Statins and non-alcoholic fatty liver disease

Dear Editor, In April 9 issue, van den Berg et al1 report interesting results on the indication for lipid‐lowering treatment in a large cohort with suspected non‐alcoholic fatty liver disease (NAFLD) within the population‐based Lifelines Cohort Study. Fatty liver index (FLI) ≥60 was used as a proxy of NAFLD and the NAFLD fibrosis score (NFS) to identify the NAFLD patients with suspected advanced fibrosis. Cardiovascular disease (CVD) risk was established by the 2016 European society of Cardiology/European Atherosclerosis Society (ESC/EAS) Guidelines for the Management of Dyslipidemias.2 Subjects with FLI ≥ 60 (suspected NAFLD) had an increased 10‐ year predicted cardiovascular risk compared to those with FLI < 60 with an approximately 2 times higher need for statin therapy based on CVD risk prediction and their LDL cholesterol level. Subjects with a FLI ≥ 60 were more likely to be classified with type 2 diabetes, Metabolic Syndrome (MetS), history of CVD and impaired renal function. Interestingly, estimated 10‐year very high cardiovascular risk was approximately 4 times higher in subjects with a NFS > 0.676 compared to those with the absence of advanced fibrosis. Finally, indication for statin treatment was positively associated with a FLI ≥ 60 after controlling for age, sex, current smoking, impaired renal function, and the presence of MetS and its individual components. The above results have an even greater relevance if we consider that all the subjects who were already on statin therapy were subtracted from the analysis. These findings may have an important clinical relevance and emphasize the need for effective treatment with statins in patients with NAFLD. Indeed, accumulating evidence suggests that CVD, rather than liver disease, dictates the outcomes in NAFLD.3 Besides, in most subjects NAFLD constitutes the hepatic component of MetS and numerous patients have atherogenic dyslipidemia. This study further supports the results of a previous study by our group where under prescription of statins in patients with NAFLD was observed.4 In fact, mild liver enzyme elevation remains a concern and despite its proven efficacy and safety,5 statin administration is sometimes limited by the worry about related side effects. Indeed, there is a tendency of general physicians to discourage statin use in patients with baseline elevation of serum liver enzymes and/ or to discontinue medication when minor alterations were appreciated. Of note, in our study, statin under‐use was high also in patients at very high CV risk such as those with a previous CV event. This study by van den Berg et al further stresses the issue of under prescription of statins in people with NAFLD and indication for treatment, based on CV risk class and low‐density lipoprotein cholesterol target according to ESC/EAS guidelines

Un "Marte razionale"? Bartolomeo D'Alviano lettore dei classici

The birth of the so called \u2018\u2018Marte razionale\u2019\u2019 has been collocated in the milieu of commander in chief of Venetian army Francesco Maria I Della Rovere around 1530 and Bartolomeo d\u2019Alviano was considered a forerunner for his well known expertise in fortifications and territorial asset. Alviano in early 16th century started to transform Venetian army on a regular basis of study on classical writers as Vegetius, Aelian, Sallust and probably the group of humanists who surrounded him \u2013 among the others Andrea Navagero, Gerolamo Borgia and Giovanni Cotta \u2013 supported him in this try

Using GANs to Create Training Images for Object Pose Estimation

openObject pose estimation is a significant challenge in computer vision, involving determining the position and orientation of an object within an image. This task requires a large training dataset representing various poses of the object. However, collecting such data can be costly and labor-intensive. This thesis examines the architecture of Generative Adversarial Networks (GANs), which can generate realistic images from random noise, and aims to study various GAN architectures and apply them to generate images that can be used in object pose estimation. Throughout the experiments, pre-rendered images of the Cat's model from LINEMOD [1] will serve as input to the considered GAN models, aiming to reproduce realistic images containing the reference Cat in the same predefined pose. First, a Domain Adaptation (DA) approach has been used to generate underwater images based on an unpaired dataset. This experiment served as a proof-of-concept to illustrate the process of generating images in environments where data collection is notably challenging. Next, the focus has been shifted to generating new samples from the LINEMOD's dataset. Here, the objective is to capture features and spatial relationships between objects from the real images and use them to generate new pictures coherent with the input Cat's model. Finally, the best GAN models have been combined with Pixel-wise Voting Network (PVNet [2]) to compare their performance against the PVNet model trained using the conventional image Superimposing Method (PVNet-SM). The main conclusion of this work is that GANs can achieve similar performance as PVNet-SM while eliminating the need for manual work in background selection and dataset preparation. [1] S. Hinterstoisser, V. Lepetit, S. Ilic, et al., "Model-based training, detection, and pose estimation of texture-less 3D objects in heavily cluttered scenes," in Computer Vision ACCV 2012, K. M. Lee, Y. Matsushita, J. M. Rehg, and Z. Hu, Eds., vol. 7724, Springer Berlin Heidelberg, 2012, pp. 548–562. [2] S. Peng, Y. Liu, Q. Huang, X. Zhou, and H. Bao, "PVNet: Pixel-wise voting network for 6-DOF pose estimation," in Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR), 2019.Object pose estimation is a significant challenge in computer vision, involving determining the position and orientation of an object within an image. This task requires a large training dataset representing various poses of the object. However, collecting such data can be costly and labor-intensive. This thesis examines the architecture of Generative Adversarial Networks (GANs), which can generate realistic images from random noise, and aims to study various GAN architectures and apply them to generate images that can be used in object pose estimation. Throughout the experiments, pre-rendered images of the Cat's model from LINEMOD [1] will serve as input to the considered GAN models, aiming to reproduce realistic images containing the reference Cat in the same predefined pose. First, a Domain Adaptation (DA) approach has been used to generate underwater images based on an unpaired dataset. This experiment served as a proof-of-concept to illustrate the process of generating images in environments where data collection is notably challenging. Next, the focus has been shifted to generating new samples from the LINEMOD's dataset. Here, the objective is to capture features and spatial relationships between objects from the real images and use them to generate new pictures coherent with the input Cat's model. Finally, the best GAN models have been combined with Pixel-wise Voting Network (PVNet [2]) to compare their performance against the PVNet model trained using the conventional image Superimposing Method (PVNet-SM). The main conclusion of this work is that GANs can achieve similar performance as PVNet-SM while eliminating the need for manual work in background selection and dataset preparation. [1] S. Hinterstoisser, V. Lepetit, S. Ilic, et al., "Model-based training, detection, and pose estimation of texture-less 3D objects in heavily cluttered scenes," in Computer Vision ACCV 2012, K. M. Lee, Y. Matsushita, J. M. Rehg, and Z. Hu, Eds., vol. 7724, Springer Berlin Heidelberg, 2012, pp. 548–562. [2] S. Peng, Y. Liu, Q. Huang, X. Zhou, and H. Bao, "PVNet: Pixel-wise voting network for 6-DOF pose estimation," in Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR), 2019

The Ljapunov-Schmidt reduction for some critical problems

This is a survey about the application of the Ljapunov-Schmidt reduction for some critical problems

Reduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?

Lysosomal acid lipase (LAL) plays a key role in intracellular lipid metabolism. Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage, as observed in two recessive autosomal genetic diseases, Wolman disease and Cholesterol ester storage disease. Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency. By contrast, few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene. In the last few years, a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease (NAFLD), suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease. Patients with NAFLD show a significant, progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis. Among cirrhosis of different etiologies, those with cryptogenic cirrhosis show the most significant reductions of LAL activity. These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD. Moreover, the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting

Oxidative stress: new insights on the association of nonalcoholic fatty liver disease and atherosclerosis

Non-alcoholic fatty liver disease (NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseases ranging from simple fatty liver to non-alcoholic steatohepatitis (NASH), which may progress to fibrosis and more severe liver complications such as cirrhosis, hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity, insulin resistance, hypertension, and dyslipidaemia, and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and, to a lesser extent, to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus, oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed, with conflicting results. In particular, vitamin E supplementation has been suggested for the treatment of non-diabetic, non-cirrhotic adults with active NASH, although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol, silybin, L-carnitine and pentoxiphylline. No trial so far, has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New, large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed

TEM study of homoepitaxial diamond layers scheduled for high power devices: FIB method of sample preparation

Homoepitaxial diamond structure observation by transmission electron microscopy (TEM) is still a very hard job due to the difficulty in preparing electron transparent samples for the further observation. The present contribution details the experimental operations with their respective conditions step by step. Finally high resolution TEM (HREM) observations of a CVD grown epilayer on a unnintentionally doped HPHT (001) oriented substrate are present to show the high quality of the sample preparation method.4 page

Multi-bubble nodal solutions for slightly subcritical elliptic problems in domains with symmetries

We study the existence of sign-changing solutions with multiple bubbles to the slightly subcritical problem -\Delta u=|u|^{2^*-2-\e}u \hbox{in}\Omega, \quad u=0 \hbox{on}\partial \Omega, where $\Omega$ is a smooth bounded domain in $\R^N$, $N\geq 3$, $2^*=\frac{2N}{N-2}$ and \e>0 is a small parameter. In particular we prove that if $\Omega$ is convex and satisfies a certain symmetry, then a nodal four-bubble solution exists with two positive and two negative bubbles