AT1 receptor blockade for the prevention of cardiovascular events after myocardial infarction

Myocardial infarction is associated with high morbidity and mortality. Multiple therapeutic modalities have been shown to be effective in reducing adverse postmyocardial infarction outcomes. The most prominent drugs that have been used in this group of patients are those that oppose the effects of the renin-angiotensin-aldosterone system. These drugs include beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and aldosterone blockers. Following initial success with angiotensin-converting enzyme inhibitors in reducing mortality and cardiac remodeling in postmyocardial infarction patients, recent focus has been on adjunctive or alternative use of angiotensin II-receptor antagonists. Multiple large-scale, randomized trials have been conducted in order to compare angiotensin II-receptor antagonists with a combination of angiotensin II-receptor antagonists and angiotensin-converting enzyme inhibitors, and with angiotensin-converting enzyme inhibitors alone in postmyocardial infarction patients and also in heart failure. Although some results are conflicting, the weight of evidence is towards equivalency of these two groups of medicines, provided that the maximum effective dose of the angiotensin II-receptor antagonists is used. The combination of an angiotensin-converting enzyme inhibitor and an angiotensin II-receptor antagonist may have additional benefits for some, but not all, patients; for example, reducing morbidity and mortality in patients with chronic heart failure but not in postmyocardial infarction patients. Indeed, in the postmyocardial infarction setting, the combination appears simply to increase the side effects, without conferring additional benefits. Use of aldosterone antagonists as adjunctive therapy in postmyocardial infarction patients is associated with added benefits in terms of mortality reduction and will become the standard of care in this group of patients.     

Stroke in supplementary motor area mimicking functional disorder: a case report

Journal of Neurology - Supplementary motor area, the posterior third of the medial aspect of superior frontal gyrus, is known to be a heterogeneous area in function. It is involved in...     

Influences of history, geography, and religion on genetic structure: the Maronites in Lebanon

Cultural expansions, including of religions, frequently leave genetic traces of differentiation and in-migration. These expansions may be driven by complex doctrinal differentiation, together with major population migrations and gene flow. The aim of this study was to explore the genetic signature of the establishment of religious communities in a region where some of the most influential religions originated, using the Y chromosome as an informative male-lineage marker. A total of 3139 samples were analyzed, including 647 Lebanese and Iranian samples newly genotyped for 28 binary markers and 19 short tandem repeats on the non-recombinant segment of the Y chromosome. Genetic organization was identified by geography and religion across Lebanon in the context of surrounding populations important in the expansions of the major sects of Lebanon, including Italy, Turkey, the Balkans, Syria, and Iran by employing principal component analysis, multidimensional scaling, and AMOVA. Timing of population differentiations was estimated using BATWING, in comparison with dates of historical religious events to determine if these differentiations could be caused by religious conversion, or rather, whether religious conversion was facilitated within already differentiated populations. Our analysis shows that the great religions in Lebanon were adopted within already distinguishable communities. Once religious affiliations were established, subsequent genetic signatures of the older differentiations were reinforced. Post-establishment differentiations are most plausibly explained by migrations of peoples seeking refuge to avoid the turmoil of major historical events.     

Modulation of polycaprolactone composite properties through incorporation of mixed phosphate glass formulations

Phosphate-based glasses (PGs) and their composites are of interest as bone repair and tissue engineering scaffolds due to the totally degradable nature of the materials. This study has investigated the effect of Si and Fe on the properties of PG particulate-filled polycaprolactone (PCL) matrix composites. Two glass compositions were investigated (mol.%): 50P₂O₅, 40CaO and 10SiO₂ or Fe₂O₃ (Si₁₀ and Fe₁₀, respectively). All composites contained 40 vol.% particulate filler, either Si₁₀, Fe₁₀, or a blend (40Si₁₀/0Fe₁₀, 30Si₁₀/10Fe₁₀, 20Si₁₀/20Fe₁₀, 10Si₁₀/30Fe₁₀ or 0Si₁₀/40Fe₁₀). Ion release, weight loss and composite mechanical properties were characterised as a function of time in deionised water (DW) and phosphate-buffered saline (PBS), respectively. The potential for calcium phosphate deposition was assessed in simulated body fluid (SBF). Calcium and phosphate ion release in DW increased in tandem with the rate of composite weight loss, which increased with Si₁₀ content. A Si₁₀ content dependent rate of pH reduction was observed in DW. After 56 days the PG in the 40Si₁₀/0Fe₁₀ composite was completely dissolved, whereas 67% of that in the 0Si₁₀/40Fe₁₀ composite remained. The initial flexural strength of 40Si₁₀/0Fe₁₀ composites was significantly lower when compared with the other materials. An increase in Si₁₀ content led to an increase in Young’s modulus and a concomitant decrease in flexural strain. It was found that the PCL molecular weight (M_w) decreased dramatically with increasing Si₁₀ content. FTIR analysis showed that Si incorporation into PG led to reaction with the PCL ester bonds, resulting in a reduction in PCL M_w when processed at elevated temperatures. Changes in mechanical properties with time in PBS were glass blend dependent and a more rapid rate of reduction was observed in higher Si₁₀ content composites. After 28 days in SBF surface deposited brushite was formed in 20Si₁₀/20Fe₁₀ PG containing composites. Thus, the properties of PCL–PG composites could be tailored by controlling the phosphate glass blend composition.