Atrial function in the Fontan circulation: comparison with invasively assessed systemic ventricular filling pressure

The International Journal of Cardiovascular Imaging - Abnormal atrial mechanics in biventricular circulations have been associated with elevated left heart filling pressures. Similar associations...     

Inferior glenohumeral joint dislocation with greater tuberosity avulsion

Inferior glenohumeral dislocation is the least common type of glenohumeral dislocations. It may be associated with fractures of the adjacent bones and neurovascular compromise. It should be treated immediately by close reduction. The associated neuropraxia usually recovers with time. Traction-counter traction method is commonly used for reduction followed by immobilization of the shoulder for three weeks. Here, we report a case of inferior glenohumeral joint dislocation with greater tuberosity fracture with transient neurovascular compromise and present a brief review of the literature.     

Lipoprotein status among urban populations in Bangladesh

ObjectiveSerum lipoprotein is the most important predictor for microvascular diseases, and may be influenced by rapid urbanization. Currently available data are limited, particularly regarding age-specific lipoprotein status in urban Bangladeshi populations.MethodsBlood lipoprotein levels of 51,353 male and female individuals primarily residing in urban Bangladesh were analyzed. De-identified data (collected between January 2005 and December 2011) were extracted from the Clinical Biochemistry Laboratory Data Archive of International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). For analyses, six age categories were created: (i) <20 years, n = 481; (ii) 20–29 years, n = 1602; (iii) 30–39 years, n = 7272; (iv) 40–49 years, n = 13,582; (v) 50–59 years, n = 15,890; and (vi) 60 years and more, n = 12,526.ResultsMean serum levels of TC, LDL, TG, LDL:HDL and TC:HDL were significantly higher among adults 30–39 years old compared to other age groups, regardless of sex. The proportion of high TC and LDL from 2005 to 2011 among individuals aged 30–39 years old varied widely (p < 0.01 for trend and all pairwise tests).Conclusion30–39 years old individuals had higher concentration of lipoprotein, which increases microvascular disease risk. Further population-based studies are needed to validate our observations in rural areas of Bangladesh.     

Skeletal Muscle Triacylglycerol Hydrolysis Does Not Influence Metabolic Complications of Obesity

Intramyocellular triacylglycerol (IMTG) accumulation is highly associated with insulin resistance and metabolic complications of obesity (lipotoxicity), whereas comparable IMTG accumulation in endurance-trained athletes is associated with insulin sensitivity (the athlete’s paradox). Despite these findings, it remains unclear whether changes in IMTG accumulation and metabolism per se influence muscle-specific and systemic metabolic homeostasis and insulin responsiveness. By mediating the rate-limiting step in triacylglycerol hydrolysis, adipose triglyceride lipase (ATGL) has been proposed to influence the storage/production of deleterious as well as essential lipid metabolites. However, the physiological relevance of ATGL-mediated triacylglycerol hydrolysis in skeletal muscle remains unknown. To determine the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes in the context of obesity, we generated mice with targeted deletion or transgenic overexpression of ATGL exclusively in skeletal muscle. Despite dramatic changes in IMTG content on both chow and high-fat diets, modulation of ATGL-mediated IMTG hydrolysis did not significantly influence systemic energy, lipid, or glucose homeostasis, nor did it influence insulin responsiveness or mitochondrial function. These data argue against a role for altered IMTG accumulation and lipolysis in muscle insulin resistance and metabolic complications of obesity.Obesity is a global public health problem and a major risk factor for insulin resistance and type 2 diabetes. These disorders are characterized by excess lipid accumulation in multiple tissues, primarily as triacylglycerols (TAGs). The lipotoxicity hypothesis suggests that this lipid excess promotes cellular dysfunction and cell death, which ultimately contribute to insulin resistance and metabolic disease (1). However, intracellular TAG accumulation is not always associated with adverse metabolic outcomes, suggesting that TAGs themselves are not pathogenic (2). In contrast, other non-TAG lipid metabolites such as fatty acids (FAs), diacylglycerols (DAGs), and ceramides have been shown to influence glucose homeostasis and insulin action by interfering with insulin signaling and glucose transport, promoting endoplasmic reticulum stress and mitochondrial dysfunction, and activating inflammatory and apoptotic pathways (reviewed in ref. 3). Nevertheless, the precise identities and sources of these bioactive lipid intermediates remain elusive (4,5). Furthermore, whether intracellular TAGs serve as a protective sink or a toxic source of deleterious lipid metabolites that contribute to insulin resistance remains unclear (6).Since skeletal muscle is the major contributor to insulin-mediated glucose disposal, lipid excess in this tissue could have serious implications for systemic glucose homeostasis and insulin responsiveness (7). Indeed, numerous studies have demonstrated a strong association between intramyocellular triacylglycerol (IMTG) accumulation and insulin resistance (reviewed in ref. 8). In contrast, endurance exercise training is characterized by IMTG accumulation and insulin sensitivity (the athlete’s paradox) (2). This variable association between IMTG accumulation and insulin responsiveness has largely been attributed to differences in the balance between lipid delivery and muscle oxidative capacity (8–10). Not surprisingly then, most studies have focused on the impact of muscle FA uptake and/or oxidation on glucose homeostasis and insulin action (11). However, experimental manipulations of these parameters cannot distinguish among the effects of IMTGs, IMTG metabolism, and other lipid intermediates. Furthermore, accumulating evidence suggests that muscle oxidative capacity cannot entirely explain differences in IMTGs or insulin responsiveness (12). These findings have led to speculation that dynamic IMTG metabolism (i.e., TAG synthesis or hydrolysis) may be critically involved in lipid-induced insulin resistance (6). However, few studies have specifically addressed the contribution of IMTG metabolism per se to this process.The regulated storage and release of IMTGs remain poorly understood, but require the coordinated action of synthetic enzymes (i.e., diacylglycerol acyltransferases [DGATs]), hydrolytic enzymes (i.e., adipose triglyceride lipase [ATGL] and hormone sensitive lipase [HSL]), and other lipid droplet proteins (6). Specifically, modulating IMTG synthesis in murine skeletal muscle alters IMTG content and systemic glucose homeostasis, supporting a role for IMTG metabolism in metabolic disease (13–15). However, the metabolic impact of modulating IMTG hydrolysis in vivo remains unclear. Global deletion of either ATGL (16–19) or HSL (20) has produced variable results. The former, but not the latter, results in massive IMTG accumulation with improvement in systemic glucose homeostasis, suggesting that inhibition of ATGL-mediated TAG hydrolysis protects against insulin resistance. In contrast, recent studies in cardiac muscle (21) and other tissues (22,23) indicate that ATGL-mediated TAG hydrolysis is required for mitochondrial function such that enhancing, rather than inhibiting, ATGL action may improve metabolic outcomes. Nevertheless, the autonomous role of skeletal muscle TAG catabolism in influencing muscle-specific and systemic metabolic phenotypes remains unknown.The goal of the current study was to understand the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes, particularly glucose homeostasis and insulin action, in the context of obesity. We therefore generated animal models with decreased (skeletal muscle-specific ATGL knockout [SMAKO] mice) and increased (muscle creatine kinase [Ckm]-ATGL transgenic [Tg] mice) ATGL action exclusively in skeletal muscle, and assessed the metabolic consequences at baseline and in response to chronic high-fat feeding. Interestingly, modulation of IMTG hydrolysis via ATGL action did not significantly influence glucose homeostasis, insulin action, or other metabolic phenotypes in the context of obesity despite dramatic changes in IMTG content.     

Outcomes of transcutaneous nerve stimulation for migraine headaches: a systematic review and meta-analysis

Journal of Neurology - Implanted and transcutaneous nerve stimulators have shown promise as novel non-pharmacologic treatment for episodic and chronic migraines. The purpose of this study was to...     

Hypercapnia modulates cAMP signalling and cystic fibrosis transmembrane conductance regulator‐dependent anion and fluid secretion in airway epithelia

Key points

• Raised arterial blood CO₂ (hypercapnia) is a feature of many lung diseases.
• CO₂ has been shown to act as a cell signalling molecule in human cells, notably by influencing the levels of cell signalling second messengers: cAMP and Ca²⁺.
• Hypercapnia reduced cAMP‐stimulated cystic fibrosis transmembrane conductance regulator‐dependent anion and fluid transport in Calu‐3 cells and primary human airway epithelia but did not affect cAMP‐regulated HCO₃ ⁻ transport via pendrin or Na⁺/HCO₃ ⁻ cotransporters.
• These results further support the role of CO₂ as a cell signalling molecule and suggests CO₂‐induced reductions in airway anion and fluid transport may impair innate defence mechanisms of the lungs.

Abstract

Hypercapnia is clinically defined as an arterial blood partial pressure of CO₂ of above 40 mmHg and is a feature of chronic lung disease. In previous studies we have demonstrated that hypercapnia modulates agonist‐stimulated cAMP levels through effects on transmembrane adenylyl cyclase activity. In the airways, cAMP is known to regulate cystic fibrosis transmembrane conductance regulator (CFTR)‐mediated anion and fluid secretion, which contributes to airway surface liquid homeostasis. The aim of the current work was to investigate if hypercapnia could modulate cAMP‐regulated ion and fluid transport in human airway epithelial cells. We found that acute exposure to hypercapnia significantly reduced forskolin‐stimulated elevations in intracellular cAMP as well as both adenosine‐ and forskolin‐stimulated increases in CFTR‐dependent transepithelial short‐circuit current, in polarised cultures of Calu‐3 human airway cells. This CO₂‐induced reduction in anion secretion was not due to a decrease in HCO₃ ⁻ transport given that neither a change in CFTR‐dependent HCO₃ ⁻ efflux nor Na⁺/HCO₃ ⁻ cotransporter‐dependent HCO₃ ⁻ influx were CO₂‐sensitive. Hypercapnia also reduced the volume of forskolin‐stimulated fluid secretion over 24 h, yet had no effect on the HCO₃ ⁻ content of the secreted fluid. Our data reveal that hypercapnia reduces CFTR‐dependent, electrogenic Cl⁻ and fluid secretion, but not CFTR‐dependent HCO₃ ⁻ secretion, which highlights a differential sensitivity of Cl⁻ and HCO₃ ⁻ transporters to raised CO₂ in Calu‐3 cells. Hypercapnia also reduced forskolin‐stimulated CFTR‐dependent anion secretion in primary human airway epithelia. Based on current models of airways biology, a reduction in fluid secretion, associated with hypercapnia, would be predicted to have important consequences for airways hydration and the innate defence mechanisms of the lungs.     

A framework for testing the equality between the health concentration curve and the 45‐degree line

The health concentration curve is the standard graphical tool to depict socioeconomic health inequality in the literature on health inequality. This paper shows that testing for the absence of socioeconomic health inequality is equivalent to testing if the conditional expectation of health on income is a constant function that is equal to average health status. In consequence, any test for parametric specification of a regression function can be used to test for the absence of socioeconomic health inequality (subject to regularity conditions). Furthermore, this paper illustrates how to test for this equality using a test for parametric regression functional form and applies it to health‐related behaviors from the National Health Survey 2014.     

Effect of SAMe-TT2R2 score and genetic polymorphism on the quality of anticoagulation control in Qatari patients treated with warfarin

Journal of Thrombosis and Thrombolysis - There is no strong evidence on pharmacogenetics role on the quality of INR control after the initiation phase and on the maintenance of stable INR on the...     

A Cognitively Inspired Clustering Approach for Critique-Based Recommenders

Cognitive Computation - The purpose of recommender systems is to support humans in the purchasing decision-making process. Decision-making is a human activity based on cognitive information. In the...