Azole resistance is evolving and growing in frequency. Established and novel mechanisms may be responsible.

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Aspergillus niger is a common clinical isolate. Multiple species comprise the Aspergillus section Nigri and are separable using sequence data. The antifungal susceptibility of these cryptic species is not known. We determined the azole MICs of 50 black aspergilli, 45 from clinical specimens, using modified EUCAST (mEUCAST) and Etest methods. Phylogenetic trees were prepared using the internal transcribed spacer, beta-tubulin, and calmodulin sequences to identify strains to species level and the results were compared with those obtained with cyp51A sequences. We attempted to correlate cyp51A mutations with azole resistance. Etest MICs were significantly different from mEUCAST MICs (P < 0.001), with geometric means of 0.77 and 2.79 mg/liter, respectively. Twenty-six of 50 (52%) isolates were itraconazole resistant by mEUCAST (MICs > 8 mg/liter), with limited cross-resistance to other azoles. Using combined beta-tubulin/calmodulin sequences, the 45 clinical isolates grouped into 5 clades, A. awamori (55.6%), A. tubingensis (17.8%), A. niger (13.3%), A. acidus (6.7%), and an unknown group (6.7%), none of which were morphologically distinguishable. Itraconazole resistance was found in 36% of the isolates in the A. awamori group, 90% of the A. tubingensis group, 33% of the A. niger group, 100% of the A. acidus group, and 67% of the unknown group. These data suggest that cyp51A mutations in section Nigri may not play as important a role in azole resistance as in A. fumigatus, although some mutations (G427S, K97T) warrant further study. Numerous cryptic species are found in clinical isolates of the Aspergillus section Nigri and are best reported as "A. niger complex" by clinical laboratories. Itraconazole resistance was common in this data set, but azole cross-resistance was unusual. The mechanism of resistance remains obscure.

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We describe a novel method of estimating reduced bone mineral density (BMD) from dental panoramic tomograms (DPTs), which show the entire mandible. Careful expert width measurement of the inferior mandibular cortex has been shown to be predictive of BMD in hip and spine osteopenia and osteoporosis. We have implemented a method of automatic measurement of the width by active shape model search, using as training data 132 DPTs of female subjects whose BMD has been established by dual-energy X-ray absorptiometry. We demonstrate that widths measured after fully automatic search are significantly correlated with BMD, and exhibit less variability than manual measurements made by different experts. The correlation is highest towards the lateral region of the mandible, in a position different from that previously employed for manual width measurement. An receiver-operator characterstic (ROC) analysis for identifying osteopenia (T < -1: BMD more than one standard deviation below that of young healthy females) gives an area under curve (AUC) value of 0.64. Using a minimal interaction to initiate active shape model (ASM) search, the measurement can be made at the optimum region of the mandible, resulting in an AUC value of 0.71. Using an independent test set, AUC for detection of osteoporosis (T < -2.5) is 0.81.

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SSc is a chronic multi-system disease with wide-reaching consequences. Gastrointestinal features are present in over 90% of cases and these, together with other disease manifestations, may lead to nutritional decline. This produces substantial morbidity, including reliance on enteral support and even parenteral nutrition-dependent intestinal failure. These complications carry an associated mortality. Up to 18% of patients with SSc are reported to be at high risk of malnutrition [as assessed by Malnutrition Universal Screening Tool (MUST) criteria], with risk increasing with disease severity. Little is known about this decline, its rate of progression and how it affects the individual. Few case series report on nutritional interventions. Most current interventions are based on experience in other diseases. The development of specialist knowledge of SSc-related gastrointestinal disease management and nutritional screening and interventions is required. This paper reviews current knowledge relating to malnutrition and its management in SSc.