North African Influences and Potential Bias in Case-Control Association Studies in the Spanish Population

BACKGROUND: Despite the limited genetic heterogeneity of Spanish populations, substantial evidences support that historical African influences have not affected them uniformly. Accounting for such population differences might be essential to reduce spurious results in association studies of genetic factors with disease. Using ancestry informative markers (AIMs), we aimed to measure the African influences in Spanish populations and to explore whether these might introduce statistical bias in population-based association studies. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 93 AIMs in Spanish (from the Canary Islands and the Iberian Peninsula) and Northwest Africans, and conducted population and individual-based clustering analyses along with reference data from the HapMap, HGDP-CEPH, and other sources. We found significant differences for the Northwest African influence among Spanish populations from as low as ≈ 5% in Spanish from the Iberian Peninsula to as much as ≈ 17% in Canary Islanders, whereas the sub-Saharan African influence was negligible. Strikingly, the Northwest African ancestry showed a wide inter-individual variation in Canary Islanders ranging from 0% to 96%, reflecting the violent way the Islands were conquered and colonized by the Spanish in the XV century. As a consequence, a comparison of allele frequencies between Spanish samples from the Iberian Peninsula and the Canary Islands evidenced an excess of markers with significant differences. However, the inflation of p-values for the differences was adequately controlled by correcting for genetic ancestry estimates derived from a reduced number of AIMs. CONCLUSIONS/SIGNIFICANCE: Although the African influences estimated might be biased due to marker ascertainment, these results confirm that Northwest African genetic footprints are recognizable nowadays in the Spanish populations, particularly in Canary Islanders, and that the uneven African influences existing in these populations might increase the risk for false positives in association studies. Adjusting for population stratification assessed with a few dozen AIMs would be sufficient to control this effect

Antibiotic-loaded nanoparticles targeted to the site of infection enhance antibacterial efficacy

Bacterial resistance to antibiotics has made it necessary to resort to using antibacterial drugs that have considerable toxicities. Here, we show that conjugation of vancomycin-loaded nanoparticles with the cyclic 9-amino-acid peptide CARGGLKSC (CARG), identified via phage display on Staphylococcus aureus (S. aureus) bacteria and through in vivo screening in mice with S. aureusinduced lung infections, increases the antibacterial activity of the nanoparticles in S. aureus-infected tissues and reduces the systemic dose needed, minimizing side effects. CARG binds specifically to S. aureus bacteria but not Pseudomonas bacteria in vitro, selectively accumulates in S. aureus-infected lungs and skin of mice but not in non-infected tissue and Pseudomonas-infected tissue, and significantly enhances the accumulation of intravenously injected vancomycin-loaded porous silicon nanoparticles bearing CARG in S. aureus-infected mouse lung tissue. The targeted nanoparticles more effectively suppress staphylococcal infections in vivo relative to equivalent doses of untargeted vancomycin nanoparticles or of free vancomycin. The therapeutic delivery of antibiotic-carrying nanoparticles bearing peptides targeting infected tissues may help combat difficult-to-treat infections

Porous Silicon Particles for Cancer Therapy and Bioimaging

Porous silicon (pSi) engineered by electrochemical etching of silicon has been explored as a drug delivery carrier with the aim of overcoming the limitations of traditional therapies and medical treatments. pSi is biodegradable, non-cytotoxic and has optoelectronic properties that make this platform material a unique candidate for developing biomaterials for drug delivery and theranostics therapies. pSi provides new opportunities to improve existing therapies in different areas, paving the way for developing advanced theranostic nanomedicines, incorporating payloads of therapeutics with imaging capabilities. However, despite these outstanding advances, more extensive in-vivo studies are needed to assess the feasibility and reliability of this technology for real clinical practice. In this Chapter, we present an updated overview about the recent therapeutic systems based on pSi, with a critical analysis on the problems and opportunities that this technology faces as well as highlighting the growing potential of pSi technolgy