Insulin-dependent (type 1) diabetes is a prototypic organ-specific autoimmune disease resulting from the selective destruction of insulin-secreting beta cells within pancreatic islets of Langerhans by an immune-mediated inflammation involving autoreactive CD4(+) and CD8(+) T lymphocytes which infiltrate pancreatic islets. Current treatment is substitutive, i.e. chronic use of exogenous insulin which, in spite of significant advances, is still associated with major constraints (multiple daily injections, risks of hypoglycaemia) and lack of effectiveness over the long term in preventing severe degenerative complications. Finding a cure for autoimmune diabetes by establishing effective immune-based therapies is a real medical health challenge, as the disease incidence increases steadily in industrialized countries. As the disease affects mainly children and young adults, any candidate immune therapy must therefore be safe and avoid a sustained depression of immune responses with the attendant problems of recurrent infection and drug toxicity. Thus, inducing or restoring immune tolerance to target autoantigens, controlling the pathogenic response while preserving the host reactivity to exogenous/unrelated antigens, appears to be the ideal approach. Our objective is to review the major progress accomplished over the last 20 years towards that aim. In addition, we would like to present another interesting possibility to access new preventive strategies based on the 'hygiene hypothesis', which proposes a causal link between the increasing incidence of autoimmune diseases, including diabetes, and the decrease of the infectious burden. The underlying rationale is to identify microbial-derived compounds mediating the protective activity of infections which could be developed therapeutically.
Cites: J Immunol. 2000 Jun 1;164(11):5683-810820244
The first genome-wide association study for BMI identified a polymorphism, rs7566605, 10 kb upstream of the insulin-induced gene 2 (INSIG2) transcription start site, as the most significantly associated variant in children and adults. Subsequent studies, however, showed inconsistent association of this polymorphism with obesity traits. This polymorphism has been hypothesized to alter INSIG2 expression leading to inhibition of fatty acid and cholesterol synthesis. Hence, we investigated the association of the INSIG2 rs7566605 polymorphism with obesity- and lipid-related traits in Danish and Estonian children (930 boys and 1,073 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of pre- and early pubertal children. The association between the polymorphism and obesity traits was tested using additive and recessive models adjusted for age, age-group, gender, maturity and country. Interactions were tested by including the interaction terms in the model. Despite having sufficient power (98%) to detect the previously reported effect size for association with BMI, we did not find significant effects of rs7566605 on BMI (additive, P = 0.68; recessive, P = 0.24). Accordingly, the polymorphism was not associated with overweight (P = 0.87) or obesity (P = 0.34). We also did not find association with waist circumference (WC), sum of four skinfolds, or with total cholesterol, triglycerides, low-density lipoprotein, or high-density lipoprotein. There were no gender-specific (P = 0.55), age-group-specific (P = 0.63) or country-specific (P = 0.56) effects. There was also no evidence of interaction between genotype and physical activity (P = 0.95). Despite an adequately powered study, our findings suggest that rs7566605 is not associated with obesity-related traits and lipids in the EYHS.
Previous studies have suggested that a locus predisposing to specific reading disability (dyslexia) resides on chromosome 6p23-p21.3. We investigated 79 families having at least two siblings affected with phonological coding dyslexia, the most common form of reading disability (617 people genotyped, 294 affected), and we tested for linkage with the genetic markers reported to be linked to dyslexia in those studies. No evidence for linkage was found by LOD score analysis or affected-sib-pair methods. However, using the affected-pedigree-member (APM) method, we detected significant evidence for linkage and/or association with some markers when we used published allele frequencies with weighting of rarer alleles. APM results were not significant when we used marker allele frequencies estimated from parents. Furthermore, results were not significant with the more robust SIMIBD method using either published or parental marker frequencies. Finally, family-based association analysis using the AFBAC program showed no evidence for association with any marker. We conclude that the APM method should be used only with extreme caution, because it appears to have generated false-positive results. In summary, using a large data set with high power to detect linkage, we were unable to find evidence for linkage or association between phonological coding dyslexia and chromosome 6p markers.
Cites: Am J Hum Genet. 1997 Jan;60(1):27-398981944
Cites: Am J Hum Genet. 1996 Apr;58(4):892-58644756
Little is known about whether the accuracy of tools for assessment of sexual offender recidivism risk holds across ethnic minority offenders. I investigated the predictive validity across ethnicity for the RRASOR and the Static-99 actuarial risk assessment procedures in a national cohort of all adult male sex offenders released from prison in Sweden 1993-1997. Subjects ordered out of Sweden upon release from prison were excluded and remaining subjects (N = 1303) divided into three subgroups based on citizenship. Eighty-three percent of the subjects were of Nordic ethnicity, and non-Nordic citizens were either of non-Nordic European (n = 49, hereafter called European) or African Asian descent (n = 128). The two tools were equally accurate among Nordic and European sexual offenders for the prediction of any sexual and any violent nonsexual recidivism. In contrast, neither measure could differentiate African Asian sexual or violent recidivists from nonrecidivists. Compared to European offenders, AfricanAsian offenders had more often sexually victimized a nonrelative or stranger, had higher Static-99 scores, were younger, more often single, and more often homeless. The results require replication, but suggest that the promising predictive validity seen with some risk assessment tools may not generalize across offender ethnicity or migration status. More speculatively, different risk factors or causal chains might be involved in the development or persistence of offending among minority or immigrant sexual abusers.
A total of 1,729 children (2nd-9th grades) in South Africa, Iceland, Poland, Australia, the U.K., and the U.S.A. rated 20 events in terms of how upsetting they are. Save in Poland, the ratings were in close agreement (r, .85-.97), placing the loss of parent at the top and a new baby sibling at the bottom. In Poland, the baby's arrival led the list. Even so, what was seen as quite upsetting fell everywhere in the same two categories--experiences that threaten one's sense of security and those that occasion personal denigration and embarrassment.
To assess the prevalence of ADHD symptoms and their relationship to psychopathology in adolescents from the European North of Russia.
The prevalence of ADHD symptoms is assessed by teacher reports in 536 adolescents. Internalizing and externalizing problems are assessed by teacher ratings and student self-reports.
Prevalence of individual ADHD symptoms ranges between 3.3% and 35%. Only 8.9% of boys and 3.6% of girls have positive ratings on six items in either inattention or hyperactivity subtype. These adolescents fare significantly worse regarding externalizing but not internalizing problems. Compared to girls with ADHD, boys with ADHD report higher levels of violent and nonviolent delinquency and are described by teachers as having more conduct problems. Possible ADHD status is associated with depressive symptoms in boys but not in girls.
The estimates of ADHD prevalence rates obtained in this study are similar to those of other countries, suggesting the need for identification and treatment of the disorder. Evaluation of associated disruptive behavior disorders and depression, particularly in boys, is warranted.
The aim of this study was to reveal whether today's children and adolescents have lower aerobic capacity compared with earlier studies. Aerobic capacity may be defined as the highest amount of oxygen a subject is able to consume per unit of time. Peak oxygen uptake (VO2peak) is often used as a measure of aerobic capacity in children. VO2peak in 196 healthy children and adolescents of both sexes, aged 8-16 years, was measured on a graded treadmill test. The mean results of VO2peak (l.min-1) showed only small differences compared with previous studies in Scandinavia. There was, however, greater dispersion in the present study when the VO2peak-values were corrected for weight (ml.kg-1.min-1) than in the earlier studies. When compared to other countries in Europe, Norwegian subjects achieved higher values. The reason may be due to either genetic differences or to a higher level of physical activity among the Norwegian subjects.
Nasopharyngeal carcinoma is a disease with a remarkable racial and geographical distribution. In most parts of the world it is a rare condition and in only a handful of places does this low risk profile alter. These include the Southern Chinese, Eskimos and other Arctic natives, inhabitants of South-East Asia and also the populations of North Africa and Kuwait.
Multiple sclerosis (MS) most commonly affects individuals of Northern European descent who live in countries at high latitude. The relative contributions of ancestry, country of birth and residence as determinants of MS risk have been studied in adult MS, but have not been explored in the pediatric MS population. In this study, we compare the demographics of pediatric- and adult-onset MS patients cared for in Toronto, Ontario, Canada, a multicultural region. The country of birth, residence during childhood, and ancestry were compared for 44 children and 573 adults. Our results demonstrate that although both the pediatric and adult cohorts were essentially born and raised in the same region of Ontario, Canada, children with MS were more likely to report Caribbean, Asian or Middle Eastern ancestry, and were less likely to have European heritage compared with individuals with adult-onset MS. The difference in ancestry between the pediatric and adult MS cohorts can be explained by two hypotheses: (1) individuals raised in a region of high MS prevalence, but whose ancestors originate from regions in which MS is rare, have an earlier age of MS onset, and (2) the place of residence during childhood, irrespective of ancestry, determines lifetime MS risk -- a fact that will be reflected in a change in the demographics of the adult MS cohort in our region as Canadian-raised children of recent immigrants reach the typical age of adult-onset MS.