The "athlete's heart" features in amateur male marathon runners.

BACKGROUND: Training on a professional level can lead to cardiac structural adaptations called the "athlete's heart". As marathon participation requires intense physical preparation, the question arises whether the features of "athlete's heart" can also develop in recreational runners. METHODS: The study included 34 males (mean age 40 ± 8 years) who underwent physical examination, a cardiopulmonary exercise test and echocardiographic examination (ECHO) before a marathon. ECHO results were compared with the sedentary control group, reference values for an adult male population and those for highly-trained athletes. Runners with abnormalities revealed by ECHO were referred for cardiac magnetic resonance imaging (CMR). RESULTS: The mean training distance was 56.5 ± 19.7 km/week, peak oxygen uptake was 53.7 ± 6.9 mL/kg/min and the marathon finishing time was 3.7 ± 0.4 h. Compared to sedentary controls, amateur athletes presented larger atria, increased left ventricular (LV) wall thickness, larger LV mass and basal right ventricular (RV) inflow diameter (p < 0.05). When compared with ranges for the general adult population, 56% of participants showed increased left atrial volume, indexed to body surface area (LAVI), 56% right atrial area and interventricular septum thickness, while 47% had enlarged RV proximal outflow tract diameter. In 50% of cases, LAVI exceeded values reported for highly-trained athletes. Due to ECHO abnormalities, CMR was performed in 6 participants, which revealed hypertrophic cardiomyopathy in 1 runner. CONCLUSIONS: "Athlete's heart" features occur in amateur marathon runners. In this group, ECHO reference values for highly-trained elite athletes should be considered, rather than those for the general population and even then LAVI can exceed the upper normal value.

IL-1 Fragment Modulates Immune Response Elicited by Recombinant Bacillus subtilis Spores Presenting an Antigen/Adjuvant Chimeric Protein.

Mucosal immunizations are convenient ways of vaccination, which do not require any trained personnel for administration. One of the major challenges for developing an effective mucosal vaccine is finding appropriate adjuvant. Bacillus subtilis endospores have been shown to help solving these obstacles while serving as a platform for presentation of both, antigens and adjuvants. In this study, we have successfully designed and constructed recombinant spores displaying an antigen/adjuvant chimeric protein. We have used a fragment of Clostridium difficile flagellar cap FliD protein as antigen and VQGEESNDK peptide, a fragment of human IL-1ß, as adjuvant. Recombinant spores presenting FliD were able to elicit immune response in orally immunized mice which could be evaluated by detection of FliD-specific IgA antibodies in feces of immunized animals. Moreover, the presence of IL-1ß fragment significantly changed characteristics of elicited immune response. Obtained results show that recombinant spores presenting an antigen/adjuvant chimeric protein exhibit both properties in mucosal immunization of mice. Moreover, IL-1ß fragment could serve as valuable adjuvant in B. subtilis spore-based mucosal vaccines.

Predictors of poor outcome in patients with pulmonary arterial hypertension: A single center study.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a rare disorder with unfavorable prognosis despite implementation of specific PAH-oriented therapy. The aim of the study was to define predictors of poor prognosis in patients from one center treated according to the Polish National Health Fund program. PATIENTS AND METHODS: Forty-seven consecutive patients (30 women; aged 39±17 years) with PAH diagnosis were enrolled to the study. Clinical assessment, laboratory measurements, electrocardiogram, echocardiography, 6-minute walk test, 24-hour Holter monitoring, cardiopulmonary exercise test and microvolt T-wave alternans test were performed during routine visits. Eight patients died during 2.6±1.7 years follow-up. RESULTS: Parametrs which differentiated patients who died were brain natriuretic peptide (BNP) concentration ≥330 pg/mL (sensitivity 88%, specificity 92%, area under the ROC curve [AUC] 0.92); bilirubin concentration ≥1.2 mg/dL (sensitivity 88%, specificity 81%, AUC 0.85); right atrial area ≥21 cm2 (sensitivity 86%, specificity 69%, AUC 0.84), right ventricular (RV) dimension in the apical 4-chamber view ≥47 mm (sensitivity 86%, specificity 86%, AUC 0.85) and RV to left ventricular diastolic diameter ratio ≥1.5 (sensitivity 83%, specificity 84%; AUC 0.85). In multivariate analysis, independent predictors of mortality were higher BNP (p = 0.04) and bilirubin level (p = 0.03), higher right atrial area (p = 0.02) and lower tricuspid annular plane systolic excursion (p = 0.03). CONCLUSIONS: In PAH patients treated with specific PAH-oriented therapy right atrial enlargement, impaired right ventricular systolic function, as well as increased BNP and bilirubin concentration was associated with an increased mortality risk.

The combination of recombinant and non-recombinant Bacillus subtilis spore display technology for presentation of antigen and adjuvant on single spore.

BACKGROUND: Bacillus subtilis spores can be used for presentation of heterologous proteins. Two main approaches have been developed, the recombinant one, requiring modification of bacterial genome to express a protein of interest as a fusion with spore-coat protein, and non-recombinant, based on the adsorption of a heterologous protein onto the spore. So far only single proteins have been displayed on the spore surface. RESULTS: We have used a combined approach to adsorb and display FliD protein of Clostridium difficile on the surface of recombinant IL-2-presenting spores. Such spores presented FliD protein with efficiency comparable to FliD-adsorbed spores produced by wild-type 168 strain and elicited FliD-specific immune response in intranasally immunized mice. CONCLUSIONS: Our results indicate that such dual display technology may be useful in creation of spores simultaneously presenting adjuvant and antigen molecules. Regarding the characteristics of elicited immune response it seems plausible that such recombinant IL-2-presenting spores with adsorbed FliD protein might be an interesting candidate for vaccine against infections with Clostridium difficile.

Expression and display of Clostridium difficile protein FliD on the surface of Bacillus subtilis spores.

The endospores of Bacillus subtilis can serve as a tool for surface presentation of heterologous proteins. The unique properties of the spore protective layers make them perfect vehicles for orally administered vaccines. In this study, we successfully displayed a fragment of Clostridium difficile FliD protein on the surface of B. subtilis spores using the CotB, CotC, CotG and CotZ spore coat proteins. The presence of the fusion proteins in the spore coat was verified by Western blotting and immunofluorescence microscopy. The amount of recombinant proteins was assessed by a dot-blot technique. C. difficile is one of the most common infectious agents in nosocomial infections and is especially associated with antibiotic therapies. FliD is a flagellar cap protein of C. difficile and is known to be one of the immunogenic surface antigens of this bacterium. Therefore, its use in vaccine formulations gives a good perspective for successful immunization with a FliD-based vaccine. The recombinant spores presented here may be good candidates for C. difficile oral vaccines.

Disruption of ionic interactions between the nucleotide binding domain 1 (NBD1) and middle (M) domain in Hsp100 disaggregase unleashes toxic hyperactivity and partial independence from Hsp70.

Hsp100 chaperones cooperate with the Hsp70 chaperone system to disaggregate and reactivate heat-denatured aggregated proteins to promote cell survival after heat stress. The homology models of Hsp100 disaggregases suggest the presence of a conserved network of ionic interactions between the first nucleotide binding domain (NBD1) and the coiled-coil middle subdomain, the signature domain of disaggregating chaperones. Mutations intended to disrupt the putative ionic interactions in yeast Hsp104 and bacterial ClpB disaggregases resulted in remarkable changes of their biochemical properties. These included an increase in ATPase activity, a significant increase in the rate of in vitro substrate renaturation, and partial independence from the Hsp70 chaperone in disaggregation. Paradoxically, the increased activities resulted in serious growth impediments in yeast and bacterial cells instead of improvement of their thermotolerance. Our results suggest that this toxic activity is due to the ability of the mutated disaggregases to unfold independently from Hsp70, native folded proteins. Complementary changes that restore particular salt bridges within the suggested network suppressed the toxic effects. We propose a novel structural aspect of Hsp100 chaperones crucial for specificity and efficiency of the disaggregation reaction.