CR1 Knops blood group alleles are not associated with severe malaria in the Gambia

The Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens Sl1/Sl2 and McC(a)/McC(b), we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with Sl:2 and McC(b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for Sl 2 (0.800, 1,365/1,706) and McC(b) (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McC(a) allele observed in all populations, the African Sl 2/McC(b) allele appears to have evolved as a result of positive selection (modified Nei-Gojobori test Ka-Ks/s.e.=1.77, P-value <0.05). Given the role of CR1 in host defense, our findings suggest that Sl 2 and McC(b) have arisen to confer a selective advantage against infectious disease that, in view of these case-control study data, was not solely Plasmodium falciparum malaria. Factors underlying the lack of association between Sl 2 and McC(b) with severe malaria may involve variation in CR1 expression levels

21-Hydroxylase Genotyping in Australasian Patients with Congenital Adrenal Hyperplasia

Mutations in CYP21 (21-hydroxylase) lead to congenital adrenal hyperplasia (CAH). We genotyped 26 probands with CAH by PCR-sequencing the entire CYP21 gene. 25/26 had homozygous or compound heterozygous mutations. The frequencies of mutations were similar to other populations with deletion/hybrid, 12 G splice and 1172N the most common. Five patients with a 1172N allele predicting simple-virilising CAH had a salt-wasting phenotype. Two other probands also had a more severe phenotype than predicted by genotype. Two families had both non-classic and salt-wasting phenotypes arising from combinations of three deleterious alleles. Two novel CYP21 alleles were detected: D106N and a large deletion encompassing CYP21 and adjacent pseudogene. Two rare CYP21 alleles were also found. Three of these four novel/rare alleles were only detected as a result of sequencing the entire CYP21 gene. Entire CYP21 sequencing will increase the number of mutations detected in CAH, and in combination with functional studies should contribute a greater understanding of phenotype-genotype correlations.

The infant feeding activity and nutrition trial (INFANT) an early intervention to prevent childhood obesity : cluster-randomised controlled trial

Background : Multiple factors combine to support a compelling case for interventions that target the development of obesity-promoting behaviours (poor diet, low physical activity and high sedentary behaviour) from their inception. These factors include the rapidly increasing prevalence of fatness throughout childhood, the instigation of obesity-promoting behaviours in infancy, and the tracking of these behaviours from childhood through to adolescence and adulthood. The Infant Feeding Activity and Nutrition Trial (INFANT) aims to determine the effectiveness of an early childhood obesity prevention intervention delivered to first-time parents. The intervention, conducted with parents over the infant\u27s first 18 months of life, will use existing social networks (first-time parent\u27s groups) and an anticipatory guidance framework focusing on parenting skills which support the development of positive diet and physical activity behaviours, and reduced sedentary behaviours in infancy.Methods/Design : This cluster-randomised controlled trial, with first-time parent groups as the unit of randomisation, will be conducted with a sample of 600 first-time parents and their newborn children who attend the first-time parents\u27 group at Maternal and Child Health Centres. Using a two-stage sampling process, local government areas in Victoria, Australia will be randomly selected at the first stage. At the second stage, a proportional sample of first-time parent groups within selected local government areas will be randomly selected and invited to participate. Informed consent will be obtained and groups will then be randomly allocated to the intervention or control group.Discussion : The early years hold promise as a time in which obesity prevention may be most effective. To our knowledge this will be the first randomised trial internationally to demonstrate whether an early health promotion program delivered to first-time parents in their existing social groups promotes healthy eating, physical activity and reduced sedentary behaviours. If proven to be effective, INFANT may protect children from the development of obesity and its associated social and economic costs.<br /

Genetic, household and spatial clustering of leprosy on an island in Indonesia: a population-based study

BACKGROUND: It is generally accepted that genetic factors play a role in susceptibility to both leprosy per se and leprosy type, but only few studies have tempted to quantify this. Estimating the contribution of genetic factors to clustering of leprosy within families is difficult since these persons often share the same environment. The first aim of this study was to test which correlation structure (genetic, household or spatial) gives the best explanation for the distribution of leprosy patients and seropositive persons and second to quantify the role of genetic factors in the occurrence of leprosy and seropositivity. METHODS: The three correlation structures were proposed for population data (n = 560), collected on a geographically isolated island highly endemic for leprosy, to explain the distribution of leprosy per se, leprosy type and persons harbouring Mycobacterium leprae-specific antibodies. Heritability estimates and risk ratios for siblings were calculated to quantify the genetic effect. Leprosy was clinically diagnosed and specific anti-M. leprae antibodies were measured using ELISA. RESULTS: For leprosy per se in the total population the genetic correlation structure fitted best. In the population with relative stable household status (persons under 21 years and above 39 years) all structures were significant. For multibacillary leprosy (MB) genetic factors seemed more important than for paucibacillary leprosy. Seropositivity could be explained best by the spatial model, but the genetic model was also significant. Heritability was 57% for leprosy per se and 31% for seropositivity. CONCLUSION: Genetic factors seem to play an important role in the clustering of patients with a more advanced form of leprosy, and they could explain more than half of the total phenotypic variance

Memory-experience gap in early adolescents' happiness reports

Studies among adult populations show that estimates of how happy one has felt in the past tend to be more positive than average happiness as assessed using time sampling techniques. This ‘memory-experience gap’ is attributed to cognitive biases, among which fading affect bias. In this paper we report a study among 352 pupils of a secondary school in the Netherlands. These youngsters reported subsequently: 1) how happy they had felt yesterday, 2) how happy they had felt during the last month, 3) what they had done the previous day and 4) how the

Relationships between exercise, smoking habit and mortality in more than 100,000 adults

This is the peer reviewed version of the following article: O'DONOVAN, G., HAMER, M. and STAMATAKIS, E., 2017. Relationships between exercise, smoking habit and mortality in more than 100,000 adults. International Journal of Cancer, 140(8), pp.1819-1827., which has been published in final form at http://dx.doi.org/10.1002/ijc.30611. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingExercise is associated with reduced risks of all-cause, cardiovascular disease (CVD), and cancer mortality; however, the benefits in smokers and ex-smokers are unclear. The aim of this study was to investigate associations between exercise, smoking habit and mortality. Self-reported exercise and smoking, and all-cause, CVD, and cancer mortality were assessed in 106,341 adults in the Health Survey for England and the Scottish Health Survey. There were 9149 deaths from all causes, 2839 from CVD, and 2634 from cancer during 999,948 person-years of follow-up. Greater amounts of exercise were associated with decreases and greater amounts of smoking were associated with increases in the risks of mortality from all causes, CVD and cancer. There was no statistically significant evidence of biological interaction; rather, the relative risks of all-cause mortality were additive. In the subgroup of 26,768 ex-smokers, the all-cause mortality hazard ratio was 0.70 (95% CI: 0.60, 0.80), the CVD mortality hazard ratio was 0.71 (0.55, 092), and the cancer mortality hazard ratio was 0.66 (0.52, 0.84) in those who exercised compared to those who did not. In the subgroup of 28,440 smokers, the all-cause mortality hazard ratio was 0.69 (0.57, 0.83), the CVD mortality hazard ratio was 0.66 (0.45, 0.96), and the cancer mortality hazard ratio was 0.69 (0.51, 0.94) in those who exercised compared to those who did not. Given that an outright ban is unlikely, this study is important because it suggests exercise reduces the risks of all-cause, CVD and cancer mortality by around 30% in smokers and ex-smokers

Sport, and use of anabolic androgenic steroids among Icelandic high school students: a critical test of three perspectives

<p>Abstract</p> <p>Background</p> <p>This study investigates the use of anabolic androgenic steroids (AAS) among a national representative sample of high school students in Iceland. We test several hypotheses drawn from three perspectives. The first perspective focuses on the use of AAS as an individual phenomenon motivated by the desire to succeed in sport. The second perspective views the use of AAS as shaped by norms and values embedded in social relationships of formally organized sport. The third perspective suggests that factors outside sport, which have been shown to correlate with the use of other substances, predict the use of AAS.</p> <p>Method</p> <p>We use logistic regression and predicted probabilities to analyze data from a national representative survey of 11031 Icelandic high school students.</p> <p>Results</p> <p>Our results indicated that the use of AAS is not significantly related to participation in formally organized sports. However, it positively relates to fitness and physical training in informal contexts. We found a relatively strong relationship between the use of AAS and the use of illicit substances and a moderate relationship between AAS use and alcohol and tobacco consumption. We also found a significant negative relationship between AAS use and school integration and school achievement, and a significant positive relationship between AAS use and school anomie. The relation between AAS use and family-related variables was weaker. Finally, we found that the relationship between sport participation, physical exercise, and AAS use varies across levels of anomie and integration.</p> <p>Conclusion</p> <p>Our findings suggest that the use of AAS and especially illegal substances should be considered more as a social and a health problem rather than a sport specific issue. We found that high school students participating in fitness and informal training outside of formally organized sport clubs are the main risk group and should be the target of prevention efforts. However, this should not be done at the expense of general risk factors that affect AAS and other substances used by the general population. Finally, we suggest that prevention efforts should target both groups and individuals.</p

IFNG +874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-γ production

<p>Abstract</p> <p>Background</p> <p>Interferon-gamma is a key cytokine in the protective responses against intracellular pathogens. A single nucleotide polymorphism (SNP) located in the first intron of the human IFN-γ gene can putatively influence the secretion of cytokine with an impact on infection outcome as demonstrated for tuberculosis and other complex diseases. Our aim was to investigate the putative association of IFNG+874T/A SNP with American tegumentary leishmaniasis (ATL) and also the influence of this SNP in the secretion of IFN-γ <it>in vitro</it>.</p> <p>Methods</p> <p>Brazilian ATL patients (78 cutaneous, CL, and 58 mucosal leishmaniasis, ML) and 609 healthy volunteers were evaluated. The genotype of +874 region in the IFN-γ gene was carried out by Amplification Refractory Mutational System (ARMS-PCR). <it>Leishmania</it>-induced IFN-γ production on peripheral blood mononuclear cell (PBMC) culture supernatants was assessed by ELISA.</p> <p>Results</p> <p>There are no differences between +874T/A SNP frequency in cases and controls or in ML versus CL patients. Cutaneous leishmaniasis cases exhibiting AA genotype produced lower levels of IFN-γ than TA/TT genotypes. In mucosal cases, high and low IFN-γ producers were clearly demonstrated but no differences in the cytokine production was observed among the IFNG +874T or A carriers.</p> <p>Conclusion</p> <p>Our results suggest that +874T/A polymorphism was not associated with either susceptibility or severity to leishmaniasis. Despite this, IFNG +874T/A SNP could be involved in the pathogenesis of leishmaniasis by influencing the amount of cytokine released by CL patients, although it could not prevent disease development. On the other hand, it is possible that in ML cases, other potential polymorphic regulatory genes such as TNF-α and IL-10 are also involved thus interfering with IFN-γ secretion.</p