significant difference was observed between the pre-mounting IPIs of males that descended from three geographical populations from South America. We also observed the songs produced by females and the homosexual behavior exhibited by males. A sequence of bursts is produced by females as a refusal signal against males, while males emit a characteristic song that identifies sex genus, which differs from the courtship song. The short courtship and mating latencies recorded reveal vigorous males and receptive females, respectively.     

Filling of eco-climatological niches in a polyploid complex – A case study in the plant genus Leucanthemum Mill. (Compositae,Anthemideae) from the Iberian Peninsula

In order to assess the effects of polyploidisation on distribution patterns of species in a polyploid complex, we compared potential and actual distribution ranges of representatives from the genus Leucanthemum Mill. (Compositae, Anthemideae), which occur on the Iberian Peninsula with 20 taxa spanning ploidy levels between 2n = 2x = 18 and 2n = 22x = 198. Actual distribution ranges of taxa were derived from geo-referenced herbarium specimens by defining buffer circles around the collection localities to account for geographical uncertainties and haphazardness of specimen collecting. Eco-climatologically potential ranges were modelled with the maximum entropy method (Maxent) based on the actual distributions. By comparison of sizes of realised and eco-climatologically potential areas for each taxon we computed taxon-specific overlap indices that express the filling of eco-climatological niches. The correlation between overlap indices and ploidy levels was tested by Spearman's rank correlation coefficient. We observed a significant negative correlation between ploidy level and sizes of realised distribution ranges and no significant correlation of ploidy level and sizes of potential ranges. Finally, we found that diploid and low-ploidy taxa are filling their potential eco-climatological distribution ranges more exhaustively than highly polyploid taxa. Assuming that ascending polyploidisation is the prevailing mode compared to descending polyploidisation, our results demonstrate that the distribution patterns of members of the Leucanthemum polyploid complex on the Iberian Peninsula are mainly influenced by the age of taxa and not by ecological advantages or disadvantages connected with polyploidy.