Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 μm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 μm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 μm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 μm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced "type 1" and B6.BKS(D)-Lepr db /J "type 2" diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications.diabetes | retina | neurodegeneration | diabetic retinopathy | optical coherence tomography
Summary
The ε4 allele of
APOE
-encoding apolipoprotein (ApoE) is one of the strongest genetic risk factors for Alzheimer’s disease (AD). One of the overarching questions is whether and how this astrocyte-enriched risk factor initiates AD-associated pathology in neurons such as amyloid-β (Aβ) accumulation. Here, we generate neurons and astrocytes from isogenic human induced pluripotent stem cells (hiPSCs) carrying either
APOE
ε3 or
APOE
ε4 allele and investigate the effect of astrocytic ApoE4 on neuronal Aβ production. Secretory factors in conditioned media from ApoE4 astrocytes significantly increased amyloid precursor protein (APP) levels and Aβ secretion in neurons. We further found that increased cholesterol secretion from ApoE4 astrocytes was necessary and sufficient to induce the formation of lipid rafts that potentially provide a physical platform for APP localization and facilitate its processing. Our study reveals the contribution of ApoE4 astrocytes to amyloidosis in neurons by expanding lipid rafts and facilitating Aβ production through an oversupply of cholesterol.
Optical coherence tomography is routinely used clinically for the detection and management of ocular diseases as well as in research where the studies may involve animals. This routine use requires that the developed automated segmentation methods not only be accurate and reliable, but also be adaptable to meet new requirements. We have previously proposed the use of a graph-theoretic approach for the automated 3-D segmentation of multiple retinal surfaces in volumetric human SD-OCT scans. The method ensures the global optimality of the set of surfaces with respect to a cost function. Cost functions have thus far been typically designed by hand by domain experts. This difficult and time-consuming task significantly impacts the adaptability of these methods to new models. Here, we describe a framework for the automated machine-learning based design of the cost function utilized by this graph-theoretic method. The impact of the learned components on the final segmentation accuracy are statistically assessed in order to tailor the method to specific applications. This adaptability is demonstrated by utilizing the method to segment seven, ten and five retinal surfaces from SD-OCT scans obtained from humans, mice and canines, respectively. The overall unsigned border position errors observed when using the recommended configuration of the graph-theoretic method was 6.45 ± 1.87 μm, 3.35 ± 0.62 μm and 9.75 ± 3.18 μm for the human, mouse and canine set of images, respectively.
• Capsule, septum, and T2 hyperintense foci were useful for characterizing large HCC. • Adding ancillary features to enhancement pattern increased accuracy for diagnosing large HCC. • Interobserver agreement was substantial to excellent for ancillary features.
The presented method, initially developed for human OCT, has been adapted for mice, with the potential to be adapted for other animals as well. Quantitative in vivo assessment of the retina in mice allows changes to be measured longitudinally, decreasing the need for them.
Hepatic steatosis assessment is of paramount importance for living liver donor selection because significant hepatic steatosis can affect the postoperative outcome of recipients and the safety of the donor. The validity of various noninvasive imaging methods to assess hepatic steatosis remains controversial. The purpose of our study is to investigate the association between noninvasive imaging methods and pathology to detect steatosis in living liver donors and to propose a prediction model for hepatic steatosis.Liver stiffness measurements (LSMs) and controlled attenuation parameter values in vibration controlled transient elastography, ultrasonography, computed tomography (CT), and magnetic resonance imaging were used as pretransplant screening methods to evaluate living liver donors between 2012 and 2014. Only 1 pathologist assessed tissue sample for hepatic steatosis.The median age of the 79 living donors (53 men and 26 women) was 32 years (16–68 years). The CT liver–spleen attenuation (L–S) difference and the controlled attenuation parameter values were well correlated with the level of hepatic steatosis on liver pathology. Multivariate analysis showed that liver stiffness measurement (LSM) (β 0.903; 95% CI, 0.105–1.702; P = 0.027) and the CT L to S attenuation difference (β = −3.322; 95% CI, −0.502 to −0.142; P = 0.001) were closely associated with hepatic steatosis. We generated the following equation to predict total hepatic steatosis: Hepatic steatosis = 0.903 × LSM – 0.322 × CT L to S attenuation difference (AUC = 86.6% and P = 0.001). The values predicted by the equation correlated well with the presence of hepatic steatosis (r = 0.509 and P < 0.001).The combination of nonenhanced CT L to S attenuation difference and transient elastography using vibration controlled transient elastography provides sufficient information to predict hepatic steatosis in living liver donor candidates.
• The A values of MRI were higher than those of EUS. • The diagnostic accuracies of MRI were higher than those of EUS. • The specificities of MRI were higher than those of EUS.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.