A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence

Non-Alcoholic Fatty Liver Disease (NAFLD) is now the most prevalent form of chronic liver disease, affecting 10%–20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation of more widespread metabolic dysfunction and is strongly associated with a number of metabolic risk factors, including insulin resistance, dyslipidaemia, cardiovascular disease and, most significantly, obesity. Despite this, ”paediatric” NAFLD remains under-studied, under-recognised and, potentially, undermanaged. This article will explore and evaluate our current understanding of NAFLD in childhood and adolescence and how it differs from adult NAFLD, in terms of its epidemiology, pathophysiology, natural history, diagnosis and clinical management. Given the current absence of definitive radiological and histopathological diagnostic tests, maintenance of a high clinical suspicion by all members of the multidisciplinary team in primary and specialist care settings remains the most potent of diagnostic tools, enabling early diagnosis and appropriate therapeutic intervention

Fat-to-glucose interconversion by hydrodynamic transfer of two glyoxylate cycle enzyme genes

The glyoxylate cycle, which is well characterized in higher plants and some microorganisms but not in vertebrates, is able to bypass the citric acid cycle to achieve fat-to-carbohydrate interconversion. In this context, the hydrodynamic transfer of two glyoxylate cycle enzymes, such as isocytrate lyase (ICL) and malate synthase (MS), could accomplish the shift of using fat for the synthesis of glucose. Therefore, 20 mice weighing 23.37 ± 0.96 g were hydrodinamically gene transferred by administering into the tail vein a bolus with ICL and MS. After 36 hours, body weight, plasma glucose, respiratory quotient and energy expenditure were measured. The respiratory quotient was increased by gene transfer, which suggests that a higher carbohydrate/lipid ratio is oxidized in such animals. This application could help, if adequate protocols are designed, to induce fat utilization for glucose synthesis, which might be eventually useful to reduce body fat depots in situations of obesity and diabetes

Multi-Objective Big Data Optimization with jMetal and Spark

Big Data Optimization is the term used to refer to optimization problems which have to manage very large amounts of data. In this paper, we focus on the parallelization of metaheuristics with the Apache Spark cluster computing system for solving multi-objective Big Data Optimization problems. Our purpose is to study the influence of accessing data stored in the Hadoop File System (HDFS) in each evaluation step of a metaheuristic and to provide a software tool to solve these kinds of problems. This tool combines the jMetal multi-objective optimization framework with Apache Spark. We have carried out experiments to measure the performance of the proposed parallel infrastructure in an environment based on virtual machines in a local cluster comprising up to 100 cores. We obtained interesting results for computational e ort and propose guidelines to face multi-objective Big Data Optimization problems.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Bariatric surgery as a treatment for metabolic syndrome

Obesity is the pandemic of the 21st century. Obesity comorbidities, including hypertension, dyslipidaemia and glucose intolerance define metabolic syndrome, which increases mortality risk and decreases the quality of life. Compared with lifestyles (diet and physical activity) and pharmacological interventions, bariatric surgery is by far the most effective treatment for obesity and its comorbidities. This minimally invasive surgical treatment is based on an increase of satiety (by hormonal regulation and decreasing stomach volume) or a decrease in nutrient retention (gastric and/or intestinal resection). Bariatric surgery has widely demonstrated a beneficial effect on excess body weight loss, cardiovascular risk, dyslipidaemia, non-alcoholic fatty liver disease or glucose homeostasis, among other obesity-related metabolic diseases. This review describes current efforts for the implementation of bariatric surgery in metabolic syndrome, which are mainly focused on the formulation of key definition criteria for targeting the most suitable population for this therapeutic approach. Patients should undergo appropriate nutritional and psychological follow up in order to achieve and maintain weight loss milestones and a healthy metabolic status

Ethnic differences and heterogeneity in genetic and metabolic makeup contributing to nonalcoholic fatty liver disease

Obesity is the most prevalent noncommunicable disease in the 21st century, associated with triglyceride deposition in hepatocytes leading to nonalcoholic fatty liver disease (NAFLD). NAFLD is now present in around a third of the world's population. Epidemiological studies have concluded that ethnicity plays a role in complications and treatment response. However, definitive correlations of ethnicity with NAFLD are thoroughly under-reported. A comprehensive review was conducted on ethnic variation in NAFLD patients and its potential role as a crucial effector in complications and treatment response. The highest NAFLD prevalence is observed in Hispanic populations, exhibiting a worse disease progression. In contrast, African-Caribbeans exhibit the lowest risk, with less severe steatosis and inflammation, lower levels of triglycerides, and less metabolic derangement, but conversely higher prevalence of insulin resistance. The prevalence of NAFLD in Asian cohorts is under-reported, although reaching epidemic proportions in these populations. The most well-documented NAFLD patient population is that of Caucasian ethnicity, especially from the US. The relative paucity of available literature suggests there is a vital need for more large-scale multi-ethnic clinical cohort studies to determine the incidence of NAFLD within ethnic groups. This would improve therapy and drug development, as well as help identify candidate gene mutations which may differ within the population based on ethnic background

Acetylcholine induces fibrogenic effects via M2/M3 ACh receptors in NASH and in primary human hepatic stellate cells

BACKGROUND: The parasympathetic nervous system (PNS), via neurotransmitter Acetylcholine (ACh), modulates fibrogenesis in animal models. However, the role of ACh in human hepatic fibrogenesis is unclear. AIMS: We aimed to determine the fibrogenic responses of human hepatic stellate cells (hHSC) to ACh and the relevance of the PNS in hepatic fibrosis in patients with non-alcoholic steatohepatitis (NASH). METHODS: Primary hHSC were analysed for synthesis of endogenous ACh and acetylcholinesterase (AChE), and gene expression of choline acetyltransferase (ChAT) and muscarinic acetylcholine receptors (mAChR). Cell proliferation and fibrogenic markers were analysed in hHSC exposed to ACh, Atropine (Atrop), Mecamylamine (Mec), methoctramine and 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP). MAChR expression was analysed in human NASH scored for fibrosis. RESULTS: We observed that hHSC synthesise ACh and AChE, and express ChAT and M1-M5 mAChR. We also show that M2 was increased during NASH progression, while both M2 and M3 were found upregulated in activated hHSC. Furthermore, endogenous ACh is required for hHSC basal growth. Exogenous ACh resulted in hHSC hyperproliferation via mAChR and PI-3 K and MEK signalling pathways, as well as increased fibrogenic markers. CONCLUSION: We show that ACh regulates hHSC activation via M2 and M3 mAChR involving the PI-3 K and MEK pathways in vitro. Finally, we provide evidence that the PNS may be involved in human NASH fibrosis

Connection Between Type A and E Factorizations and Construction of Satellite Algebras

Recently, we introduced a new class of symmetry algebras, called satellite algebras, which connect with one another wavefunctions belonging to different potentials of a given family, and corresponding to different energy eigenvalues. Here the role of the factorization method in the construction of such algebras is investigated. A general procedure for determining an so(2,2) or so(2,1) satellite algebra for all the Hamiltonians that admit a type E factorization is proposed. Such a procedure is based on the known relationship between type A and E factorizations, combined with an algebraization similar to that used in the construction of potential algebras. It is illustrated with the examples of the generalized Morse potential, the Rosen-Morse potential, the Kepler problem in a space of constant negative curvature, and, in each case, the conserved quantity is identified. It should be stressed that the method proposed is fairly general since the other factorization types may be considered as limiting cases of type A or E factorizations.Comment: 20 pages, LaTeX, no figure, to be published in J. Phys.

ICTD Work, Plus mFeel : improving communication in resource-poor settings

This issue's Works-In-Progress department has four entries related to the issue's theme, Information and Communication Technologies for Development (ICTD). They are “Sustainable ICT in Agricultural Value Chains”, “Measuring Social Inclusion in Primary Schools”, “An Architecture for Green Mobile Computation”, and “Improving Communication in Resource-Poor Settings”. A fifth entry, “mFeel: An Affective Mobile System”, covers the mFeel mobile system, which combines context awareness with affective and cognitive techniques

Movement variability in stroke patients and controls performing two upper limb functional tasks: a new assessment methodology

Background: In the evaluation of upper limb impairment post stroke there remains a gap between detailed kinematic analyses with expensive motion capturing systems and common clinical assessment tests. In particular, although many clinical tests evaluate the performance of functional tasks, metrics to characterise upper limb kinematics are generally not applicable to such tasks and very limited in scope. This paper reports on a novel, user-friendly methodology that allows for the assessment of both signal magnitude and timing variability in upper limb movement trajectories during functional task performance. In order to demonstrate the technique, we report on a study in which the variability in timing and signal magnitude of data collected during the performance of two functional tasks is compared between a group of subjects with stroke and a group of individually matched control subjects. Methods: We employ dynamic time warping for curve registration to quantify two aspects of movement variability: 1) variability of the timing of the accelerometer signals' characteristics and 2) variability of the signals' magnitude. Six stroke patients and six matched controls performed several trials of a unilateral ('drinking') and a bilateral ('moving a plate') functional task on two different days, approximately 1 month apart. Group differences for the two variability metrics were investigated on both days. Results: For 'drinking from a glass' significant group differences were obtained on both days for the timing variability of the acceleration signals' characteristics (p = 0.002 and p = 0.008 for test and retest, respectively); all stroke patients showed increased signal timing variability as compared to their corresponding control subject. 'Moving a plate' provided less distinct group differences. Conclusion: This initial application establishes that movement variability metrics, as determined by our methodology, appear different in stroke patients as compared to matched controls during unilateral task performance ('drinking'). Use of a user-friendly, inexpensive accelerometer makes this methodology feasible for routine clinical evaluations. We are encouraged to perform larger studies to further investigate the metrics' usefulness when quantifying levels of impairment

Computer Simulation of Cellular Patterning Within the Drosophila Pupal Eye

We present a computer simulation and associated experimental validation of assembly of glial-like support cells into the interweaving hexagonal lattice that spans the Drosophila pupal eye. This process of cell movements organizes the ommatidial array into a functional pattern. Unlike earlier simulations that focused on the arrangements of cells within individual ommatidia, here we examine the local movements that lead to large-scale organization of the emerging eye field. Simulations based on our experimental observations of cell adhesion, cell death, and cell movement successfully patterned a tracing of an emerging wild-type pupal eye. Surprisingly, altering cell adhesion had only a mild effect on patterning, contradicting our previous hypothesis that the patterning was primarily the result of preferential adhesion between IRM-class surface proteins. Instead, our simulations highlighted the importance of programmed cell death (PCD) as well as a previously unappreciated variable: the expansion of cells' apical surface areas, which promoted rearrangement of neighboring cells. We tested this prediction experimentally by preventing expansion in the apical area of individual cells: patterning was disrupted in a manner predicted by our simulations. Our work demonstrates the value of combining computer simulation with in vivo experiments to uncover novel mechanisms that are perpetuated throughout the eye field. It also demonstrates the utility of the Glazier–Graner–Hogeweg model (GGH) for modeling the links between local cellular interactions and emergent properties of developing epithelia as well as predicting unanticipated results in vivo