A bivariate genome-wide approach to metabolic syndrome: STAMPEED consortium

OBJECTIVE The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ～2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from ～9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure. CONCLUSIONS Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants.     

Determinants for preventive oral health care need among community‐dwelling older people: a population‐based study

The aim was to study the determinants of preventive oral health care need among community‐dwelling old people. The study population consisted of 165 participants, a subpopulation in the Geriatric Multidisciplinary Strategy for Good Care of Elderly People (GeMS) study. Fifty‐five percent of the edentate participants with full dentures and 82% of the dentate had a need for preventive oral health care. In the total study population, the need for preventive care was associated with co‐morbidity (measured by means of the Modified Functional Co‐morbidity Index) odds ratios (OR) 1.2 (confidence intervals [CI] 1.0–1.5), being pre‐frail or frail, OR 2.5 (CI 1.2–5.1), presence of natural teeth, OR 4.8 (CI 2.2–10.4), and among dentate participants, the use of a removable partial denture, OR 12.8 (CI 1.4–114.4). Primary care clinicians should be aware of the high need for preventive care and the importance of nonoral conditions as determinants of preventive oral health care need.     

Central hypotensive effects of imidazole acetic acid and rolipram (ZK 62 711) in rats

In urethane-anaesthetized rats the administration of imidazole acetic acid (IAA), 34–272 g per rat intracerebroventricularly (i.c.v.), induced a dose-related fall in blood pressure. Rolipram (ZK 62 711), a potent and selective inhibitor of cyclic AMP phosphodiesterase (cAMP-PDE), also lowered the blood pressure in a dose-dependent manner when administered at the doses of 1–64 g per rat i.c.v. A subhypotensive dose of rolipram (0.25 g per rat i.c.v.) did not change the hypotensive effect of IAA. Pretreatment of the rats with metiamide, 1.1. mg per rat i.c.v., shifted the dose-response curve for IAA significantly to the right. The present results make it unlikely that the central hypotensive effect of IAA could be due to the stimulation of cAMP-PDE by this agent. Central histamine H₂-receptors may be involved in the hypotensive effect of IAA.     

Power spectral analysis of heart rate variability during hyperinsulinemia in nondiabetic offspring of type 2 diabetic patients: evidence for possible early autonomic dysfunction in insulin-resistant subjects.

Sympathetic activation has been considered as a link between insulin resistance, hyperinsulinemia, and hypertension. However, little is known about the association between insulin sensitivity and autonomic regulation or about the effect of acute hyperinsulinemia on cardiac sympathovagal balance. The aim of this study was to investigate heart rate variability (HRV) during the euglycemic-hyperinsulinemic clamp in nondiabetic offspring of patients with type 2 diabetes. We studied 35 nondiabetic offspring of patients with type 2 diabetes and 19 control subjects. Probands were chosen from a 10-year follow-up study of patients with well-characterized type 2 diabetes according to their fasting C-peptide level (selected from both ends of the distribution) and from control subjects to form three groups: 1) a group including subjects who were offspring of type 2 diabetic patients with low C-peptide levels (deficient insulin secretion group [IS group], n = 17), 2) a group including subjects who were offspring of type 2 diabetic patients with high C-peptide levels (insulin-resistant group [IR group], n = 18), and 3) a control group without a history of type 2 diabetes in first-degree relatives (n = 19). HRV was assessed at baseline and at the steady state during the euglycemic-hyperinsulinemic clamp. Rates of whole-body glucose uptake (M value) were lower in the IR group than in the IS group and the control group (41+/-3 vs. 54+/-2 vs. 60+/-4 micromol x kg(-1) x min(-1), P < 0.01 and P < 0.01, respectively). In all groups, heart rate increased significantly during hyperinsulinemia. In the IR group, insulin infusion increased total power of HRV [from 7.70+/-0.15 to 8.05+/-0.15 ln(ms2), P < 0.01] and the low frequency-to-high frequency ratio (from 0.62+/-0.14 to 1.14+/-0.18, P < 0.01) and decreased power of the high frequency spectral component (from 5.73+/-0.17 to 5.43+/-0.16 ln(ms2), P < 0.05), whereas in other groups, changes in HRV were not significant. We conclude that the HRV response to acute hyperinsulinemia in the offspring of type 2 diabetic probands was likely to be modulated by the type 2 diabetic phenotype of the parent. In insulin-resistant subjects, autonomic dysfunction may be an earlier defect than hitherto acknowledged.     

Systemic and regional effects of experimental gradual splanchnic ischemia

We evaluated the effects of gradual intestinal ischemia on systemic and regional haemodynamics and oxygen transport. Superior mesenteric artery (SMA) blood flow was decreased by 40%, 70%, and 100% for 60-minute periods and thereafter released in 12 pigs. Hemodynamic changes were monitored continuously, and the intestinal perfusion was evaluated by changes in portal vein-arterial lactate gradient, intramucosal pH, tonometric Pco₂, tonometric-portal vein Pco₂ gradient, and regional oxygen extraction. Local signs of intestinal hypoperfusion developed during the SMA occlusion. Intramucosal pH and portal vein pH decreased from 7.18 ± 0.04 to 6.81 ± 0.04 (P < .01) and from 7.36 ± 0.01 to 7.25 ± 0.03 (P < .05), respectively. Intramucosal Pco2 and tonometric-portal vein Pco2 gradient increased from 12.4 ± 1.3 to 21.2 ± 1.8 kPa (P < .01) and from 6.0 ± 1.3 to 14.0 ± 1.9 kPa (P < .05), respectively. Portal vein-arterial lactate gradient and splanchnic oxygen extraction increased from 0.02 ± 0.07 to 2.32 ± 0.47 mmol/L (P < .01) and from 0.44.-k 0.03 to 0.60 ± 0.03 (P < .05), respectively. Systemic changes observed during the SMA occlusion were reduction of cardiac index (161 ± 12 to 114 ± 8 mL/min/kg, P < .01) and pulmonary capillary wedge pressure (4 ± 1 to 3 ± 1 mm Hg) and increase in heart rate (124 ± 5 to 173 ± 11 beats/ min, P < .01) and mean arterial pressure (79 ± 3 to 104 ± 5 mm Hg, P < .01). Systemic oxygen extraction increased (P < .05), arterial pH increased (P < .05), and arterial lactate decreased (P < .01) during the SMA occlusion. Splanchnic ischemia defined as an increase in portal vein-arterial lactate gradient above mean +2 SD of the baseline occurred at 93 ± 15 minutes corresponding 70% SMA occlusion. We conclude that signs of tissue hypoperfusion started to develop at 70% SMA occlusion and that regional tissue hypoperfusion in the splanchnic region may develop without any systemic signs of oxygen supply/demand mismatch.     

Conducting case study research in occupational therapy

Background:  Case study research has been used increasingly in psychology and sociology in recent years. It provides researchers with an opportunity to explore a situation involving one individual or several individuals over time from multiple points of view.
Methods:  This literature review explains case study research as a method and summerises its scientific merit, also providing an example of its use.
Results:  Case study research offers occupational therapists a scientific methodology that can be used to understand and develop occupational therapy practice.
Conclusion:  This paper argues that case study research should be used more extensively by occupational therapists as the method respects the basic principles of occupational therapy.