Aliment Pharmacol Ther 2011; 33: 525–540
Summary
Background Non‐alcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease in Western countries. The development of ...non‐alcoholic steatohepatitis (NASH) and fibrosis identifies an at‐risk group with increased risk of cardiovascular and liver‐related deaths. The identification and management of this at‐risk group remains a clinical challenge.
Aim To perform a systematic review of the established and emerging strategies for the diagnosis and staging of NAFLD.
Methods Relevant research and review articles were identified by searching PubMed, MEDLINE and EMBASE.
Results There has been a substantial development of non‐invasive risk scores, biomarker panels and radiological modalities to identify at‐risk patients with NAFLD without recourse to liver biopsy on a routine basis. These modalities and algorithms have improved significantly in their diagnosis and staging of fibrosis and NASH in patients with NAFLD, and will likely impact on the number of patients undergoing liver biopsy.
Conclusions Staging for NAFLD can now be performed by a combination of radiological and laboratory techniques, greatly reducing the requirement for invasive liver biopsy.
A method for nucleic-acid-based detection of pathogens in plant material has been developed which comprises a simple and rapid method for extracting DNA on the nitrocellulose membranes of ...lateral-flow devices, loop-mediated isothermal amplification (LAMP) of target DNA using labeled primers, and detection of the generically labeled amplification products by a sandwich immunoassay in a lateral-flow-device format. Each of these steps can be performed without specialist equipment and is suitable for on-site use, and a result can be obtained in just over an hour. A LAMP assay for the detection of plant DNA (cytochrome oxidase gene) can be used in conjunction with pathogen-specific assays to confirm negative results. The use of this method is demonstrated for the detection of Phytophthora ramorum, the causal agent of sudden oak death and dieback/leaf blight in a range of tree, shrub, and herbaceous species, and the recently described pathogen P. kernoviae.
Mineral dust aerosols often observed over California in winter and spring, associated with long-range transport from Asia and the Sahara, have been linked to enhanced precipitation based on ...observations. Local anthropogenic pollution, on the other hand, was shown in previous observational and modeling studies to reduce precipitation. Here we incorporate recent developments in ice nucleation parameterizations to link aerosols with ice crystal formation in a spectral-bin cloud microphysical model coupled with the Weather Research and Forecasting (WRF) model in order to examine the relative and combined impacts of dust and local pollution particles on cloud properties and precipitation type and intensity. Simulations are carried out for two cloud cases (from the CalWater 2011 field campaign) with contrasting meteorology and cloud dynamics that occurred on 16 February (FEB16) and 2 March (MAR02). In both cases, observations show the presence of dust and biological particles in a relative pristine environment. The simulated cloud microphysical properties and precipitation show reasonable agreement with aircraft and surface measurements. Model sensitivity experiments indicate that in the pristine environment, the dust and biological aerosol layers increase the accumulated precipitation by 10-20% from the Central Valley to the Sierra Nevada for both FEB16 and MAR02 due to a ~40% increase in snow formation, validating the observational hypothesis. Model results show that local pollution increases precipitation over the windward slope of the mountains by a few percent due to increased snow formation when dust is present, but reduces precipitation by 5-8% if dust is removed on FEB16. The effects of local pollution on cloud microphysics and precipitation strongly depend on meteorology, including cloud dynamics and the strength of the Sierra Barrier Jet. This study further underscores the importance of the interactions between local pollution, dust, and environmental conditions for assessing aerosol effects on cold-season precipitation in California.
Obesity is associated with functional limitations in muscle performance and increased likelihood of developing a functional disability such as mobility, strength, postural and dynamic balance ...limitations. The consensus is that obese individuals, regardless of age, have a greater absolute maximum muscle strength compared to non-obese persons, suggesting that increased adiposity acts as a chronic overload stimulus on the antigravity muscles (e.g., quadriceps and calf), thus increasing muscle size and strength. However, when maximum muscular strength is normalised to body mass, obese individuals appear weaker. This relative weakness may be caused by reduced mobility, neural adaptations and changes in muscle morphology. Discrepancies in the literature remain for maximal strength normalised to muscle mass (muscle quality) and can potentially be explained through accounting for the measurement protocol contributing to muscle strength capacity that need to be explored in more depth such as antagonist muscle co-activation, muscle architecture, a criterion valid measurement of muscle size and an accurate measurement of physical activity levels. Current evidence demonstrating the effect of obesity on muscle quality is limited. These factors not being recorded in some of the existing literature suggest a potential underestimation of muscle force either in terms of absolute force production or relative to muscle mass; thus the true effect of obesity upon skeletal muscle size, structure and function, including any interactions with ageing effects, remains to be elucidated.
Heatwaves present a significant health risk and the hazard is likely to escalate with the increased future temperatures presently predicted by climate change models. The impact of heatwaves is often ...felt strongest in towns and cities where populations are concentrated and where the climate is often unintentionally modified to produce an urban heat island effect; where urban areas can be significantly warmer than surrounding rural areas. The purpose of this interdisciplinary study is to integrate remotely sensed urban heat island data alongside commercial social segmentation data via a spatial risk assessment methodology in order to highlight potential heat health risk areas and build the foundations for a climate change risk assessment. This paper uses the city of Birmingham, UK as a case study area.
When looking at vulnerable sections of the population, the analysis identifies a concentration of "very high" risk areas within the city centre, and a number of pockets of "high risk" areas scattered throughout the conurbation. Further analysis looks at household level data which yields a complicated picture with a considerable range of vulnerabilities at a neighbourhood scale.
The results illustrate that a concentration of "very high" risk people live within the urban heat island, and this should be taken into account by urban planners and city centre environmental managers when considering climate change adaptation strategies or heatwave alert schemes. The methodology has been designed to be transparent and to make use of powerful and readily available datasets so that it can be easily replicated in other urban areas.
Phytophthora ramorum is the causal agent of sudden oak death. The pathogen also affects a wide range of tree, shrub, and herbaceous species in natural and landscaped environments as well as plants in ...the nursery industry. A TaqMan real-time PCR method for the detection of this pathogen in the field has been described previously; this paper describes the development of a number of assays based on this method which have various advantages for use in the field. A scorpion real-time PCR assay that is twice as fast as TaqMan was developed, allowing the detection of P. ramorum in less than 30 min. Also designed was a loop-mediated isothermal amplification (LAMP) assay, which allowed sensitive and specific detection of P. ramorum in 45 min using only a heated block. A positive reaction was identified by the detection of the LAMP product by color change visible to the naked eye.
Summary
Background
Non‐alcoholic fatty liver disease has reached epidemic proportions in type 2 diabetes (T2D). Glucagon‐like peptide‐1 analogues are licensed in T2D, yet little data exist on ...efficacy and safety in liver injury.
Aim
To assess the safety and efficacy of 26‐week liraglutide on liver parameters in comparison with active‐placebo.
Methods
Individual patient data meta‐analysis was performed using patient‐level data combined from six 26‐week, phase‐III, randomised controlled T2D trials, which comprise the ‘Liraglutide Effect and Action in Diabetes’ (LEAD) program. The LEAD‐2 sub‐study was analysed to assess the effect on CT‐measured hepatic steatosis.
Results
Of 4442 patients analysed, 2241 (50.8%) patients had an abnormal ALT at baseline mean ALT 33.8(14.9) IU/L in females; 47.3(18.3) IU/L in males. Liraglutide 1.8 mg reduced ALT in these patients vs. placebo (−8.20 vs. −5.01 IU/L; P = 0.003), and was dose‐dependent (no significant differences vs. placebo with liraglutide 0.6 or 1.2 mg). This effect was lost after adjusting for liraglutide's reduction in weight (mean ALT difference vs. placebo −1.41 IU/L, P = 0.21) and HbA1c (+0.57 IU/L, P = 0.63). Adverse effects with 1.8 mg liraglutide were similar between patients with and without baseline abnormal ALT. In LEAD‐2 sub‐study, liraglutide 1.8 mg showed a trend towards improving hepatic steatosis vs. placebo (liver‐to‐spleen attenuation ratio +0.10 vs. 0.00; P = 0.07). This difference was reduced when correcting for changes in weight (+0.06, P = 0.25) and HbA1c (0.00, P = 0.93).
Conclusions
Twenty‐six weeks' liraglutide 1.8 mg is safe, well tolerated and improves liver enzymes in patients with type 2 diabetes. This effect appears to be mediated by its action on weight loss and glycaemic control.
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