Massive left atrium thrombus

The image shows a left atrium completely occupied by a giant non-homogeneous, irregularly-surfaced mass, obstructing the disc motion, mimicking severe mitral prosthetic stenosis.     

Reverse or inverted apical ballooning in a case of refeeding syndrome

Takotsubo cardiomyopathy is characterized by the development of transient left ventricular regional wall motion abnormalities, in the absence of significant coronary artery obstruction. This syndrome usually occurs in women and is frequently associated with an intense emotional or physical stress. It usually involves apical segments, but in the recent years atypical forms have been described. Inverted or reverse Takotsubo is a variant in which the basal and midventricular segments are hypokinetic, sparing contractile function of the apex. In this report we describe the case of a 54-year-old woman, with chronic malnutrition, initially admitted because of hypoglycemia and severe electrolyte disturbance due to a refeeding syndrome. Within the next hours she experienced acute cardiac symptoms and developed heart failure with low cardiac output. Electrocardiogram (ECG), elevation of troponin and echocardiographic findings were consistent with inverted Takotsubo cardiomyopathy. To the best of our knowledge, this is the first incidence reported of inverted Takotsubo triggered by refeeding syndrome.     

Surfactant Protein D, a Marker of Lung Innate Immunity, Is Positively Associated With Insulin Sensitivity

OBJECTIVE

Impaired lung function and innate immunity have both attracted growing interest as a potentially novel risk factor for glucose intolerance, insulin resistance, and type 2 diabetes. We aimed to evaluate whether surfactant protein D (SP-D), a lung-derived innate immune protein, was behind these associations.

RESEARCH DESIGN AND METHODS

Serum SP-D was evaluated in four different cohorts. The cross-sectional associations between SP-D and metabolic and inflammatory parameters were evaluated in two cohorts, the cross-sectional relationship with lung function in one cohort, and the longitudinal effects of weight loss on fasting and circadian rhythm of serum SP-D and cortisol concentrations in one prospective cohort.

RESULTS

In the cross-sectional studies, serum SP-D concentration was significantly decreased in subjects with obesity and type 2 diabetes (P = 0.005) and was negatively associated with fasting and postload serum glucose. SP-D was also associated with A1C, serum lipids, insulin sensitivity, inflammatory parameters, and plasma insulinase activity. Smoking subjects with normal glucose tolerance, but not smoking patients with type 2 diabetes, showed significantly higher serum SP-D concentration than nonsmokers. Serum SP-D concentration correlated positively with end-tidal carbon dioxide tension (r = 0.54, P = 0.034). In the longitudinal study, fasting serum SP-D concentration decreased significantly after weight loss (P = 0.02). Moreover, the main components of cortisol and SP-D rhythms became synchronous after weight loss.

CONCLUSIONS

These findings suggest that lung innate immunity, as inferred from circulating SP-D concentrations, is at the cross-roads of inflammation, obesity, and insulin resistance.Impaired lung function has attracted growing interest in association with metabolic disorders (1–6). Decreased lung function has been proposed as a potential novel risk factor for glucose intolerance, insulin resistance, and type 2 diabetes (1–6). In prospective studies of middle-aged men and women without known lung disease, lower vital capacity predicted the subsequent development of type 2 diabetes. Lower forced vital capacity and forced expiratory volume in 1 s at baseline predicted hyperinsulinemia and estimated insulin resistance over 20 years of follow-up, independent of age, adiposity, and smoking (1).Possible mechanisms for the hypothesized link include direct effects of hypoxemia on glucose and insulin regulation (7), adverse early-life exposures and their effects on organ development (8), and lung-related inflammatory mediators and their effects on insulin signaling (9). In fact, nuclear factor interleukin-6, early growth response-1, and hypoxia-inducible factor-1 mediate inflammatory responses to chronic hypoxia in macrophages, pulmonary vascular endothelium, and smooth muscle (6,9). Cigarette smoking, an independent predictor of type 2 diabetes (10), provokes an inflammatory response (11) and is inversely associated with vital capacity. However, the link between lower vital capacity and diabetes risk was completely independent of cigarette exposure and was stronger in never-smokers (6).Reduced vital capacity is a common residual effect of lower respiratory tract infections, including those in childhood and infancy (8), that might provoke an inflammatory response. A reduced ability to sense and eradicate pathogens could thus cause frequent respiratory tract infections, reduced vital capacity, and chronic inflammation resulting in insulin resistance and type 2 diabetes (12). The total incidence rate of infections needing hospitalization in diabetic patients was 41/1,000 persons-years compared with 16/1,000 person-years of follow-up in the general population. Roughly half of the infections were severe lung infections, suggesting impaired lung immunity in patients with type 2 diabetes (13).Pulmonary surfactant is a complex mixture of lipids (90%) and proteins (5–10%) that constitutes the mobile liquid phase covering the large surface area of the alveolar epithelium. It maintains minimal surface tension within the lungs to avoid lung collapse during respiration. The innate immune system, by upregulating SP-D synthesis, can immediately respond to intrusion of foreign agents by helping to prevent further invasion (14). This recognition is important in the day-to-day physiology. Each day, we breathe >7,000 liters of air, laden with inorganic and organic particles and an array of microbes. Secreted primarily by alveolar epithelial type II pneumocytes, plasma SP-D appears to increase early in the clinical course of lung injury, and its concentration is thought to reflect pulmonary epithelial injury (15).Subtle deficiencies in proteins of the sensing arm of the innate immune system have been found to be associated with alterations of glucose metabolism. These deficiencies run in parallel with inflammation and impaired insulin action (16).We hypothesized that SP-D could be behind the association of lung function with impaired insulin action. For that reason, we aimed to evaluate SP-D according to metabolic and inflammatory parameters. As SP-D was associated with obesity status and impaired glucose metabolism, we evaluated the influence of weight loss on both fasting and circadian serum SP-D concentration. As glucocorticoids seem to regulate SP-D production in in vitro studies (17), we investigated the influence of circadian cortisol rhythm on serum SP-D concentration. Finally, we also studied the association of SP-D with lung function tests.     

Comparative analysis of genetic modifiers in Drosophila points to common and distinct mechanisms of pathogenesis among polyglutamine diseases

Spinocerebellar Ataxia type 1 (SCA1) and Huntington's disease (HD) are two polyglutamine disorders caused by expansion of a CAG repeat within the coding regions of the Ataxin-1 and Huntingtin proteins, respectively. While protein folding and turnover have been implicated in polyglutamine disorders in general, many clinical and pathological differences suggest that there are also disease-specific mechanisms. Taking advantage of a collection of genetic modifiers of expanded Ataxin-1-induced neurotoxicity, we performed a comparative analysis in Drosophila models of the two diseases. We show that while some modifier genes function similarly in SCA1 and HD Drosophila models, others have model-specific effects. Surprisingly, certain modifier genes modify SCA1 and HD models in opposite directions, i.e. they behave as suppressors in one case and enhancers in the other. Furthermore, we find that modulation of toxicity does not correlate with alterations in the formation of neuronal intranuclear inclusions. Our results point to potential common therapeutic targets in novel pathways, and to genes and pathways responsible for differences between Ataxin-1 and Huntingtin-induced neurodegeneration.     

Reduction of female-directed song motifs induced by repeated singing in laboratory-bred zebra finches

Songbirds such as zebra finches show a remarkable degree of neural plasticity associated with the motor act of singing. Here we show that in adult male zebra finches repeated female-directed singing episodes are associated with a change in subsequent singing behavior involving a progressive long-lasting decline in the number of song motifs sung. This reduction in song motif production cannot be completely explained by the circadian rhythm, declining motivation or neuromuscular exhaustion. Paired song induction sessions reveal that the time course of motif reduction during repeated singing can be best explained by the cumulative effect of reduction produced by each singing episode. These results suggest that song production in zebra finches is prone to a form of rapid behavioral adaptation.     

Adiponectin, hepatocellular dysfunction and insulin sensitivity

OBJECTIVE: Insulin resistance plays a major aetiological role in the development of fatty liver disease. Because adiponectin is a hepatic insulin sensitizer and also an inhibitor of tumour necrosis factor, a cytokine known to induce insulin resistance and liver damage, we wished to study whether low circulating adiponectin would be associated with higher serum concentrations of liver enzymes in healthy subjects. DESIGN: Cross-sectional, population-based study dealing with diabetes prevalence in northern Spain. PATIENTS: Two hundred and fifty-seven apparently healthy Caucasian subjects consecutively enrolled in the study. MEASUREMENTS: Adiponectin serum levels were measured by enzyme-linked immunosorbent assay (ELISA), liver function tests (LFTs) by colourimetry and insulin resistance by the homeostasis model of assessment (HOMA value). RESULTS: Adiponectin levels were negatively correlated with alanine aminotransferase (ALT) and gamma-glutamyltranspeptidase (GGT), before and after adjustment for sex, age, body mass index (BMI) and insulin resistance (ALT; r = -0.32, P < 0.001; adjusted: r = -0.13, P = 0.033; GGT; r = -0.31, P < 0.001; adjusted: r = -0.16, P = 0.011). Additionally, adiponectin correlated with alkaline phosphate (ALKP) only after adjusting for the same confounding variables (r =-0.10, P = 0.098; adjusted: r = -0.14, P = 0.031). A general linear model, adjusting for age, sex and BMI, was constructed to predict the decrease in circulating adiponectin for each LFT value (i.e. ALT, GGT and ALKP) above the median. Beyond one LFT value above the median, serum adiponectin decreased by -0.97 mg/l (95% CI -1.46 to -0.48). In multiple regression analysis, sex, BMI and adiponectin, but not insulin resistance, predicted serum concentrations of both ALT and GGT, explaining 19% and 14% of their variance, respectively. Age, BMI and adiponectin, but not sex or insulin resistance, explained 20% of ALKP variance. CONCLUSIONS: Adiponectin levels are associated in healthy humans with plasma concentrations of various liver function tests. The contributions of adiponectin to maintaining liver integrity through the regulation of both insulin sensitivity and/or the inflammatory response merit further studies.     

Development and adult phase plasticity of syllable repetitions in the birdsong of captive zebra finches (Taeniopygia guttata)

Oscines learn their birdsongs from tutors. The authors found that a small fraction (approximately 7%) of captive male zebra finches (Taeniopygia guttata) produce variant acoustic birdsong profiles consisting of repetitions of single song syllables at high frequencies. Juvenile offspring of nonrepeaters can selectively learn the syntactic rule or habit of repeating syllables from repeaters. Adult tutored syllable repeaters, unlike spontaneous repeaters, undergo a form of song plasticity involving progressive reduction of the mean number and variance of repeated syllables as a function of long-term exposure to nonrepeater songs without altering the number or sequence of syllables within motifs. These findings suggest that aspects of song syntax or temporal frame can be acquired independently of song syllable or spectral content, and plasticity involving restorative alteration of acquired variant temporal frames can occur after the closure of the critical period for song learning.