Improved predictive diagnosis of diabetic macular edema based on hybrid models: An observational study.

Diabetic Macular Edema (DME) is the most common sight-threatening complication of type 2 diabetes. Optical Coherence Tomography (OCT) is the most useful imaging technique to diagnose, follow up, and evaluate treatments for DME. However, OCT exam and devices are expensive and unavailable in all clinics in low- and middle-income countries. Our primary goal was therefore to develop an alternative method to OCT for DME diagnosis by introducing spectral information derived from spontaneous electroretinogram (ERG) signals as a single input or combined with fundus that is much more widespread. Baseline ERGs were recorded in 233 patients and transformed into scalograms and spectrograms via Wavelet and Fourier transforms, respectively. Using transfer learning, distinct Convolutional Neural Networks (CNN) were trained as classifiers for DME using OCT, scalogram, spectrogram, and eye fundus images. Input data were randomly split into training and test sets with a proportion of 80 %-20 %, respectively. The top performers for each input type were selected, OpticNet-71 for OCT, DenseNet-201 for eye fundus, and non-evoked ERG-derived scalograms, to generate a combined model by assigning different weights for each of the selected models. Model validation was performed using a dataset alien to the training phase of the models. None of the models powered by mock ERG-derived input performed well. In contrast, hybrid models showed better results, in particular, the model powered by eye fundus combined with mock ERG-derived information with a 91 % AUC and 86 % F1-score, and the model powered by OCT and mock ERG-derived scalogram images with a 93 % AUC and 89 % F1-score. These data show that the spontaneous ERG-derived input adds predictive value to the fundus- and OCT-based models to diagnose DME, except for the sensitivity of the OCT model which remains the same. The inclusion of mock ERG signals, which have recently been shown to take only 5 min to record in daylight conditions, therefore represents a potential improvement over existing OCT-based models, as well as a reliable and cost-effective alternative when combined with the fundus, especially in underserved areas, to predict DME.

Oxidative stress caused by ozone exposure induces ß-amyloid 1-42 overproduction and mitochondrial accumulation by activating the amyloidogenic pathway.

Oxidative stress is a major risk factor for Alzheimer's disease (AD) that has been suggested to be the trigger of AD pathology. However, whether oxidative damage precedes and contributes directly to the intracellular accumulation of beta amyloid 1-42 (ßA42) peptide remains a matter of debate. Chronic exposure to low doses of ozone similar to the levels during a day of high pollution in México City causes a state of oxidative stress that elicits progressive neurodegeneration in the hippocampi of rats. Several reports have demonstrated that the mitochondria are among the first organelles to be affected by oxidative stress and ßA42 toxicity and act as sites of the accumulation of ßA42, which affects energy metabolism. However, the mechanisms related to the neurodegeneration process and organelle damage that occur in conditions of chronic exposure to low doses of ozone have not been demonstrated. To analyze the effect of chronic ozone chronic exposure on changes in the production and accumulation of the ßA42 and ßA40 peptides in the mitochondria of hippocampal neurons of rats exposed to ozone, we examined the mitochondrial expression levels of Presenilins 1 and 2 and ADAM10 to detect changes related to the oxidative stress caused by low doses of ozone (0.25ppm). The results revealed significant accumulations of ßA42 peptide in the mitochondrial fractions on days 60 and 90 of ozone exposure along with reductions in beta amyloid 1-40 accumulation, significant overexpressions of Pres2 and significant reductions in ADAM10 expression. Beta amyloid immunodetection revealed that there were some intracellular deposits of ßA42 and that ßA42 and the mitochondrial markers OPA1 and COX1 colocalized. These results indicate that the time of exposure to ozone and the accumulation of ßA42 in the mitochondria of the hippocampal cells of rats were correlated. Our results suggest that the accumulation of the ßA42 peptide may promote mitochondrial dysfunction due to its accumulation and overproduction.