Adiposity has differing associations with incident coronary heart disease and mortality in the Scottish population: cross-sectional surveys with follow-up

Objective: Investigation of the association of excess adiposity with three different outcomes: all-cause mortality, coronary heart disease (CHD) mortality and incident CHD. Design: Cross-sectional surveys linked to hospital admissions and death records. Subjects: 19 329 adults (aged 18–86 years) from a representative sample of the Scottish population. Measurements: Gender-stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality, CHD mortality and incident CHD. Separate models incorporating the anthropometric measurements body mass index (BMI), waist circumference (WC) or waist–hip ratio (WHR) were created adjusted for age, year of survey, smoking status and alcohol consumption. Results: For both genders, BMI-defined obesity (greater than or equal to30 kg m−2) was not associated with either an increased risk of all-cause mortality or CHD mortality. However, there was an increased risk of incident CHD among the obese men (hazard ratio (HR)=1.78; 95% confidence interval=1.37–2.31) and obese women (HR=1.93; 95% confidence interval=1.44–2.59). There was a similar pattern for WC with regard to the three outcomes; for incident CHD, the HR=1.70 (1.35–2.14) for men and 1.71 (1.28–2.29) for women in the highest WC category (men greater than or equal to102 cm, women greater than or equal to88 cm), synonymous with abdominal obesity. For men, the highest category of WHR (greater than or equal to1.0) was associated with an increased risk of all-cause mortality (1.29; 1.04–1.60) and incident CHD (1.55; 1.19–2.01). Among women with a high WHR (greater than or equal to0.85) there was an increased risk of all outcomes: all-cause mortality (1.56; 1.26–1.94), CHD mortality (2.49; 1.36–4.56) and incident CHD (1.76; 1.31–2.38). Conclusions: In this study excess adiposity was associated with an increased risk of incident CHD but not necessarily death. One possibility is that modern medical intervention has contributed to improved survival of first CHD events. The future health burden of increased obesity levels may manifest as an increase in the prevalence of individuals living with CHD and its consequences

Slepton Discovery in Electroweak Cascade Decay

The LHC studies on the MSSM slepton sector have mostly been focused on direct slepton Drell-Yan pair production. In this paper, we analyze the case when the sleptons are lighter than heavy neutralinos and can appear in the on-shell decay of neutralino states. In particular, we have studied the \chi_1^\pm \chi_2^0 associated production, with the consequent decays of \chi_1^\pm and \chi_2^0 via on-shell sleptons. The invariant mass of the lepton pairs, m_{\ell\ell}, from the neutralino decay has a distinctive triangle shape with a sharp kinematic cutoff. We discuss the utilization of this triangle shape in m_{\ell\ell} distribution to identify the slepton signal. We studied the trilepton plus missing E_T signal and obtained the effective cross section, \sigma \times BR \times acceptance, that is needed for a 5\sigma discovery as a function of the cutoff mass for the LHC with center of mass energy 14 TeV and 100 fb^{-1} integrated luminosity. Our results are model independent such that they could be applied to other models with similar decay topology. When applied to the MSSM under simple assumptions, it is found that with 100 fb^{-1} integrated luminosity, a discovery reach in the left-handed slepton mass of about 600 GeV could be reached, which extends far beyond the slepton mass reach in the usual Drell-Yan studies.Comment: 20 pages, 5 figure

Physiogenomic comparison of human fat loss in response to diets restrictive of carbohydrate or fat

<p>Abstract</p> <p>Background</p> <p>Genetic factors that predict responses to diet may ultimately be used to individualize dietary recommendations. We used physiogenomics to explore associations among polymorphisms in candidate genes and changes in relative body fat (Δ%BF) to low fat and low carbohydrate diets.</p> <p>Methods</p> <p>We assessed Δ%BF using dual energy X-ray absorptiometry (DXA) in 93 healthy adults who consumed a low carbohydrate diet (carbohydrate ~12% total energy) (LC diet) and in 70, a low fat diet (fat ~25% total energy) (LF diet). Fifty-three single nucleotide polymorphisms (SNPs) selected from 28 candidate genes involved in food intake, energy homeostasis, and adipocyte regulation were ranked according to probability of association with the change in %BF using multiple linear regression.</p> <p>Results</p> <p>Dieting reduced %BF by 3.0 ± 2.6% (absolute units) for LC and 1.9 ± 1.6% for LF (p < 0.01). SNPs in nine genes were significantly associated with Δ%BF, with four significant after correction for multiple statistical testing: rs322695 near the retinoic acid receptor beta (<it>RARB</it>) (p < 0.005), rs2838549 in the hepatic phosphofructokinase (<it>PFKL</it>), and rs3100722 in the histamine N-methyl transferase (<it>HNMT</it>) genes (both p < 0.041) due to LF; and the rs5950584 SNP in the angiotensin receptor Type II (<it>AGTR2</it>) gene due to LC (p < 0.021).</p> <p>Conclusion</p> <p>Fat loss under LC and LF diet regimes appears to have distinct mechanisms, with <it>PFKL </it>and <it>HNMT </it>and <it>RARB </it>involved in fat restriction; and <it>AGTR2 </it>involved in carbohydrate restriction. These discoveries could provide clues to important physiologic mechanisms underlying the Δ%BF to low carbohydrate and low fat diets.</p

Transoral laser microsurgery for laryngeal cancer: A primer and review of laser dosimetry

Transoral laser microsurgery (TLM) is an emerging technique for the management of laryngeal and other head and neck malignancies. It is increasingly being used in place of traditional open surgery because of lower morbidity and improved organ preservation. Since the surgery is performed from the inside working outward as opposed to working from the outside in, there is less damage to the supporting structures that lie external to the tumor. Coupling the laser to a micromanipulator and a microscope allows precise tissue cutting and hemostasis; thereby improving visualization and precise ablation. The basic approach and principles of performing TLM, the devices currently in use, and the associated dosimetry parameters will be discussed. The benefits of using TLM over conventional surgery, common complications and the different settings used depending on the location of the tumor will also be discussed. Although the CO2 laser is the most versatile and the best-suited laser for TLM applications, a variety of lasers and different parameters are used in the treatment of laryngeal cancer. Improved instrumentation has lead to an increased utilization of TLM by head and neck cancer surgeons and has resulted in improved outcomes. Laser energy levels and spot size are adjusted to vary the precision of cutting and amount of hemostasis obtained

Ketamine Influences CLOCK:BMAL1 Function Leading to Altered Circadian Gene Expression

Major mood disorders have been linked to abnormalities in circadian rhythms, leading to disturbances in sleep, mood, temperature, and hormonal levels. We provide evidence that ketamine, a drug with rapid antidepressant effects, influences the function of the circadian molecular machinery. Ketamine modulates CLOCK:BMAL1-mediated transcriptional activation when these regulators are ectopically expressed in NG108-15 neuronal cells. Inhibition occurs in a dose-dependent manner and is attenuated after treatment with the GSK3β antagonist SB21673. We analyzed the effect of ketamine on circadian gene expression and observed a dose-dependent reduction in the amplitude of circadian transcription of the Bmal1, Per2, and Cry1 genes. Finally, chromatin-immunoprecipitation analyses revealed that ketamine altered the recruitment of the CLOCK:BMAL1 complex on circadian promoters in a time-dependent manner. Our results reveal a yet unsuspected molecular mode of action of ketamine and thereby may suggest possible pharmacological antidepressant strategies