Pediatric non alcoholic fatty liver disease: old and new concepts on development, progression, metabolic insight and potential treatment targets

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. NAFLD has emerged to be extremely prevalent, and predicted by obesity and male gender. It is defined by hepatic fat infiltration >5% hepatocytes, in the absence of other causes of liver pathology. It includes a spectrum of disease ranging from intrahepatic fat accumulation (steatosis) to various degrees of necrotic inflammation and fibrosis (non-alcoholic steatohepatatis [NASH]). NAFLD is associated, in children as in adults, with severe metabolic impairments, determining an increased risk of developing the metabolic syndrome. It can evolve to cirrhosis and hepatocellular carcinoma, with the consequent need for liver transplantation. Both genetic and environmental factors seem to be involved in the development and progression of the disease, but its physiopathology is not yet entirely clear. In view of this mounting epidemic phenomenon involving the youth, the study of NAFLD should be a priority for all health care systems. This review provides an overview of current and new clinical-histological concepts of pediatric NAFLD, going through possible implications into patho-physiolocical and therapeutic perspectives

Toll-like receptor-mediated signaling cascade as a regulator of the inflammation network during alcoholic liver disease

Chronic abuse of alcohol leads to various histological abnormalities in the liver. These are conditions collectively known as alcoholic liver disease (ALD). Currently, ALD is considered to be one of the major causes of death worldwide. An impaired intestinal barrier with related endotoxemia is among the various pathogenetic factors. This is mainly characterized by circulating levels of lipopolysaccharide (LPS), considered critical for the onset of intra-hepatic inflammation. This in turn promotes hepatocellular damage and fibrosis in ALD. Elevated levels of LPS exert their effects by binding to Toll-like receptors (TLRs) which are expressed by all liver-resident cells. The activation of TLR signaling triggers an overproduction and release of some cytokines, which promote an autocatalytic cascade of other proinflammatory signals. In this review, we provide an overview of the mechanisms that sustain LPS-mediated activation of TLR signaling, reporting current experimental and clinical evidence of its role during inflammation in ALD

The use of ultrasound in clinical setting for children affected by NAFLD. is it safe and accurate?

Non-alcoholic fatty liver disease (NAFLD) has become over the last decade the most common form of chronic liver disease in children and adults. Thus, establishing the diagnosis of NAFLD is of utmost importance and represents a major challenge as the disease is generally silent and the current gold standard for diagnosis is an invasive liver biopsy, a procedure that is not suitable for screening purposes. Many non-invasive diagnostic tools have been evaluated so far. Recently the utility of ultrasonography for non-invasive diagnosis and estimation of hepatic steatosis has been demonstrated in a large prospective pediatric study

ADAR enzyme and miRNA story: A nucleotide that can make the difference

Adenosine deaminase acting on RNA (ADAR) enzymes convert adenosine (A) to inosine (I) in double-stranded (ds) RNAs. Since Inosine is read as Guanosine, the biological consequence of ADAR enzyme activity is an A/G conversion within RNA molecules. A-to-I editing events can occur on both coding and non-coding RNAs, including microRNAs (miRNAs), which are small regulatory RNAs of ~20-23 nucleotides that regulate several cell processes by annealing to target mRNAs and inhibiting their translation. Both miRNA precursors and mature miRNAs undergo A-to-I RNA editing, affecting the miRNA maturation process and activity. ADARs can also edit 3' UTR of mRNAs, further increasing the interplay between mRNA targets and miRNAs. In this review, we provide a general overview of the ADAR enzymes and their mechanisms of action as well as miRNA processing and function. We then review the more recent findings about the impact of ADAR-mediated activity on the miRNA pathway in terms of biogenesis, target recognition, and gene expression regulation

Antiplane Stoneley waves propagating at the interface between two couple stress elastic materials

We investigate antiplane Stoneley waves, localized at the discontinuity surface between two perfectly bonded half-spaces. Both half-spaces are elastic linear isotropic and possess a microstructure that is described within the theory of couple stress materials with micro-inertia. We show that the microstructure deeply affects wave propagation, which is permitted under broad conditions. This outcome stands in marked contrast to classical elasticity, where antiplane Stoneley waves are not supported and in-plane Stoneley waves exist only under very severe conditions on the material properties of the bonded half-spaces. Besides, Stoneley waves may propagate only beyond a threshold frequency (cuton), for which an explicit expression is provided. For a given frequency above cuton, this expression lends the admissible range of material parameters that allows propagation (passband). In particular, significant contrast between the adjoining materials is possible, provided that Stoneley waves propagate at high enough frequency. Therefore, micro-inertia plays an important role in determining the features of propagation. Considerations concerning existence and uniqueness of antiplane Stoneley waves are given: it is found that evanescent and decaying/exploding modes are also admitted. Results may be especially useful when accounting for the microstructure in non-destructive testing (NDT) and seismic propagation

Classification of Epileptic Activity Through Temporal and Spatial Characterization of Intracranial Recordings

Focal epilepsy is a chronic condition characterized by hyper-activity and abnormal synchronization of a specific brain region. For pharmacoresistant patients, the surgical resection of the critical area is considered a valid clinical solution, therefore, an accurate localization is crucial to minimize neurological damage. In current clinical routine the characterization of the Epileptogenic Zone (EZ) is performed using invasive methods, such as Stereo-ElectroEncephaloGraphy (SEEG). Medical experts perform the tag of neural electrophysiological recordings by visually inspecting the acquired data, a highly time consuming and subjective procedure. Here we show the results of an automatic multi-modal classification method for the evaluation of critical areas in focal epileptic patients. The proposed method represents an attempt in the characterization of brain areas which integrates the anatomical information on neural tissue, inferred using Magnetic Resonance Imaging (MRI) in combination with spectral features extracted from SEEG recordings

Influence of severe thermal preconditioning on the bond between carbon FRCM and masonry substrate: Effect of textile pre-impregnation

Fabric-reinforced cementitious matrix (FRCM) composites often include polymer-impregnated bundles to improve the exploitation of the textile mechanical properties. However, organic components may degrade when exposed to elevated temperature. In this paper, the bond behavior of a carbon FRCM applied to a masonry substrate and exposed to a thermal preconditioning up to 300 °C for 250 min is investigated. Tensile tests on the textile and flexural and compression tests on the mortar matrix, as well as single-lap direct shear tests of FRCM-masonry joints with bare and impregnated textiles, are performed. Results show that the polymeric impregnation improves the mechanical properties of the FRCM even after thermal preconditioning

Bifidobacteria and lactobacilli in the gut microbiome of children with non-alcoholic fatty liver disease: which strains act as health players?

Introduction: Non-alcoholic fatty liver disease (NAFLD), considered the leading cause of chronic liver disease in children, can often progress from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It is clear that obesity is one of the main risk factors involved in NAFLD pathogenesis, even if specific mechanisms have yet to be elucidated. We investigated the distribution of intestinal bifidobacteria and lactobacilli in the stools of four groups of children: obese, obese with NAFL, obese with NASH, and healthy, age-matched controls (CTRLs). Material and methods: Sixty-one obese, NAFL and NASH children and 54 CTRLs were enrolled in the study. Anthropometric and metabolic parameters were measured for all subjects. All children with suspected NASH underwent liver biopsy. Bifidobacteria and lactobacilli were analysed in children’s faecal samples, during a broader, 16S rRNA-based pyrosequencing analysis of the gut microbiome. Results: Three Bifidobacterium spp. (Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium adolescentis) and five Lactobacillus spp. (L. zeae, L. vaginalis, L. brevis, L. ruminis, and L. mucosae) frequently recurred in metagenomic analyses. Lactobacillus spp. increased in NAFL, NASH, or obese children compared to CTRLs. Particularly, L. mucosae was significantly higher in obese (p = 0.02426), NAFLD (p = 0.01313) and NASH (p = 0.01079) than in CTRLs. In contrast, Bifidobacterium spp. were more abundant in CTRLs, suggesting a protective and beneficial role of these microorganisms against the aforementioned diseases. Conclusions: Bifidobacteria seem to have a protective role against the development of NAFLD and obesity, highlighting their possible use in developing novel, targeted and effective probiotics

Paediatric non-alcoholic fatty liver disease: impact on patients and mothers' quality of life

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the causes of fatty liver in adults and is currently the primary form of chronic liver disease in children and adolescents. However, the psychological outcome (i.e. the behavioural problems that can in turn be related to psychiatric conditions, like anxiety and mood disorders, or lower quality of life) in children and adolescents suffering of NAFLD has not been extensively explored in the literature. Objectives: The present study aims at evaluating the emotional and behavioural profile in children suffering from NAFLD and the quality of life in their mothers. Patients and Methods: A total of 57 children (18 females/39 males) with NAFLD were compared to 39 age-matched control children (25 females/14 males). All participants were submitted to the following psychological tools to assess behavior, mood, and anxiety: the Multidimensional Anxiety Scale for Children (MASC), the Child Behavior Checklist (CBCL), and the Children's Depression Inventory (CDI). Moreover, the mothers of 40 NAFLD and 39 control children completed the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire. Results: NAFLD children scored significantly higher as compared to control children in MASC (P = 0.001) and CDI total (P < 0.001) scales. The CBCL also revealed significantly higher scores for NAFLD children in total problems (P = 0.046), internalizing symptoms (P = 0.000) and somatic complaints (P < 0.001). The WHOQOL-BREF revealed significantly lower scores for the mothers of NAFLD children in the overall perception of the quality of life (P < 0.001), and in the "relationships" domain (P = 0.023). Conclusions: Increased emotional and behavioural problems were detected in children with NAFLD as compared to healthy control children, together with an overall decrease in their mothers' quality of life. These results support the idea that these patients may benefit from a psychological intervention, ideally involving both children and parents, whose quality of life is likely negatively affected by this disease