Half a Century of Wilson & Jungner: Reflections on the Governance of Population Screening.

In their landmark report on the "Principles and Practice of Screening for Disease" (1968), Wilson and Jungner noted that the practice of screening is just as important for securing beneficial outcomes and avoiding harms as the formulation of principles. Many jurisdictions have since established various kinds of "screening governance organizations" to provide oversight of screening practice. Yet to date there has been relatively little reflection on the nature and organization of screening governance itself, or on how different governance arrangements affect the way screening is implemented and perceived and the balance of benefits and harms it delivers.

Gene expression profiles induced by Salmonella infection in resistant and susceptible mice.

Mouse models have been extensively used to investigate the mechanisms of salmonellosis. However, the role of the hosts' local intestinal responses during early stages of infection remain unclear. In this study, transcript array analysis was employed to investigate regulation of gene expression in the murine intestine following oral challenge with Salmonella enterica serovar Enteritidis.

Interleukin-9 polymorphism in infants with respiratory syncytial virus infection: an opposite effect in boys and girls.

The predominance of severe respiratory syncytial virus (RSV) bronchiolitis in boys compared to girls is well known, but its mechanism is not yet understood. This is the first study focusing on gender-specific genetic factors affecting the risk of severe RSV infection using a previously described cohort. We determined 347 single-nucleotide polymorphisms (SNPs) in 470 children hospitalized for RSV infection, their parents, and 1,008 random population controls.

Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes.

Prematurity is a risk factor for severe respiratory syncytial virus bronchiolitis. We show that genetic factors in innate immune genes (IFNA13, IFNAR2, STAT2, IL27, NFKBIA, C3, IL1RN, TLR5), in innate and adaptive immunity (IFNG), and in airway remodeling genes (ADAM33 and TGFBR1), affect disease susceptibility to a different extent in preterm children, born with underdeveloped lungs, than in term children.

Comparative gene expression profiling in two congenic mouse strains following Bordetella pertussis infection.

Background: Susceptibility to Bordetella pertussis infection varies widely. These differences can partly be explained by genetic host factors. HcB-28 mice are more resistant to B.

Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes.

Background: Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract infection in infants. Only a proportion of children infected with RSV require hospitalization. Because known risk factors for severe disease, such as premature birth, cannot fully explain differences in disease severity, genetic factors have been implicated.

Toll-like receptor 4 polymorphism associated with the response to whole-cell pertussis vaccination in children from the KOALA study.

We examined the association between haplotype tagging single-nucleotide polymorphisms in TLR4 and the pertussis toxin-specific immunoglobulin G response after whole-cell pertussis (wP) vaccination in 515 1-year-old children from the KOALA study. A lower titer was associated with the minor allele of rs2770150, supporting a role for Toll-like receptor 4 in the antibody response to wP vaccination.

Lung response to Bordetella pertussis infection in mice identified by gene-expression profiling.

Host genetics determines the course of Bordetella pertussis infection in mice. Previously, we found four loci, Tlr4 and three novel loci, designated Bps 1-3, that are involved in the control of B. pertussis infection.

Host transcription profiles upon primary respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract infection in children. Severe RSV disease is related to an inappropriate immune response to RSV resulting in enhanced lung pathology which is influenced by host genetic factors. To gain insight into the early pathways of the pathogenesis of and immune response to RSV infection, we determined the transcription profiles of lungs and lymph nodes on days 1 and 3 after infection of mice.

IL-13 genetic polymorphism identifies children with late wheezing after respiratory syncytial virus infection.

Background: The nature of wheezing after respiratory syncytial virus lower respiratory tract infection (RSV LRTI) is usually transient. However, some children will develop persistent or late wheezing.

Objective: We hypothesized that early and late postbronchiolitis wheezing are determined by distinct clinical, immunologic, and genetic variables.

Adipose gene expression response of lean and obese mice to short-term dietary restriction.

Overweight and obesity lead to higher morbidity risks, which are alleviated even by mild weight loss. To gain insight in the molecular effects of weight loss in adipose tissue, we analyzed the effects of short-term dietary restriction (DR) on mice fed a low-fat diet (lean mice) or a high-fat diet (obese mice). Female C57Bl6/J mice on both diets were on DR until an average body weight loss of 20%, which was achieved in 8 to 12 days depending on body weight at the start of DR.

Adipose gene expression patterns of weight gain suggest counteracting steroid hormone synthesis.

Objective: To identify early molecular changes in weight gain, using analysis of gene expression changes in adipose tissue of mice fed well-defined humanized (Western) high-fat and low-fat (control) diets during a short (3- to 5-week) time interval.

Research Methods And Procedures: An adipose-enriched cDNA microarray was constructed and used for the expression analyses of visceral adipose tissues of wildtype young adult C57BL/6J male mice on different diets.

Results: Mice on a high-fat diet had significantly higher body weight (at most, 9.

Combining the transmission disequilibrium test and case-control methodology using generalized logistic regression.

To study the role of genetic factors in the etiology, susceptibility, or severity of disease, several methods are available. In a transmission disequilibrium test, genotypes of cases are compared to those of their parents to explore whether a specific allele, or marker, at a locus of interest appears to be transmitted in excess of what is expected on the basis of Mendelian inheritance. Such apparent excess transmission indicates that cases are being selected for that allele, thereby providing evidence that this allele is a risk factor for disease.

Leptin responsiveness to energy restriction: genetic variation in the leptin receptor gene.

Serum leptin concentrations are an important afferent signal in energy balance homeostasis. It has been speculated that the leptin responsiveness to energy restriction is affected by the functionality of the leptin receptor. The purpose of this analysis was to explore the effect of polymorphisms in the LEPR gene on the acute decline in leptin after 4 days of 65% energy restriction.

Influence of promoter variants of interleukin-10, interleukin-9, and tumor necrosis factor-alpha genes on respiratory syncytial virus bronchiolitis.

Previously, we reported genetic associations between severe respiratory syncytial virus (RSV) bronchiolitis in infants and polymorphisms in the interleukin (IL)-4 and IL-4 receptor alpha (IL-4Ralpha) genes, providing evidence for involvement of T helper type 2 cytokines in the pathogenesis of RSV bronchiolitis. We expanded our studies to polymorphisms in genes encoding IL-9, IL-10, and tumor necrosis factor (TNF)-alpha, using both a transmission/disequilibrium test and a case-control approach. Children homozygous for the IL-10 -592C or -592A allele had a higher risk of hospitalization for RSV bronchiolitis than did heterozygous carriers (odds ratio [OR], 1.

Genetic variation in the leptin receptor gene, leptin, and weight gain in young Dutch adults.

Objective: To investigate the association between leptin levels, polymorphisms in the leptin receptor (LEPR) gene, and weight gain.

Research Methods And Procedures: From two large prospective cohorts in The Netherlands (n = 17,500), we compared the baseline leptin of 259 subjects who had gained an average of 12.6 kg (range 5.

Association of severe respiratory syncytial virus bronchiolitis with interleukin-4 and interleukin-4 receptor alpha polymorphisms.

The association of variants of genes encoding interleukin (IL)-4 and the IL-4 receptor alpha chain (IL-4Ralpha) with respiratory syncytial virus (RSV) bronchiolitis was examined in hospitalized infants. Polymorphisms in IL-4 (C-590T) and IL-4Ralpha (I50V and Q551R) were genotyped by restriction fragment-length polymorphism analysis. Control subjects included parents of the hospitalized children (for the transmission/disequilibrium test), and a random population sample (for the case-control study).