Strain-Specific Differences in the Genetic Control of Two Closely Related Mycobacteria

The host response to mycobacterial infection depends on host and pathogen genetic factors. Recent studies in human populations suggest a strain specific genetic control of tuberculosis. To test for mycobacterial-strain specific genetic control of susceptibility to infection under highly controlled experimental conditions, we performed a comparative genetic analysis using the A/J- and C57BL/6J-derived recombinant congenic (RC) mouse panel infected with the Russia and Pasteur strains of Mycobacterium bovis Bacille Calmette Guérin (BCG). Bacillary counts in the lung and spleen at weeks 1 and 6 post infection were used as a measure of susceptibility. By performing genome-wide linkage analyses of loci that impact on tissue-specific bacillary burden, we were able to show the importance of correcting for strain background effects in the RC panel. When linkage analysis was adjusted on strain background, we detected a single locus on chromosome 11 that impacted on pulmonary counts of BCG Russia but not Pasteur. The same locus also controlled the splenic counts of BCG Russia but not Pasteur. By contrast, a locus on chromosome 1 which was indistinguishable from Nramp1 impacted on splenic bacillary counts of both BCG Russia and Pasteur. Additionally, dependent upon BCG strain, tissue and time post infection, we detected 9 distinct loci associated with bacillary counts. Hence, the ensemble of genetic loci impacting on BCG infection revealed a highly dynamic picture of genetic control that reflected both the course of infection and the infecting strain. This high degree of adaptation of host genetics to strain-specific pathogenesis is expected to provide a suitable framework for the selection of specific host-mycobacteria combinations during co-evolution of mycobacteria with humans

Reference values of bone stiffness index and C-terminal telopeptide in healthy European children

BACKGROUND/OBJECTIVE: Quantitative ultrasound measurements and bone metabolic markers can help to monitor bone health and to detect impaired skeletal development. Population-based reference values for children may serve as a basis for preventive measures to reduce the risk of osteoporosis and osteoporotic fractures in later life. This is the first paper providing age-, sex-and height-specific reference values for bone stiffness index (SI) and serum carboxy-terminal cross-linking telopeptide of type I collagen (CTX) in healthy, apparently prepubertal children. SUBJECTS/METHODS: In the population-based IDEFICS baseline survey (2007-2008) and follow-up (2009-2010), 18 745 children from eight European countries were newly recruited. A total of 10 791 2-10.9-year-old and 1646 3-8.9-year-old healthy children provided data on SI of the right and left calcaneus and serum CTX, respectively. Furthermore, height and weight were measured. Percentile curves were calculated using the General Additive Model for Location Scale and Shape (GAMLSS) to model the distribution of SI and CTX depending on multiple covariates while accounting for dispersion, skewness, and the kurtosis of this distribution. RESULTS: SI was negatively associated with age and height in children aged 2-5 years, whereas a positive association was observed in children aged 6-10 years. The dip in SI occurred at older age for higher SI percentiles and was observed earlier in taller children than in smaller children. The CTX reference curves showed a linear-positive association with age and height. No major sex differences were observed for the SI and CTX reference values. CONCLUSION: These reference data lay the ground to evaluate bone growth and metabolism in prepubertal children in epidemiological and clinical settings. They may also inform clinical practice to monitor skeletal development and to assess adverse drug reactions during medical treatments

When public action undermines public health: A critical examination of antifluoridationist literature

Background: The addition of the chemical fluorine to the water supply, called water fluoridation, reduces dental caries by making teeth more resistant to demineralisation and more likely to remineralise when initially decayed. This process has been implemented in more than 30 countries around the world, is cost-effective and has been shown to be efficacious in preventing decay across a person's lifespan. However, attempts to expand this major public health achievement in line with Australia's National Oral Health Plan 2004–2013 are almost universally met with considerable resistance from opponents of water fluoridation, who engage in coordinated campaigns to portray water fluoridation as ineffective and highly dangerous. Discussion: Water fluoridation opponents employ multiple techniques to try and undermine the scientifically established effectiveness of water fluoridation. The materials they use are often based on Internet resources or published books that present a highly misleading picture of water fluoridation. These materials are used to sway public and political opinion to the detriment of public health. Despite an extensive body of literature, both studies and results within studies are often selectively reported, giving a biased portrayal of water fluoridation effectiveness. Positive findings are downplayed or trivialised and the population implications of these findings misinterpreted. Ecological comparisons are sometimes used to support spurious conclusions. Opponents of water fluoridation frequently repeat that water fluoridation is associated with adverse health effects and studies are selectively picked from the extensive literature to convey only claimed adverse findings related to water fluoridation. Techniques such as "the big lie" and innuendo are used to associate water fluoridation with health and environmental disasters, without factual support. Half-truths are presented, fallacious statements reiterated, and attempts are made to bamboozle the public with a large list of claims and quotes often with little scientific basis. Ultimately, attempts are made to discredit and slander scientists and various health organisations that support water fluoridation. Summary: Water fluoridation is an important public health initiative that has been found to be safe and effective. Nonetheless, the implementation of water fluoridation is still regularly interrupted by a relatively small group of individuals who use misinformation and rhetoric to induce doubts in the minds of the public and government officials. It is important that public health officials are aware of these tactics so that they can better counter their negative effectJason M Armfiel