Histological validation of a type 1 diabetes clinical diagnostic model for classification of diabetes.

AIMS: Misclassification of diabetes is common due to an overlap in the clinical features of type 1 and type 2 diabetes. Combined diagnostic models incorporating clinical and biomarker information have recently been developed that can aid classification, but they have not been validated using pancreatic pathology. We evaluated a clinical diagnostic model against histologically defined type 1 diabetes. METHODS: We classified cases from the Network for Pancreatic Organ donors with Diabetes (nPOD) biobank as type 1 (n = 111) or non-type 1 (n = 42) diabetes using histopathology. Type 1 diabetes was defined by lobular loss of insulin-containing islets along with multiple insulin-deficient islets. We assessed the discriminative performance of previously described type 1 diabetes diagnostic models, based on clinical features (age at diagnosis, BMI) and biomarker data [autoantibodies, type 1 diabetes genetic risk score (T1D-GRS)], and singular features for identifying type 1 diabetes by the area under the curve of the receiver operator characteristic (AUC-ROC). RESULTS: Diagnostic models validated well against histologically defined type 1 diabetes. The model combining clinical features, islet autoantibodies and T1D-GRS was strongly discriminative of type 1 diabetes, and performed better than clinical features alone (AUC-ROC 0.97 vs. 0.95; P = 0.03). Histological classification of type 1 diabetes was concordant with serum C-peptide [median < 17 pmol/l (limit of detection) vs. 1037 pmol/l in non-type 1 diabetes; P < 0.0001]. CONCLUSIONS: Our study provides robust histological evidence that a clinical diagnostic model, combining clinical features and biomarkers, could improve diabetes classification. Our study also provides reassurance that a C-peptide-based definition of type 1 diabetes is an appropriate surrogate outcome that can be used in large clinical studies where histological definition is impossible. Parts of this study were presented in abstract form at the Network for Pancreatic Organ Donors Conference, Florida, USA, 19-22 February 2019 and Diabetes UK Professional Conference, Liverpool, UK, 6-8 March 2019.

Does prescribed burning affect leaf secondary metabolites in pine stands?

Prescribed burning (PB) is gaining popularity as a low-cost forest protection measure that efficiently reduces fuel build-up, but its effects on tree health and growth are poorly understood. Here, we evaluated the impact of PB on plant defenses in Mediterranean pine forests (Pinus halepensis and P. nigra ssp. laricio). These chemical defenses were estimated based on needle secondary metabolites (terpenes and phenolics including flavonoids) and discussed in terms of chlorophyll fluorescence and soil nutrients. Three treatments were applied: absence of burning (control plots); single burns (plots burned once); and repeated burns (plots burned twice). For single burns, we also explored changes over time. In P. laricio, PB tended to trigger only minor modifications consisting exclusively of short-lived increases (observed within 3 months after PB) in flavonoid index, possibly due to the leaf temperature increase during PB. In P. halepensis, PB had detrimental effects on physiological performance, consisting of (i) significant decreases in actual PSII efficiency (ΦPSII) in light-adapted conditions after repeated PB, and (ii) short-lived decreases in variable-to-maximum fluorescence ratio (Fv/Fm) after single PB, indicating that PB actually stressed P. halepensis trees. Repeated PB also promoted terpene-like metabolite production, which increased 2 to 3-fold compared to control trees. Correlations between terpene metabolites and soil chemistry were found. These results suggest that PB impacts needle secondary metabolism both directly (via a temperature impact) and indirectly (via soil nutrients), and that these impacts vary according to species/site location, frequency and time elapsed since last fire. Our findings are discussed with regard to the use of PB as a forest management technique and its consequences on plant investment in chemical defenses.

Assessment of the use of biomarkers in aquatic plants for the evaluation of environmental quality: application to seagrasses.

The use of aquatic plants as bio-indicators constitutes an irreplaceable tool for investigation in ecological research, applied to the conservation of littoral ecosystems. Today, studies in both the laboratory and the field have provided encouraging insights into the capacity of aquatic plants to act as biomonitors of environmental quality, through the use of biomarkers, and these are reviewed here. Photosynthetic activity, secondary metabolites, heat shock proteins, enzymes of detoxication, and oxidative stress biomarkers were measured in the case of various stressors, (e.g. light, thermal, hydric/haline stress, or herbicides, metals, organic contaminants). Most of them seem to be valuable and early markers of the environmental conditions, as demonstrated by experimentations carried out on Posidonia oceanica. Nevertheless, none can be in itself a valuable solution, and only a multiparametric approach, including both 'physiological' biomarkers, biomarkers of general stress and more specific biomarkers seems to be appreciable in an ecotoxicological diagnostic.

Effects of mercury on antioxidant mechanisms in the marine phanerogam Posidonia oceanica.

Biochemical markers of oxidative stress such as catalase activity, glutathione S-transferase (GST) activity and levels of lipid peroxidation evaluated in terms of thiobarbituric acid reactive substances (TBARS) were measured in the sheaths of the marine phanerogam Posidonia oceanica (L.) Delile experimentally exposed to 0.01, 0.1 and 1 microgHg l(-1) for 48 h. Up to a threshold concentration of 0.1 microg Hg l(-1), an increase in catalase and GST activities and TBARS levels was observed, indicating that the antioxidant mechanisms were overtaxed and could not prevent membrane lipid peroxidation. Paradoxically, at 1 microg Hg l(-1), the damage seemed to decrease, as the lipid peroxidation levels of exposed sheaths were lower than those of controls and as catalase and GST activities were not different from those of controls. A possible rapid induction of phytochelatins detoxifying mercury could occur at this high level of mercury.