Investigation of glycaemic traits in psychiatric disorders using Mendelian randomisation revealed a causal relationship with anorexia nervosa

Data from observational studies have suggested an involvement of abnormal glycaemic regulation in the pathophysiology of psychiatric illness. This may be an attractive target for clinical intervention as glycaemia can be modulated by both lifestyle factors and pharmacological agents. However, observational studies are inherently confounded, and therefore, causal relationships cannot be reliably established. We employed genetic variants rigorously associated with three glycaemic traits (fasting glucose, fasting insulin, and glycated haemoglobin) as instrumental variables in a two-sample Mendelian randomisation analysis to investigate the causal effect of these measures on the risk for eight psychiatric disorders. A significant protective effect of a natural log transformed pmol/L increase in fasting insulin levels was observed for anorexia nervosa after the application of multiple testing correction (OR = 0.48 [95% CI: 0.33-0.71]—inverse-variance weighted estimate). There was no consistently strong evidence for a causal effect of glycaemic factors on the other seven psychiatric disorders considered. The relationship between fasting insulin and anorexia nervosa was supported by a suite of sensitivity analyses, with no statistical evidence of instrument heterogeneity or horizontal pleiotropy. Further investigation is required to explore the relationship between insulin levels and anorexia.Subject terms: Genetics, Risk factors, Psychiatric disorders     

Body mass index centile charts to assess fatness of British children.

Body mass index (BMI) relates weight to height and reflects the shape of a child, but because of age dependency it has not been used conventionally for the estimation of fatness in children. From measurements of Tayside children (n = 34,533) centile charts were constructed for BMI (wt/ht2) from the raw data of height and weight, using Cole''s LMS method for normalised growth standards. These data were compared with the only available European BMI charts published from data of French children obtained over a period of 24 years from 1956-79. British children appear to be ''fatter''. Within a subgroup (n = 445) the BMI values were correlated with estimations of body fat, for boys and girls, from skinfold thickness (r = 0.8 and 0.81) and bioelectrical impedance (r = 0.65 and 0.7). The limits of acceptable BMI have yet to be defined.     

The effects of lidocaine and adrenergic agonists on rat sciatic nerve and skeletal muscle blood flow in vivo

It has been proposed that epinephrine prolongs lidocaine nerve blockade duration by exerting a local vasoconstrictive effect on tissues at the injection site, slowing lidocaine's local clearance. However, previous studies have failed to demonstrate consistent effects of lidocaine and epinephrine, injected alone and in combination, on vascular tone or regional blood flow. To reinvestigate this idea, in this study we used the radiolabeled microsphere technique to measure in vivo tissue blood flow before and at several time points after perisciatic nerve and intramasseter muscle injection of lidocaine alone, epinephrine, the selective alpha(1)-adrenergic receptor agonist phenylephrine, or lidocaine combined with these adrenergic receptor agonists. Repeated-measures analyses of variance were used to assess significant changes in blood flow over time. Lidocaine (2, 10, and 20 mg/mL) and epinephrine (10 micro g/mL or 1:100,000) injected alone did not alter blood flow in sciatic nerve, perisciatic muscle, or masseter muscle. Injections of lidocaine (10 mg/mL) combined with epinephrine (10 micro g/mL) did not affect adjacent muscle blood flow but caused a mild reduction in sciatic nerve blood flow, which was significant 30 min after injection. However, phenylephrine (10 micro g/mL), a potent vasoconstrictor, combined with lidocaine (10 mg/mL) significantly reduced blood flow in all three tissues. Our findings suggest that mechanisms other than local vasoconstriction may contribute to the prolongation of lidocaine nerve blocks by epinephrine. IMPLICATIONS: Accepting that the microsphere technique may be limited in its sensitivity to detect small but clinically relevant changes in tissue blood flow, our findings suggest that mechanisms other than local vasoconstriction may contribute to the prolongation of lidocaine nerve blocks by epinephrine.     

Laminar distribution of the pathological changes in the cerebral cortex in variant Creutzfeldt-Jakob disease (vCJD)

To determine the pattern of cortical degeneration in cases of variant Creutzfeldt-Jakob disease (vCJD), the laminar distribution of the vacuolation ("spongiform change"), surviving neurones, glial cell nuclei, and prion protein (PrP) deposits was studied in the frontal, parietal and temporal lobes. The vacuolation exhibited two common patterns of distribution: either the vacuoles were present throughout the cortex or a bimodal distribution was present with peaks of density in the upper and lower cortical laminae. The distribution of the surviving neurones was highly variable in different regions; the commonest pattern being a uniform distribution with cortical depth. Glial cell nuclei were distributed largely in the lower cortical laminae. The non-florid PrP deposits exhibited either a bimodal distribution or exhibited a peak of density in the upper cortex while the florid deposits were either uniformly distributed down the cortex or were present in the upper cortical laminae. In a significant proportion of areas, the density of the vacuoles was positively correlated with either the surviving neurones or with the glial cell nuclei. These results suggest similarities and differences in the laminar distributions of the pathogenic changes in vCJD compared with cases of sporadic CJD (sCJD). The laminar distribution of vacuoles was more extensive in vCJD than in sCJD whereas the distribution of the glial cell nuclei was similar in the two disorders. In addition, PrP deposits in sCJD were localised mainly in the lower cortical laminae while in vCJD, PrP deposits were either present in all laminae or restricted to the upper cortical laminae. These patterns of laminar distribution suggest that the process of cortical degeneration may be distinctly different in vCJD compared with sCJD.     

Predictors of overweight and obesity in five to seven-year-old children in Germany: Results from cross-sectional studies

Background  

Childhood obesity is a serious public health problem and epidemiological studies are important to identify predictive factors. It is the aim of this study to analyse factors associated with overweight/obesity in samples of German children.