Circulating microRNA 122 in the methionine and choline‐deficient mouse model of non‐alcoholic steatohepatitis

Non‐alcoholic steatohepatitis (NASH) is a progressive form of non‐alcoholic fatty liver disease (NAFLD) and is a major cause of liver cirrhosis and hepatic failure. The methionine choline‐deficient diet (MCD) is a frequently used hepatotoxicity animal model of NASH that induces hepatic transaminase (ALT, AST) elevations and hepatobiliary histological changes similar to those observed in human NASH. Liver‐specific microRNA‐122 (miR‐122) has been shown as a key regulator of cholesterol and fatty acid metabolism in adult liver, and has recently been proposed as a sensitive and specific circulating biomarker of hepatic injury. The purpose of this study was to assess miR‐122 serum levels in mice receiving an MCD diet for 0, 3, 7, 14, 28 and 56 days and compare the performance vs. routine clinical chemistry when benchmarked against the histopathological liver findings. MiR‐122 levels were quantified in serum using RT‐qPCR. Both miR‐122 and ALT/AST levels were significantly elevated in serum at all timepoints. MiR‐122 levels increased on average by 40‐fold after 3 days of initiating the MCD diet, whereas ALT and AST changes were 4.8‐ and 3.3‐fold, respectively. In general, miR‐122 levels remained elevated across all time points, whereas the ALT/AST increases were less robust but correlated with the progressive severity of NASH as assessed by histopathology. In conclusion, serum levels of miR‐122 can potentially be used as a sensitive biomarker for the early detection of hepatotoxicity and can aid in monitoring the extent of NAFLD‐associated liver injury in mouse efficacy models. Copyright © 2013 John Wiley & Sons, Ltd.     

Quality of breast cancer sites on the World Wide Web

The Internet is a powerful tool for accessing information about complex health topics. The purpose of this study was to evaluate breast cancer Internet sites using published criteria about website structure. Two searches were undertaken (November 1998 and June 1999) using the Yahoo search engine, providing a sample of 136 unique addresses. The results showed 1) owner's credentials were identified in 31.6% of sites, 2) financial charges were stated in 10.3% of sites, 3) less than 14.0% identified site creation date, 4) 33.1% identified content posting update, 5) 30.1% identified information sources, and 6) just under 88% of sites provided e-mail interactivity. The results indicate variability in breast cancer Internet sites with respect to framework criteria of accountability. We suggest that websites that lack fundamental indicators (such as dating and sources) do not provide the user with fundamental information that could enable informed decision making about site quality.     

Dietary Advanced Glycation End Products and Risk Factors for Chronic Disease: A Systematic Review of Randomised Controlled Trials

Dietary advanced glycation end-products (AGEs) form during heating and processing of food products and are widely prevalent in the modern Western diet. Recent systematic reviews indicate that consumption of dietary AGEs may promote inflammation, oxidative stress and insulin resistance. Experimental evidence indicates that dietary AGEs may also induce renal damage, however, this outcome has not been considered in previous systematic reviews. The purpose of this review was to examine the effect of consumption of a high AGE diet on biomarkers of chronic disease, including chronic kidney disease (CKD), in human randomized controlled trials (RCTs). Six databases (SCOPUS, CINHAL, EMBASE, Medline, Biological abstracts and Web of Science) were searched for randomised controlled dietary trials that compared high AGE intake to low AGE intake in adults with and without obesity, diabetes or CKD. Twelve dietary AGE interventions were identified with a total of 293 participants. A high AGE diet increased circulating tumour necrosis factor-alpha and AGEs in all populations. A high AGE diet increased 8-isoprostanes in healthy adults, and vascular cell adhesion molecule-1 (VCAM-1) in patients with diabetes. Markers of CKD were not widely assessed. The evidence presented indicates that a high AGE diet may contribute to risk factors associated with chronic disease, such as inflammation and oxidative stress, however, due to a lack of high quality randomised trials, more research is required.     

Detection of 12.5% and 25% Salt Reduction in Bread in a Remote Indigenous Australian Community

Food reformulation is an important strategy to reduce the excess salt intake observed in remote Indigenous Australia. We aimed to examine whether 12.5% and 25% salt reduction in bread is detectable, and, if so, whether acceptability is changed, in a sample of adults living in a remote Indigenous community in the Northern Territory of Australia. Convenience samples were recruited for testing of reduced-salt (300 and 350 mg Na/100 g) versus Standard (~400 mg Na/100 g) white and wholemeal breads (n = 62 for white; n = 72 for wholemeal). Triangle testing was used to examine whether participants could detect a difference between the breads. Liking of each bread was also measured; standard consumer acceptability questionnaires were modified to maximise cultural appropriateness and understanding. Participants were unable to detect a difference between Standard and reduced-salt breads (all p values > 0.05 when analysed using binomial probability). Further, as expected, liking of the breads was not changed with salt reduction (all p values > 0.05 when analysed using ANOVA). Reducing salt in products commonly purchased in remote Indigenous communities has potential as an equitable, cost-effective and sustainable strategy to reduce population salt intake and reduce risk of chronic disease, without the barriers associated with strategies that require individual behaviour change.     

Calcium absorption and kinetics are similar in 7- and 8-year-old Mexican-American and Caucasian girls despite hormonal differences

To assess the possibility of ethnic differences in mineral metabolism in prepubertal children, we compared measures of calcium metabolism in 7- and 8-y-old Mexican-American (MA) and non-Hispanic Caucasian (CAU) girls (n = 38) living in southeastern Texas. We found similar fractional calcium absorption, urinary calcium excretion, calcium kinetic values and total-body bone mineral content in the MA and CAU girls. In contrast, parathyroid hormone (PTH) concentrations were greater in MA girls (4.01 +/- 0.47 vs. 1. 96 +/- 0.50 pmol/L, P = 0.005) than in CAU girls. Serum 25-hydroxyvitamin D concentrations were lower in MA girls (68.9 +/- 7.7 vs. 109.4 +/- 8.4 nmol/L, P = 0.001) than in CAU girls, but 1, 25-dihydroxyvitamin D concentrations did not differ between groups. Seasonal variability was seen for 25-hydroxyvitamin D concentrations in girls of both ethnic groups, but values in all of the girls were >30 nmol/L (12 ng/mL). We conclude the following: 1) greater PTH levels in MA girls than CAU girls are present without evidence of vitamin D deficiency; and 2) differences in 25-hydroxyvitamin D and PTH concentrations between MA and CAU girls do not have a large effect on calcium absorption, excretion or bone calcium kinetics. These data do not provide evidence for adjusting dietary recommendations for mineral or vitamin D intake by MA girls.     

Micronutrients: highlights and research challenges from the 1994-5 National Diet and Nutrition Survey of people aged 65 years and over

The aims of the National Diet and Nutrition Survey series are summarized, and the new National Diet and Nutrition Survey of people aged 65 years and over is explored, with particular emphasis on micronutrient intakes and status indices. Mean nutrient intakes were generally satisfactory for most micronutrients, but intakes of vitamin D, Mg, K and Cu were low. Intakes of vitamin D were far below the reference nutrient intake for people aged 65 years and over, and there was also biochemical evidence of vitamin D deficiency, for 8% of free-living and 37% of institution participants, attributed partly to limited exposure to sunlight. A substantial proportion of people living in institutions had inadequate biochemical status indices, notably for vitamin C, Fe and folate. Relationships between intake and status were close for vitamins. Mineral intakes did not correlate well with currently used status indices. Some intakes and indices, especially those of vitamin C, carotenoids, Na and K, were strongly correlated with socio-economic status and with north-south gradients in Britain. Future research challenges should address the functional and health significance of low intakes and sub-optimal biochemical indices for certain micronutrients, especially for people living in institutions; the shortcomings of mineral status indices especially as indicators of mineral intake; the social and geographical inequalities of micronutrient intakes and status, and why micronutrient status deteriorates with increasing age. The answers to these questions will help to define the characteristics of nutritional risk for older people in Britain, and to clarify future needs for education and intervention.     

Spontaneous abortion in the British semiconductor industry: An HSE investigation. Health and Safety Executive.

BACKGROUND: The UK Health and Safety Executive (HSE) conducted a study to examine the risk of spontaneous abortion (SAB) in British female semiconductor industry workers, following reports from the USA which suggested an association between risk of SAB and work in fabrication rooms and/or exposure to ethylene glycol ethers. METHODS: A nested case-control study based on 2,207 women who had worked at eight manufacturing sites during a 5-year retrospective time frame was established; 36 cases were matched with 80 controls. RESULTS: The overall SAB rate in the industry was 10.0%. (65 SABs/651 pregnancies) The crude odds ratio (OR) for fabrication work was 0.65 (95% CI 0.30-1.40). This was essentially unchanged after adjustment for a range of potential confounding factors in the first 3 months of pregnancy and was reduced to 0.58 (95% CI 0.26-1.30) after adjustment for smoking in the previous 12 months. There were no statistically significantly elevated ORs for any work group or any specific chemical or physical exposure in the industry. CONCLUSIONS: There is no evidence of an increased risk of SAB in the British semiconductor industry. Am. J. Ind. Med. 36:557-572, 1999. Published 1999 Wiley-Liss, Inc.     

SB-616234-A (1-[6-(cis-3,5-dimethylpiperazin-1-yl)-2,3-dihydro-5-methoxyindol-1-yl]-1-[2'methyl-4'-(5-methyl-1,2,3-oxadiazol-3-yl)biphenyl-4-yl]methanone hydrochloride): a novel, potent and selective 5-HT1B receptor antagonist

SB-616234-A possesses high affinity for human 5-HT_1B receptors stably expressed in Chinese hamster ovary (CHO) cells (pK_i 8.3 ± 0.2), and is over 100-fold selective for a range of molecular targets except h5-HT_1D receptors (pK_i 6.6 ± 0.1). Similarly, affinity (pK_i) for rat and guinea pig striatal 5-HT_1B receptors is 9.2 ± 0.1. In [³⁵S]-GTPγS binding studies in the human recombinant cell line, SB-616234-A acted as a high affinity antagonist with a pA₂ value of 8.6 ± 0.2 whilst providing no evidence of agonist activity in this system. In [³⁵S]-GTPγS binding studies in rat striatal membranes, SB-616234-A acted as a high affinity antagonist with an apparent pK_B of 8.4 ± 0.5, again whilst providing no evidence of agonist activity in this system. SB-616234-A (1 μM) potentiated electrically stimulated [³H]-5-HT release from guinea pig and rat cortical slices (S₂/S₁ ratios of 1.8 and 1.6, respectively). SB-616234-A (0.3–30 mg kg⁻¹ p.o.) caused a dose-dependent inhibition of ex vivo [³H]-GR125743 binding to rat striatal 5-HT_1B receptors with an ED₅₀ of 2.83 ± 0.39 mg kg⁻¹ p.o. Taken together these data suggest that SB-616234-A is a potent and selective 5-HT_1B autoreceptor antagonist that occupies central 5-HT_1B receptors in vivo following oral administration.     

The radicalized self: the impact on the self of the contested nature of the diagnosis of chronic fatigue syndrome

Chronic fatigue syndrome (CFS) is a relatively new disease that is difficult to diagnose. It is also a contested disease immersed in dispute about whether it is a physical or psychiatric reality. Sufferers often claim to experience not only the physical challenges of the disease, and these can be extensive, but also, initially, the anomie of suffering from a condition whose very reality is debated both in the medical and in the wider communities. Theories of self in illness emphasize how people who are diagnosed as chronically ill work hard as they seek to maintain previous, or to develop supernormal, selves. Such goals are cast in a critical light by Foucault's notion of the technologies of self in the context of circulating neo-liberal discourses. As people with CFS, lacking an uncontested medical diagnosis, search for meaningful self-identities, they resist previously available discourses to take up an alternative discourse, one that we call radicalized selves. This paper raises questions about the constraints and liberties, power and powerlessness associated with a clear and undisputed medical diagnosis. It suggests a model of the self in chronic illness that considers not only changes in body and biography but also the availability of an uncontested diagnosis.