Mitochondrial genetic background plays a role in increasing risk to asthma

A number of studies suggest that mitochondrial dysfunction plays a role in the pathogenesis of asthma. To shed light for the first time on the role of the mitochondrial genome in the etiology of asthma we analyzed the mitochondrial tRNA genes and part of their flanking regions in patients with asthma compared with a set of healthy controls. We found a total of 10 mutations in 56 out of 76 asthmatic patients. Four of these mutations were not found in the control group, five were observed at a significantly lower frequency in controls, but none of the combinations of mutations detected in asthma patients was observed in the controls. Furthermore, we observed that 27.6% of the asthma patients (vs. 4% of the controls) belonged to the haplogroup U (Fisher test P = 0.00) and a positive significant correlation was found between the occurrence of the haplogroup U and the severity of the disease (Fisher test P = 0.02). Whereas further studies in larger cohorts are needed to confirm these observations we suggest that the mitochondrial genetic background plays a key role in asthma development.     

Myocardial infarction and intramyocardial injection models in swine

Sustainable and reproducible large animal models that closely replicate the clinical sequelae of myocardial infarction (MI) are important for the translation of basic science research into bedside medicine. Swine are well accepted by the scientific community for cardiovascular research, and they represent an established animal model for preclinical trials for US Food and Drug Administration (FDA) approval of novel therapies. Here we present a protocol for using porcine models of MI created with a closed-chest coronary artery occlusion-reperfusion technique. This creates a model of MI encompassing the anteroapical, lateral and septal walls of the left ventricle. This model infarction can be easily adapted to suit individual study design and enables the investigation of a variety of possible interventions. This model is therefore a useful tool for translational research into the pathophysiology of ventricular remodeling and is an ideal testing platform for novel biological approaches targeting regenerative medicine. This model can be created in approximately 8-10 h.     

Molecular Dynamics as a pattern recognition tool: an automated process detects peptides that preserve the 3D arrangement of Trypsin's Active Site

Recently, the synthesis of a molecule has been reported that belongs to a Lysine based, branched cyclic peptide class. This work explores the ability of such molecules to preserve the 3D geometry of the Trypsin's Active Site (TAS) by applying an integrated framework of automated computer procedures. The following four factors a) D/L chirality, b) different amino acids at different positions of the molecular scaffold's cyclic part, c) the application of AMBER and CHARMM force fields and d) different implicit solvation models were evaluated against TAS similarity. It was found that a number of molecules exhibit satisfactory geometric affinity to the TAS during extended Molecular Dynamics runs. We estimated that more than 2000 molecules (belonging to this class) could retain good similarity to the TAS arrangement.     

A Thermodynamic Funnel Drives Bacterial Lipopolysaccharide Transfer in the TLR4 Pathway

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Simultaneous bilateral posteromedial tibial epiphysis stress fractures in a healthy young man: A case report

We present a compelling case of simultaneous, bilateral tibial stress fractures occurring in a unique epiphyseal and posterior location, with unclear aetiology. An overweight, Caucasian male in his late 20s developed synchronous bilateral medial knee pain following an intense 10-day training regimen. His radiographies were normal, but MRI revealed almost identical bilateral stress fracture lines in the posteromedial tibial epiphyses. Bone mineral densitometry and a full metabolic and hormonal panel were performed to further investigate potential underlying metabolic bone disease. He was found to have normal bone mineral densitometry and low Vitamin D serum values. Symptomatology greatly improved with activity modification. There were no further complaints and complications at 12 months’ follow-up. Diagnosis can be challenging and the treating physician should be acquainted with the basic science of stress fractures and main discriminating clinical, biochemical and radiological characteristics from insufficiency fractures, to avoid pitfalls in treatment decision.     

Phosphorylated ERM is responsible for increased T cell polarization, adhesion, and migration in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune/inflammatory disease characterized by autoantibody production and abnormal T cells that infiltrate tissues through not well-known mechanisms. We report that SLE T lymphocytes display increased levels of CD44, ezrin, radixin, and moesin (ERM) phosphorylation, stronger actin polymerization, higher polar cap formation, and enhanced adhesion and chemotactic migration compared with T cells from patients with rheumatoid arthritis and normal individuals. Silencing of CD44 by CD44 small interfering RNA in SLE T cells inhibited significantly their ability to adhere and migrate as did treatment with Rho kinase and actin polymerization inhibitors. Forced expression of T567D-ezrin, a phosphorylation-mimic form, enhanced remarkably the adhesion and migration rate of normal T cells. Anti-CD3/TCR autoantibodies present in SLE sera caused increased ERM phosphorylation, adhesion, and migration in normal T cells. pERM and CD44 are highly expressed in T cells infiltrating in the kidneys of patients with lupus nephritis. These data prove that increased ERM phosphorylation represents a key molecular abnormality that guides T cell adhesion and migration in SLE patients.     

Percutaneous treatment of spontaneous left main coronary artery dissection using drug-eluting stent

Background

Previous studies indicated that the clustering of major cardiovascular disease (CVD) risk factors is common, and multiple unhealthy lifestyles are responsible for the clustering of CVD risk factors. However, little is known about the direct association between the volume load and the clustering of CVD risk factors in general population.

Methods

We investigated the association of the clustering of CVD risk factors (defined as two or more of the following factors: hypertension, diabetes, dyslipidemia and overweight) with volume load, which was evaluated by bioelectrical impedance analysis. Hypovolaemia was defined as extracellular water/total body water (ECW/TBW) at and under the 10th percentile for the normal population.

Results

Among the 7900 adults, only 29.3% were free of any pre-defined CVD risk factors and 40.8% had clustering of CVD risk factors. Hypovolaemia in clustering group was statistically higher than that either in the single or in the none risk factor group, which was 23.7% vs. 17.0% and 10.0%, respectively (P <0.001). As a categorical outcome, the percentage of the lowest quartiles of ECW/TBW and TBW/TBWwatson in clustering group were statistically higher than either those in the single or in the none risk factor group, which were 44.9% vs. 36.9% and 25.1% (P <0.001), 36.2% vs. 32.2% and 25.0%, respectively (P <0.001). After adjusting of potential confounders, hypovolaemia was significantly associated with clustering of CVD risk factors, with an OR of 1.66 (95% CI, 1.45-1.90).

Conclusions

Hypovolaemia was associated with clustering of major CVD risk factors, which further confirms the importance of lifestyle for the development of CVD.

     

Books Average Previous Decade of Economic Misery

For the 20^th century since the Depression, we find a strong correlation between a ‘literary misery index’ derived from English language books and a moving average of the previous decade of the annual U.S. economic misery index, which is the sum of inflation and unemployment rates. We find a peak in the goodness of fit at 11 years for the moving average. The fit between the two misery indices holds when using different techniques to measure the literary misery index, and this fit is significantly better than other possible correlations with different emotion indices. To check the robustness of the results, we also analysed books written in German language and obtained very similar correlations with the German economic misery index. The results suggest that millions of books published every year average the authors'' shared economic experiences over the past decade.