The Contribution of Heredity to Clinical Obesity

In order to discuss the contribution of heredity to clinical obesity, we first need to define our terms of reference to give us the common ground that is needed to explore the relationship between heredity, the environment, and clinical obesity. This will also serve to introduce these subjects for later chapters of this volume covering other aspects of the relative contributions of heredity and environment to the final clinical outcome of obesity. The importance of understanding the mechanisms underlying obesity cannot be overstated. Global rates of obesity are rising fast in most countries and the economic implications for maintaining the health care systems of those countries under the increasing burden of comorbidities and ill health are enormous [1]. Defining Heredity Heredity can simply be defined as the transmission of characteristic traits from parent to offspring. In the mid-nineteenth century, Mendel took this idea and by painstaking experimentation was able to formalize it as his two laws of heredity: the law of segregation and the law of independent assortment. The study of the science of heredity is genetics. In the twenty-first century, we now know the molecular basis of the principles of heredity and though our understanding of human genetics is by no means complete, the information that we have on DNA, the human genome sequence, epigenetics, and the environment all inform our understanding of heredity. We should be clear from the outset that using the term heredity does not imply that there is a purely genetic mechanism underlying the transmission of a trait. For many common traits, and for common obesity in particular, the influence of the environment is clearly strong

Characterisation of the impact response of energetic materials: observation of a low-level reaction in 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105)

Time-resolved and integrated diagnostics including high-speed photography, mass and optical spectroscopy, and optical-radiometry were used to study the impact response of high explosives in substantially more detail than possible with conventional sensitiveness tests. Specifically, we compare pentaerythritol tetranitrate (PETN) and cyclotetramethylene tetranitramine (HMX), with 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105), the latter of which is currently receiving a great deal of interest as a promising insensitive high explosive. We conclude that under modest impact conditions, LLM-105 can undergo a low-level reaction whose characteristics explain apparently contradictory sensitiveness results obtained using standard tests. Our results demonstrate how more sophisticated diagnostics with large dynamic ranges, can quantify the hazard response of energetic materials in detail, enabling complex behaviour to be distinguished.The authors wish to acknowledge the funding and provision of samples for this research by AWE plc.This is the author accepted manuscript. The final version is available from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C6RA03096

Adapted qPCR methodology to detect telomere oxidative damage (TOD) associated with telomere attrition (TA) in murine tissue

Numerous Studies suggest that oxidative stress (OS) is associated with telomere attrition (TA) but they rarely directly assay telomeric oxidative damage (TOD). TOD can alter shelterin binding, induce replication fork stalling and inhibit telomerase activity. We used a previously published method 1 to measure TOD and adapted it for use in murine tissue. Our model is a C57BL/6J mouse strain and we used qPCR and a formamidopyrimidine DNA glycosylase (FPG) enzyme-based qPCR method to directly determine TOD. FPG analysis compares reaction efficiencies before and after treatment. FPG is normally involved in base excision repairs pathways, removing oxidized Purines (notably 8-Oxo Guanine). A reduction in the efficiency of the qPCR indicates the presence of 8-oxo guanine in the telomeric tract ie TOD

Sensitivity to speech rhythm explains individual differences in reading ability independently of phonological awareness

This study considered whether sensitivity to speech rhythm can predict concurrent variance in reading attainment after individual differences in age, vocabulary and phonological awareness have been controlled. Five to six-year-old English-speaking children completed a battery of phonological processing assessments and reading assessments, along with a simple word stress manipulation task. The results showed that performance on the stress manipulation measure predicted a significant amount of variance in reading attainment after age, vocabulary, and phonological processing had been taken into account. These results suggest that stress sensitivity is an important, yet neglected aspect of English-speaking children?s phonological representations, which needs to be incorporated into theoretical accounts of reading development

A study of the efficacy and cost-effectiveness of MRSA screening and monitoring on surgical wards using a new, rapid molecular test (EMMS)

<p>Abstract</p> <p>Background</p> <p>MRSA is a significant contributor to prolonged hospital stay, poor clinical outcome and increased healthcare costs amongst surgical patients. A PCR test has been developed for rapid detection of MRSA in nasal swabs. The aims of this study are (1) to estimate the effectiveness of screening using this rapid PCR tests vs culture in reducing MRSA cross-infection rates; (2) to compare the cost of each testing strategy, including subsequent health care costs; and (3) to model different policies for the early identification and control of MRSA infection in surgical patients.</p> <p>Methods/Design</p> <p>The study is a prospective two-period cross-over study set in 7 surgical wards covering different surgical specialities. A total of 10,000 patients > 18 years will be tested over 16 months. The only difference between the two study periods is the method used for the detection of MRSA in each ward (rapid v conventional culture), with all other infection control practices remaining consistent between the arms. The study has been designed to complement routine practice in the NHS. Outcomes are MRSA cross-infection rates (primary outcome) and need for antibiotic therapy and MRSA-related morbidity. Parallel economic and modelling studies are being conducted to aid in the interpretation of the results and to evaluate the cost-effectiveness of the rapid PCR screening strategy.</p> <p>Discussion</p> <p>This paper highlights the design, methods and operational aspects of a study evaluating rapid MRSA screening in the surgical ward setting.</p

Choice of gDNA isolation method has a significant impact on average murine Telomere Length estimates

Telomere Length (TL) and integrity is significantly associated with age-related disease, multiple genetic and environmental factors. We observe mouse genomic DNA (gDNA) isolation methods to have a significant impact on average TL estimates. The canonical qPCR method does not measure TL directly but via the ratio of telomere repeats to a single copy gene (SCG) generating a T/S ratio. We use a monochromatic-multiplex-qPCR (mmqPCR) method which multiplexes the PCR and enables quantification of the target and the single copy gene within the same qPCR reaction. We demonstrate that TL measurements, from murine gDNA, isolated via Spin Columns (SC) and Magnetic Beads (MB), generate significantly smaller T/S ratios compared to gDNA isolated via traditional phenol/chloroform methods. The former methods may impede correct TL estimation by producing non representative fragment sets and reducing qPCR efficacy. This work highlights discrepancies in TL measurements due to different extraction techniques. We recommend the use of gDNA isolation methods that are shown to preserve DNA length and integrity, such as phenol/chloroform isolation. We propose that widely used high throughput DNA isolation methodologies can create spurious associations within a sample set, thus creating misleading data. We suggest that published TL associations should be revisited in the light of these dat

Systematic review and metaanalysis of genetic association studies of urinary symptoms and prolapse in women

Peer reviewe

Addressing the threat of climate change to agriculture requires improving crop resilience to short-term abiotic stress

Climate change represents a serious threat to global agriculture, necessitating the development of more environmentally resilient crops to safeguard the future of food production. The effects of climate change are appearing to include a higher frequency of extreme weather events and increased day-to-day weather variability. As such, crops which are able to cope with short-term environmental stress, in addition to those that are tolerant to longer term stress conditions are required . It is becoming apparent that the hitherto relatively little studied process of post-stress plant recovery could be key to optimizing growth and production under fluctuating conditions with intermittent transient stress events. Developing more durable crops requires the provision of genetic resources to identify useful traits through the development of screening protocols. Such traits can then become the objective of crop breeding programmes. In this study, we discuss these issues and outline example research in leafy vegetables that is investigating resilience to short-term abiotic stress

Association between statin use after diagnosis of esophageal cancer and survival: a population-based cohort study

Background & Aims: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors), commonly prescribed to prevent cardiovascular disease, promote apoptosis and limit proliferation of esophageal cancer cell lines. We investigated whether statin use following diagnosis of esophageal cancer is associated with reduced esophageal cancer-specific and all-cause mortality.  Methods: We identified a cohort of 4445 men and women in the United Kingdom diagnosed with esophageal cancer from January 2000 through November 2009 using the General Practice Research Database. The National Cancer Registry and Office of National Statistics datasets respectively established the histologic subtype and cancer-specific mortality. Cox proportional hazard regression analysis with time-dependent exposures estimated the association between statin use after diagnosis and esophageal cancer-specific and all-cause mortality.  Results: The median survival time of the entire cohort was 9.2 months (inter-quartile range [IQR], 3.7–23.2 months). Among subjects who used statins after diagnosis of esophageal cancer, the median survival time was 14.9 months (IQR, 7.1–52.3) compared to 8.1 months for non-users (IQR, 3.3–20). In the entire cohort, statin use after diagnosis was associated with a decreased risk of esophageal cancer-specific mortality (adjusted hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.44–0.86) and all-cause mortality (HR, 0.67; 95% CI, 0.58–0.77). In patients with esophageal adenocarcinoma, statin use after diagnosis was associated with decreased risk of esophageal cancer-specific mortality (HR, 0.61; 95% CI 0.38–0.96) and all-cause mortality (HR, 0.63; 95% 0.43–0.92). This effect was not observed in patients with esophageal squamous cell carcinoma. There was no evidence for effect modification of these associations with statin use before cancer diagnosis.  Conclusions: In a large population-based cohort, statin use after diagnosis of esophageal adenocarcinoma, but not esophageal squamous cell carcinoma, was associated with reduced esophageal cancer-specific and all-cause mortality