Non-alcoholic fatty liver disease: relationship with cardiovascular risk markers and clinical endpoints

Non-alcoholic fatty liver disease (NAFLD) is a common diagnosis and is increasing in prevalence worldwide. NAFLD is usually asymptomatic at presentation; progression of the disease is unpredictable, leading to the development of a variety of techniques for screening, diagnosis and risk stratification. Clinical methods in current use include serum biomarker panels, hepatic ultrasound, magnetic resonance imaging, and liver biopsy. NAFLD is strongly associated with the metabolic syndrome, and the most common cause of death for people with the condition is cardiovascular disease. Whether NAFLD is an independent cardiovascular risk factor needs exploration. NAFLD has been associated with surrogate markers of cardiovascular disease such as carotid intima-media thickness, the presence of carotid plaque, brachial artery vasodilatory responsiveness and CT coronary artery calcification score. There is no effective medical treatment for NAFLD and evidence is lacking regarding the efficacy of interventions in mitigating cardiovascular risk. Health care professionals managing patients with NAFLD should tackle the issue with early identification of risk factors and aggressive modification. Current management strategies therefore comprise lifestyle change,with close attention to known cardiovascular risk factors

Liver fat in adults with GH deficiency: comparison to matched controls and the effect of GH replacement

CONTEXT: Existing data regarding the association between growth hormone deficiency (GHD) and liver fat content are conflicting. OBJECTIVE: We aimed i) to assess intrahepatocellular lipid (IHCL) content in hypopituitary adults with GHD compared to matched controls and ii) to evaluate the effect of growth hormone (GH) replacement on IHCL content. DESIGN: Cross-sectional comparison and controlled intervention study. PATIENTS, PARTICIPANTS: Cross-sectional comparison: 22 hypopituitary adults with GHD and 44 healthy controls matched for age, BMI, gender and ethnicity. Intervention study: 9 GHD patients starting GH replacement (GH Rx group), 9 GHD patients not starting replacement therapy (non-GH Rx group). INTERVENTION: Intervention study:GH replacement for 6 months in the GH Rx group, dosage was titrated to achieve normal IGF-1 levels. MAIN OUTCOME MEASURES: IHCL content determined by proton magnetic resonance spectroscopy (1 H MRS). RESULTS: Cross-sectional comparison: There was no difference in IHCL content between GHD patients and healthy controls (1.89% (0.30, 4.03) vs. 1.14% (0.22, 2.32); p=0.2), the prevalence of patients with hepatic steatosis (IHCL of ≥ 5.56%) was similar in the two groups (22.7% vs. 15.9%; chi square probability = 0.4). Intervention study: The change in IHCL content over 6 months did not differ between the GH Rx group and the non-GH Rx group (-0.63 ± 4.53% vs. +0.11 ± 1.46%; p=0.6). CONCLUSIONS: In our study liver fat content and the prevalence of hepatic steatosis did not differ between hypopituitary adults with GHD and matched controls. In GHD patients GH replacement had no effect on liver fat content

Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis

Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated with increasing hepatic steatosis. The genotype-specific lipid disturbances may shed light on genotypic variations in liver disease progression and promotion of hepatocellular cancer in HCV-G3

Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis

Background: Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. Aims: We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. Methods: We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. Results: HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. Conclusions: We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated with increasing hepatic steatosis. The genotype-specific lipid disturbances may shed light on genotypic variations in liver disease progression and promotion of hepatocellular cancer in HCV-G3

On equations over sets of integers

Systems of equations with sets of integers as unknowns are considered. It is shown that the class of sets representable by unique solutions of equations using the operations of union and addition S+T=\makeset{m+n}{m \in S, \: n \in T} and with ultimately periodic constants is exactly the class of hyper-arithmetical sets. Equations using addition only can represent every hyper-arithmetical set under a simple encoding. All hyper-arithmetical sets can also be represented by equations over sets of natural numbers equipped with union, addition and subtraction S \dotminus T=\makeset{m-n}{m \in S, \: n \in T, \: m \geqslant n}. Testing whether a given system has a solution is $\Sigma^1_1$-complete for each model. These results, in particular, settle the expressive power of the most general types of language equations, as well as equations over subsets of free groups.Comment: 12 apges, 0 figure

Statistical Survey of Type III Radio Bursts at Long Wavelengths Observed by the Solar TErrestrial RElations Observatory (STEREO)/Waves Instruments: Radio Flux Density Variations with Frequency

We have performed a statistical study of $152$ Type III radio bursts observed by Solar TErrestrial RElations Observatory (STEREO)/Waves between May 2007 and February 2013. We have investigated the flux density between $125$kHz and $16$MHz. Both high- and low-frequency cutoffs have been observed in $60\,$ of events suggesting an important role of propagation. As already reported by previous authors, we observed that the maximum flux density occurs at $1$MHz on both spacecraft. We have developed a simplified analytical model of the flux density as a function of radial distance and compared it to the STEREO/Waves data.Comment: published in Solar Physic

The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration

Integrin β3 is seen as a key anti-angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro- or anti-angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3-dependent adhesome. We show that depletion of β3-integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3-integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2-driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3-integrin levels are reduced

Present Effects of Past Wildfires on Leaf Litter Breakdown in Stream Ecosystems

We investigated the present effects from a 10-year-old wildfire on leaf litter breakdown rates in 3 headwater streams in central Idaho. These systems experienced a massive debris flow one year after the fire. Based on soil instability and burn patterns, we identified 3 stream conditions: unburned, burned only, and burned/scoured. We placed leaf bags containing willow leaves (Salix sp.) in each stream type and removed bags at various time intervals until all bags were collected 100 days after their introduction. Leaf material was dried and weighed, and decay rate coefficients were calculated. Macroinvertebrates colonizing the bags were enumerated and identified, and selected taxa were placed into trophic groups. We found that the unburned stream had the fastest leaf litter breakdown rate, the lowest level of incident light reaching the stream, and the largest amount of benthic organic matter. The burned/scoured stream was nearly opposite in all respects. Numbers of 2 detritivore invertebrate taxa, Serratella tibialis and Zapada oregonensis, were highest in the unburned stream but lowest in the burned/scoured stream. A third taxon, Baetis sp., showed the opposite relationship. Presence of predatory invertebrates did not affect detritivore abundance or leaf decay rate in the bags. Our research suggests that recovery response variables of some stream systems may not have returned to prefire levels even a decade after the initial wildfire. In this study, the recovery of our streams appears to be connected to the return of the riparian zone, though fire-induced debris flows may slow or alter final recovery of the stream system