Effects of fecal microbiome transfer in adolescents with obesity: the gut bugs randomized controlled trial

Peer reviewe

Multi-scale, whole-system models of liver metabolic adaptation to fat and sugar in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a serious public health issue associated with high fat, high sugar diets. However, the molecular mechanisms mediating NAFLD pathogenesis are only partially understood. Here we adopt an iterative multi-scale, systems biology approach coupled to in vitro experimentation to investigate the roles of sugar and fat metabolism in NAFLD pathogenesis. The use of fructose as a sweetening agent is controversial; to explore this, we developed a predictive model of human monosaccharide transport, signalling and metabolism. The resulting quantitative model comprising a kinetic model describing monosaccharide transport and insulin signalling integrated with a hepatocyte-specific genome-scale metabolic network (GSMN). Differential kinetics for the utilisation of glucose and fructose were predicted, but the resultant triacylglycerol production was predicted to be similar for monosaccharides; these predictions were verified by in vitro data. The role of physiological adaptation to lipid overload was explored through the comprehensive reconstruction of the peroxisome proliferator activated receptor alpha (PPARα) regulome integrated with a hepatocyte-specific GSMN. The resulting qualitative model reproduced metabolic responses to increased fatty acid levels and mimicked lipid loading in vitro. The model predicted that activation of PPARα by lipids produces a biphasic response, which initially exacerbates steatosis. Our data support the evidence that it is the quantity of sugar rather than the type that is critical in driving the steatotic response. Furthermore, we predict PPARα-mediated adaptations to hepatic lipid overload, shedding light on potential challenges for the use of PPARα agonists to treat NAFLD

Comparison of intima-media thickness and ophthalmic artery resistance index for assessing subclinical atherosclerosis in HIV-1-infected patients

<p>Abstract</p> <p>Background</p> <p>Human immunodeficiency virus (HIV) infection and antiretroviral treatment are associated with metabolic and cardiovascular complications that potentially increase the risk of atherosclerosis and cardiovascular disease in this population. Measurement of arterial wall thickness has been used as a surrogate of extent, severity and progression of atherosclerosis. A cross-sectional cohort study was performed to compare the validity of two non-invasive arterial measures: carotid intima-media thickness (IMT), a parameter of atherosclerosis, and ophthalmic artery resistance index (OARI), an index of occlusive carotid artery disease.</p> <p>Methods</p> <p>A total of 95 patients receiving highly active antiretroviral therapy (HAART) for more than 12 months were consecutively enrolled. IMT and OARI were measured by 7.5 MHz linear probe.</p> <p>Results</p> <p>There was a significant linear increase in IMT and OARI values as the grade of cardiovascular risk (0.70 and 0.69 for very low risk, 0.86 and 0.72 for low risk and 0.98 and 0.74 for medium/high risk, p < 0.001). A IMT > 0.83 and an OARI > 0.72 were the most discriminatory values for predicting a cardiovascular risk ≥ 10% (sensibility 89.6% and 75.8%; sensitivity 70.5% and 68.4%; p < 0.001).</p> <p>Conclusions</p> <p>Our data indicate that OARI may have a potential as a new precocious marker of subclinical atherosclerosis in HIV-1-infected patients.</p

Helminth and Intestinal Protozoa Infections, Multiparasitism and Risk Factors in Champasack Province, Lao People's Democratic Republic

Multiparsitism is a general public health concern in tropical countries, and is of particular importance in the Mekong River basin of Southeast Asia. Here, we report results obtained from an in-depth study of hepato-biliary and intestinal multiparasitism and associated risk factors in three settings of the most southern province of Lao People's Democratic Republic. Multiple species intestinal parasite infections were very common: more than 80% of the study participants harbored at least two and up to seven different intestinal parasites concurrently. Of particular concerns are the high prevalence of the liver fluke Opisthorchis viverrini (64.1%) and the moderate prevalence of the blood fluke Schistosoma mekongi (24.2%), as these fluke infections are responsible for severe hepato-biliary morbidity, including the bile duct cancer cholangiocarcinoma. Hookworm was the most common nematode infection (76.8%). We conclude that given the very high prevalence rates of parasite infections and the extent of multiparasitism, regular deworming is warranted and that this intervention should be coupled with health education and improved assess to clean water and adequate sanitation to consolidate morbidity control and ensure long-term sustainability