The ‘Variant Normal’ Electrocardiogram of the Professional Football Player

The ECGs of highly trained athletes reveal variants that may incorrectly be called abnormal.     

Plasmodium falciparum synthetic LbL microparticle vaccine elicits protective neutralizing antibody and parasite-specific cellular immune responses

Epitopes of the circumsporozoite (CS) protein of Plasmodium falciparum, the most pathogenic species of the malaria parasite, have been shown to elicit protective immunity in experimental animals and human volunteers. The mechanisms of immunity include parasite-neutralizing antibodies that can inhibit parasite motility in the skin at the site of infection and in the bloodstream during transit to the hepatocyte host cell and also block interaction with host cell receptors on hepatocytes. In addition, specific CD4+ and CD8+ cellular mechanisms target the intracellular hepatic forms, thus preventing release of erythrocytic stage parasites from the infected hepatocyte and the ensuing blood stage cycle responsible for clinical disease. An innovative method for producing particle vaccines, layer-by-layer (LbL) fabrication of polypeptide films on solid CaCO₃ cores, was used to produce synthetic malaria vaccines containing a tri-epitope CS peptide T1BT* comprising the antibody epitope of the CS repeat region (B) and two T-cell epitopes, the highly conserved T1 epitope and the universal epitope T*. Mice immunized with microparticles loaded with T1BT* peptide developed parasite-neutralizing antibodies and malaria-specific T-cell responses including cytotoxic effector T-cells. Protection from liver stage infection following challenge with live sporozoites from infected mosquitoes correlated with neutralizing antibody levels. Although some immunized mice with low or undetectable neutralizing antibodies were also protected, depletion of T-cells prior to challenge resulted in the majority of mice remaining resistant to challenge. In addition, mice immunized with microparticles bearing only T-cell epitopes were not protected, demonstrating that cellular immunity alone was not sufficient for protective immunity. Although the microparticles without adjuvant were immunogenic and protective, a simple modification with the lipopeptide TLR2 agonist Pam₃Cys increased the potency and efficacy of the LbL vaccine candidate. This study demonstrates the potential of LbL particles as promising malaria vaccine candidates using the T1BT* epitopes from the P. falciparum CS protein.     

Calcium and vitamin D supplementation and incident rheumatoid arthritis: the Women’s Health Initiative Calcium plus Vitamin D trial

To determine whether calcium plus vitamin D supplementation (CaD) affects incidence of rheumatoid arthritis (RA). Participants enrolled in the Women??s Health Initiative CaD trial (n?=?36,282) were randomized to 1,000?mg calcium carbonate plus 400?IU of vitamin D₃ daily or to placebo. Incident RA cases were identified via self-report and validated rheumatic medication use. Cox proportional hazards models were used to compare RA incidence in the treatment versus placebo groups. The analysis included 32,435 women without the history of RA, of which 163 incident RA cases were identified over an average of 5.1?years. No significant differences in demographics, total personal vitamin D intake [P?=?0.36], or solar irradiance [P?=?0.68] were seen between the groups. In intention-to-treat analyses, no differences were observed in RA incidence [HR 1.04, 95% CI 0.76, 1.41]. No significant modifying effects were seen for stratum of age, solar irradiance, or total vitamin D intake, overall or when adjusted for adherence. Significant effect modifications were seen between CaD and total vitamin D intake and CaD and solar irradiance that suggest increased RA incidence with high vitamin D exposure. CaD supplementation did not demonstrate a significant effect on RA incidence in postmenopausal women. Modifying effects between CaD and both solar irradiance and dietary vitamin D intake are suggestive that multiple high vitamin D exposures may increase RA incidence. Further research is needed to fully explore the benefits and possible adverse effects of vitamin D supplementation on RA.