The association between triglyceride to high-density-lipoprotein cholesterol ratio and insulin resistance in a multiethnic primary prevention cohort

The objective was to explore the clinical utility of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio in predicting insulin resistance (IR) in 4 ethnic groups and the relationship between IR and TG/HDL-C in comparison to that with other lipid measures. Apparently healthy Aboriginals, Chinese, Europeans, and South Asians (N = 784) were assessed for sociodemographics, lifestyle, anthropometry, lipids, glucose, and insulin. The homeostasis model assessment of IR was used as a measure of IR. Compared with other lipid parameters, TG/HDL-C was the highest correlate of the homeostasis model assessment of IR (age and sex adjusted) in Aboriginals (r = 0.499, P < .001), Chinese (r = 0.432, P < .001), Europeans (r = 0.597, P < .001), and South Asians (0.372, P < .001). For a 1-unit increase in TG/HDL-C, the odds of being insulin resistant increased about 4 times (odds ratio [OR], 3.95; 95% confidence interval [CI], 1.86-8.42; P < .001) in Aboriginals, 3.4 times in Chinese (OR, 3.44; 95% CI, 1.79-6.62; P < .001), 1.9 times in Europeans (OR, 1.94; 95% CI, 1.00-3.75; P = .049), and 1.8 times in South Asians (OR, 1.77; 95% CI, 0.91-3.45; P = .094) (age, sex, smoking, physical activity, body mass index, and waist circumference adjusted). Receiver operating characteristic curve analyses revealed areas under the curve (95% CI) of 0.777 (0.707-0.847) in Aboriginals, 0.723 (0.647-0.798) in Chinese, 0.752 (0.675-0.828) in Europeans, and 0.676 (0.590-0.762) in South Asians. Optimal cutoffs (sensitivity, specificity) of TG/HDL-C for identifying individuals with IR were 0.9 (93.0%, 51.9%), 1.1 (71.7%, 61.5%), 1.1 (73.5%, 70.9%), and 1.8 (52.0%, 77.9%) in Aboriginal, Chinese, European, and South Asian individuals, respectively. The TG/HDL-C ratio may be a good marker to identify insulin-resistant individuals of Aboriginal, Chinese, and European, but not South Asian, origin.     

Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory pseudosubstrate

The type II p21-activated kinases (PAKs) are key effectors of RHO-family GTPases involved in cell motility, survival, and proliferation. Using a structure-guided approach, we discovered that type II PAKs are regulated by an N-terminal autoinhibitory pseudosubstrate motif centered on a critical proline residue, and that this regulation occurs independently of activation loop phosphorylation. We determined six X-ray crystal structures of either full-length PAK4 or its catalytic domain, that demonstrate the molecular basis for pseudosubstrate binding to the active state with phosphorylated activation loop. We show that full-length PAK4 is constitutively autoinhibited, but mutation of the pseudosubstrate releases this inhibition and causes increased phosphorylation of the apoptotic regulation protein Bcl-2/Bcl-X_L antagonist causing cell death and cellular morphological changes. We also find that PAK6 is regulated by the pseudosubstrate region, indicating a common type II PAK autoregulatory mechanism. Finally, we find Src SH3, but not β-PIX SH3, can activate PAK4. We provide a unique understanding for type II PAK regulation.     

Hypothermic anticoagulation: testing individual responses to graded severe hypothermia with thromboelastography

Selective incircuit blood cooling could be an effective anticoagulation strategy during hemodialysis. However, it is currently unknown what blood temperature would ensure sufficient anticoagulation. Similarly, no information exists about potential interindividual variability in response to graded hypothermia. Therefore, the aim of this study was to analyze effects of profound hypothermia on human coagulation. Furthermore, a mathematical relationship between blood temperatures and coagulation was sought to predict individual responses to blood cooling. It was designed as a laboratory study. Thromboelastography (TEG) measurements were taken at a temperature range of 38-12°C. To enable measurements below 20°C, the TEG device was placed into an air conditioned chamber allowing for setting of the temperatures over a wide range. The data were analyzed by regression analysis for pooled and individual measurements. Decreasing temperatures always led to a progressive reduction in blood coagulation by delaying the initiation of thrombus formation, as well as by decreasing the speed of its creation and growth. However, the response to cooling was not uniform and the interindividual variability exists. The relationship between blood temperature and coagulation is not linear but exponential (parameters R and K) and sigmoid (parameter α-angle). The lower the blood temperature, the more significant effect on blood coagulation decline. To predict an individual response of the coagulation system over a wide range of temperatures, a mathematical modeling can be used.     

Correlation between atmospheric pressure changes and abdominal aortic aneurysm rupture: results of a single-center study

Purpose

There is much interest in all factors that influence the etiopathogenesis of abdominal aortic aneurysm (AAA) rupture. Apart from the well-established factors such as arterial hypertension, smoking, age, and genetic predisposition, less common factors that may play a role in the mechanism of the rupture are the subject of much discussion. These include atmospheric conditions, temperature, and atmospheric pressure. We conducted this study to investigate the effects of the absolute value of atmospheric pressure and its changes on the frequency of AAA rupture.

Methods

We retrospectively examined 54 patients who underwent treatment for a ruptured AAA at the Clinic of Surgery in the University Hospital in Pilsen between 1 January 2005 and 31 December 2009. We collected data on the atmospheric pressure in this period from the Czech Hydrometeorological Institute in Pilsen.

Results

We did not find a significant difference in atmospheric pressure values between the days when the rupture occurred versus the other days (p < 0.5888). Moreover, we did not find significant changes in the atmospheric pressure during the 48 h preceding the rupture (Student’s test p < 0.4434) versus the day of rupture or in the mean atmospheric pressure in that month.

Conclusion

These findings suggest that atmospheric pressure and its changes do not affect the pathogenesis of AAA rupture.