Effect of Omacor on HRV parameters in patients with recent uncomplicated myocardial infarction – A randomized, parallel group, double-blind, placebo-controlled trial: study design [ISRCTN75358739]

Background

A large body of data derived from animal, epidemiological and clinical studies indicate that n-3 polyunsaturated fatty acids have a favourable effect on the prognosis of patients with cardiovascular disease in general, and on reducing sudden death in particular. Depressed heart rate variability (HRV), an indicator of impairment of the autonomic nervous system, has been shown to be a powerful predictor of subsequent mortality in patients surviving an acute myocardial infarction. A multitude of studies have demonstrated this strong association, suggesting that the imbalance in the sympathic/parasympathetic system may facilitate emergence of ventricular arrhythmias. Heart rate variability parameters will be assessed in the present study, with the primary objective of evaluating the possible superiority of Omacor (a highly refined, concentrated omega-3 fatty acid) versus placebo in improving HRV from baseline to endpoint in patients with recent uncomplicated myocardial infarction. Both groups will receive optimal conventional treatment. The study will also explore and quantify improvement in time domain HRV indices and will assess the safety of administering Omacor to optimally treated post-infarction patients (conventional treatment).

Methods

This multi-centre study will evaluate the effect of Omacor 1 g, o.d. on time-domain HRV parameters in comparison to placebo o.d. in patients with recent uncomplicated transmural myocardial infarction. Patients will be screened during the first few days after the acute event as appropriate for the patient's condition, and after obtaining informed consent. Based on inclusion/exclusion criteria, a first 24-hour Holter recording will be performed. Two to five days later, screened patients still eligible for the study will undergo a second 24-hour Holter recording. After the second Holter recording, all patients will be randomly allocated to treatment with Omacor 1 g, o.d. or placebo o.d. One hundred patients will be followed in double-blind fashion for a six-month period after randomization. Visits, including 24-hour Holter recording and assessment of adverse events, will take place at one-month intervals ± five days after randomization, i.e., six times in all.     

A re-evaluation of species limits in Chaetobromus (Danthonieae: Poaceae)

Past changes in the taxonomy of Chaetobromus , a Cape grass with considerable fodder potential, reflect a history of instability due to inadequate past sampling and intergradation among taxa in most characters. This biosystematic study differs from earlier investigations by its much more intensive approach to sampling, taking into consideration inter- and intrapopulational variation in 75 anatomical, morphological and cytological characters, across a total of 169 samples. Both phenetic methods and population aggregation analysis revealed the existence of three major groups, approximating three formerly described taxa and reflecting divergent ecological strategies in Chaetobromus . However, continuity among groups in most characters and a lack of clear-cut diagnostic field characters argues against their recognition at species level. Thus, Chaetobromus is here described as monotypic, the type species, C. involucratus , comprising three subspecies C. involucratus ssp. involucratus, C. involucratus ssp. sericeus and C. involucratus ssp. dregeanus .     

Probiotic strain <Emphasis Type="Italic">Bacillus subtilis</Emphasis> CU1 stimulates immune system of elderly during common infectious disease period: a randomized,double-blind placebo-controlled study

Background

Bacillus probiotics health benefits have been until now quite poorly studied in the elderly population. This study aimed to assess the effects of Bacillus subtilis CU1 consumption on immune stimulation and resistance to common infectious disease (CID) episodes in healthy free-living seniors.

Results

One hundred subjects aged 60–74 were included in this randomized, double-blind, placebo-controlled, parallel-arms study. Subjects consumed either the placebo or the probiotic (2.10⁹ B. subtilis CU1 spores daily) by short periodical courses of 10 days intermittently, alternating 18-day course of break. This scheme was repeated 4 times during the study. Symptoms of gastrointestinal and upper/lower respiratory tract infections were recorded daily by the subjects throughout the study (4 months). Blood, saliva and stool samples were collected in a predefined subset of the first forty-four subjects enrolled in the study. B. subtilis CU1 supplementation did not statistically significantly decrease the mean number of days of reported CID symptoms over the 4-month of study (probiotic group: 5.1 (7.0) d, placebo group: 6.6 (7.3) d, P?=?0.2015). However, in the subset of forty-four randomized subjects providing biological samples, we showed that consumption of B. subtilis CU1 significantly increased fecal and salivary secretory IgA concentrations compared to the placebo. A post-hoc analysis on this subset showed a decreased frequency of respiratory infections in the probiotc group compared to the placebo group.

Conclusion

Taken together, our study provides evidence that B. subtilis CU1 supplementation during the winter period may be a safe effective way to stimulate immune responses in elderly subjects.

     

Complex recombination patterns arising during geminivirus coinfections preserve and demarcate biologically important intra-genome interaction networks

Genetic recombination is an important process during the evolution of many virus species and occurs particularly frequently amongst begomoviruses in the single stranded DNA virus family, Geminiviridae. As in many other recombining viruses it is apparent that non-random recombination breakpoint distributions observable within begomovirus genomes sampled from nature are the product of variations both in basal recombination rates across genomes and in the over-all viability of different recombinant genomes. Whereas factors influencing basal recombination rates might include local degrees of sequence similarity between recombining genomes, nucleic acid secondary structures and genomic sensitivity to nuclease attack or breakage, the viability of recombinant genomes could be influenced by the degree to which their co-evolved protein-protein and protein-nucleotide and nucleotide-nucleotide interactions are disreputable by recombination. Here we investigate patterns of recombination that occur over 120 day long experimental infections of tomato plants with the begomoviruses Tomato yellow leaf curl virus and Tomato leaf curl Comoros virus. We show that patterns of sequence exchange between these viruses can be extraordinarily complex and present clear evidence that factors such as local degrees of sequence similarity but not genomic secondary structure strongly influence where recombination breakpoints occur. It is also apparent from our experiment that over-all patterns of recombination are strongly influenced by selection against individual recombinants displaying disrupted intra-genomic interactions such as those required for proper protein and nucleic acid folding. Crucially, we find that selection favoring the preservation of co-evolved longer-range protein-protein and protein DNA interactions is so strong that its imprint can even be used to identify the exact sequence tracts involved in these interactions.     

Prediction of time to exhaustion in competitive cyclists from a perceptually based scale

Prediction of time to exhaustion in competitive cyclists from a perceptually based scale. We have tested the validity of the estimated time limit (ETL) scale to predict an exhaustion time (T(lim)) from values stemming from incremental and randomized constant workloads tests on a cycle ergometer. Twenty-five cyclists performed 1 continuous incremental test, 1 discontinuous test with randomized workloads, and 1 constant power output test at 90% of maximal aerobic power (MAP) to exhaustion. Estimated time limits at 90% MAP during the incremental test and the test with randomized workloads were calculated from exponential relationships between power and ETL using the same 4 workloads. Real measured T(lim) during the constant power output test was converted into ETL values (called measured ETL). The differences between the calculated and measured ETLs were examined. Estimated time limits calculated at 90% MAP during the incremental and randomized tests corresponded to 14 minutes 56 seconds and 10 minutes 14 seconds, whereas measured ETL was equal to 11 minutes 19 seconds ± 3 minutes 40 seconds. The results showed a nonsignificant difference between calculated and measured ETLs. However, the mean differences between the measured ETL values during the constant test performed at the same intensity were -1.3 ± 2.9 and 0.3 ± 3.0 for the incremental and the randomized constant workloads tests, respectively. Consequently, the use of ETL calculated at 90% MAP during the test with randomized constant workloads may be preferable to predict the accurate T(lim). Moreover, it would seem that high-level cyclists, who were more consciously attuned to their bodies and their own effort sense, were more accurate in their prediction than low-level cyclists. It is concluded that the randomized constant workloads test that is both shorter and less strenuous would be more convenient for high-level athletes.     

The role of vascular actors in two dimensional dialogue of human bone marrow stromal cell and endothelial cell for inducing self-assembled network

Angiogenesis is very important for vascularized tissue engineering. In this study, we found that a two-dimensional co-culture of human bone marrow stromal cell (HBMSC) and human umbical vein endothelial cell (HUVEC) is able to stimulate the migration of co-cultured HUVEC and induce self-assembled network formation. During this process, expression of vascular endothelial growth factor (VEGF₁₆₅) was upregulated in co-cultured HBMSC. Meanwhile, VEGF₁₆₅-receptor2 (KDR) and urokinase-type plasminogen activator (uPA) were upregulated in co-cultured HUVEC. Functional studies show that neutralization of VEGF₁₆₅ blocked the migration and the rearrangement of the cells and downregulated the expression of uPA and its receptor. Blocking of vascular endothelial-cadherin (VE-cad) did not affect the migration of co-cultured HUVEC but suppressed the self-assembled network formation. In conclusion, co-cultures upregulated the expression of VEGF₁₆₅ in co-cultured HBMSC; VEGF₁₆₅ then activated uPA in co-cultured HUVEC, which might be responsible for initiating the migration and the self-assembled network formation with the participation of VE-cad. All of these results indicated that only the direct contact of HBMSC and HUVEC and their respective dialogue are sufficient to stimulate secretion of soluble factors and to activate molecules that are critical for self-assembled network formation which show a great application potential for vascularization in tissue engineering.     

Putting into practice domain-linear motif interaction predictions for exploration of protein networks

PDZ domains recognise short sequence motifs at the extreme C-termini of proteins. A model based on microarray data has been recently published for predicting the binding preferences of PDZ domains to five residue long C-terminal sequences. Here we investigated the potential of this predictor for discovering novel protein interactions that involve PDZ domains. When tested on real negative data assembled from published literature, the predictor displayed a high false positive rate (FPR). We predicted and experimentally validated interactions between four PDZ domains derived from the human proteins MAGI1 and SCRIB and 19 peptides derived from human and viral C-termini of proteins. Measured binding intensities did not correlate with prediction scores, and the high FPR of the predictor was confirmed. Results indicate that limitations of the predictor may arise from an incomplete model definition and improper training of the model. Taking into account these limitations, we identified several novel putative interactions between PDZ domains of MAGI1 and SCRIB and the C-termini of the proteins FZD4, ARHGAP6, NET1, TANC1, GLUT7, MARCH3, MAS, ABC1, DLL1, TMEM215 and CYSLTR2. These proteins are localised to the membrane or suggested to act close to it and are often involved in G protein signalling. Furthermore, we showed that, while extension of minimal interacting domains or peptides toward tandem constructs or longer peptides never suppressed their ability to interact, the measured affinities and inferred specificity patterns often changed significantly. This suggests that if protein fragments interact, the full length proteins are also likely to interact, albeit possibly with altered affinities and specificities. Therefore, predictors dealing with protein fragments are promising tools for discovering protein interaction networks but their application to predict binding preferences within networks may be limited.