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Aims: General obesity, measured by body mass index (BMI), and abdominal adiposity, measured as waist circumference (WC) and waist-to-hip ratio (WHR), are associated with heart failure and cardiovascular events. However, the relationship of general and abdominal obesity with subclinical left ventricular (LV) dysfunction is unknown. We assessed the association of general and abdominal obesity with subclinical LV systolic dysfunction in a population-based elderly cohort., Methods and Results: Participants from the Cardiovascular Abnormalities and Brain Lesions study underwent measurement of BMI, WC, and WHR. Left ventricular systolic function was assessed by two-dimensional echocardiographic LV ejection fraction (LVEF) and speckle-tracking global longitudinal strain (GLS). The study population included 729 participants (mean age 71 ± 9 years, 60% women). In multivariate analysis, higher BMI (but not WC and WHR) was associated with higher LVEF (β = 0.11, P = 0.003). Higher WC (β = 0.08, P = 0.038) and higher WHR (β = 0.15, P < 0.001) were associated with lower GLS, whereas BMI was not (P = 0.720). Compared with normal WHR, high WHR was associated with lower GLS in all BMI categories (normal, overweight, and obese), and was associated with subclinical LV dysfunction by GLS both in participants without [adjusted odds ratio (OR) 2.0, 95% confidence interval (CI) 1.1-3.6, P = 0.020] and with general obesity (adjusted OR 5.4, 95% CI 1.1-25.9, P = 0.034). WHR was incremental to BMI and risk factors in predicting LV dysfunction., Conclusion: Abdominal adiposity was independently associated with subclinical LV systolic dysfunction by GLS in all BMI categories. BMI was not associated with LV dysfunction. Increased abdominal adiposity may be a risk factor for LV dysfunction regardless of the presence of general obesity., (© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.)

Background and Purpose: Prostamides are lipid mediators formed by COX-2-catalysed oxidation of the endocannabinoid anandamide and eliciting effects often opposed to those caused by anandamide. Prostamides may be formed when hydrolysis of anandamide by fatty acid amide hydrolase (FAAH) is physiologically, pathologically or pharmacologically decreased. Thus, therapeutic benefits of FAAH inhibitors might be attenuated by concomitant production of prostamide F2 α . This loss of benefit might be minimized by compounds designed to selectively antagonize prostamide receptors and also inhibiting FAAH., Experimental Approach: Inhibition of FAAH by a series of selective antagonists of prostamide receptors, including AGN 204396, AGN 211335 and AGN 211336, was assessed using rat, mouse and human FAAH in vitro, together with affinity for human recombinant CB1 and CB2 receptors. Effects in vivo were measured in a model of formalin-induced inflammatory pain in mice., Key Results: The prostamide F2 α receptor antagonists were active against mouse and rat FAAH in the low μM range and behaved as non-competitive and plasma membrane-permeant inhibitors. AGN 211335, the most potent inhibitor of rat FAAH (IC50  = 1.2 μM), raised exogenous anandamide levels in intact cells and also bound to cannabinoid CB1 receptors. Both AGN 211335 and AGN 211336 (0.25-1 mg·kg(-1) , i.p.) inhibited the formalin-induced nociceptive response in mice., Conclusions and Implications: Synthetic compounds with indirect agonist activity at cannabinoid receptors and antagonist activity at prostamide receptors can be developed. Such compounds could be used as alternatives to selective FAAH inhibitors to prevent the possibility of prostamide F2 α -induced inflammation and pain., Linked Articles: This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6., (© 2013 The British Pharmacological Society.)

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohorts

Background: Little is known about gallbladder motility in patients with black pigment stones when compared to cholesterol gallstone patients, or about their relationship to biliary composition, crystallization and stone characteristics., Design: Fasting and postprandial gallbladder volumes were studied by ultrasonography in 49 gallstone patients with pigment (n = 14) or cholesterol (n = 35) stones and 30 healthy controls. After cholecystectomy stone composition, gallbladder wall inflammation, cholesterol saturation index and appearance of platelike cholesterol crystals in bile were evaluated in gallstone patients., Results: Fasting gallbladder volume was significantly (P < 0.05) increased in cholesterol stone patients (31.7 +/- 1.9 mL) but not in pigment stone patients (21.9 +/- 3.1 mL), compared to controls (21.0 +/- 1.5 mL). Postprandial emptying was delayed in patients (half-emptying time: 31 +/- 2 min, 35 +/- 3 min, 24 +/- 2 min in cholesterol stone patients, pigment stone patients and controls, respectively, P < 0.05) and incomplete (residual volume: 43.2 +/- 2.7%, 40.0 +/- 4.3%, 15.8 +/- 1.6% min in cholesterol stone patients, pigment stone patients and controls, respectively, P < 0.05). The inflammation of the gallbladder wall was mild or absent in all cases. Biliary cholesterol saturation index was 152.3 +/- 8.5% and 92.9 +/- 4.8% in patients with cholesterol and pigment stones, respectively (P < 0.01). Whereas cholesterol crystals never appeared during 21 days in biles from patients with pigment stones, crystal observation time in patients with cholesterol gallstone was 5 days (median) and was significantly shorter in patients with multiple (4 days) than in patients with solitary (12 days) cholesterol stones (P = 0.0019)., Conclusions: Patients with black pigment stones who do not have excess cholesterol and do not grow cholesterol crystals in bile have decreased gallbladder emptying, although to a lesser extent than patients with cholesterol stones. Thus, gallbladder stasis is likely to put a subset of subjects at risk for the formation of pigment gallstones, and pathogenic mechanisms need to be further investigated.

Streaming potentials (SPs) measured in vivo at a specific site on intact cortical bone (canine tibia) have been compared with measurements from the same site in vitro, tested as an excised bone strip soaked in Hank's balanced salt solution. The amplitude of SPs per periosteal strain in vitro was larger in 13 tibias than in vivo (by an average x6.5 at 1 Hz), but values per transcortical strain difference were similar. In vitro, SP magnitudes rose more sharply to an asymptotic value as a function of bending frequency than did in vivo signals, possibly because of a difference in the internal state of canaliculi and/or Haversian systems. Similarly, SP response to step-loading decreased to zero more slowly with time in vitro than in vivo. Difficulties encountered in preliminary measurements due to electrical shunting through electrolyte and soft tissues suggest the need for caution in using both in vivo and in vitro SP measurements to extrapolate to electric field strengths on the cellular level.

Prototype testing has been accomplished on a piezoelectric, internal fixation plate. This device combines a piezoelectric material with an internal fixation device as an integrated structure that provides mechanical stability, together with self-generated electrical stimulation, for treating fractures and nonunion. In bench and animal tests we have demonstrated that cyclical loading can cause a device of this type to generate electrical charge while attached to bone. After rectification, direct currents within the range known to stimulate osteogenesis can be produced by weight-bearing loads. Furthermore, electrical output of the implants can be increased by externally applied ultrasonic energy. These twin developments add significantly to the potential armamentarium of devices to enhance bone healing.

Under development is an internal fixation plate that incorporates a piezoelectric element to generate current when excited mechanically by either weight bearing or external application of ultrasound. The intent is to deliver this current to electrodes at a fracture or osteotomy site to aid in prevention or treatment of nonunion. The present study examines quantitatively the ability of external ultrasound to generate current from small piezoelectric ceramic elements implanted in tissue. An ultrasonic transducer (2.25 MHz, 10-20 V input, less than 10 mW/cm2 output) was employed to excite small test coupons of a piezoelectric ceramic in vitro and in vivo with various materials, including water, PVC gel, cortical bone, and living soft tissues, interposed. In all instances, it was possible to generate currents of up to 20 microA after rectification; currents up to 1 mA were achieved in some cases. The work indicates that external ultrasonic energy could effectively power small internal devices designed to stimulate bone healing, without the need for implanted batteries or percutaneous leads.