A gene in the telomeric HLA complex distinct from HLA-A is involved in predisposition to juvenile idiopathic arthritis

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is associated with particular alleles at 3 different HLA loci: HLA-A, HLA-DR/DQ, and HLA-DP. These associations are independent of each other (i.e., they cannot be explained by the known linkage disequilibrium between alleles at these loci). The purpose of this study was to look for additional JIA susceptibility genes in the HLA complex. METHODS: One hundred two Norwegian JIA patients and 270 healthy individuals, all carrying the DQ4;DR8 haplotype, were investigated by scanning approximately 10 megabases of DNA covering the HLA complex with microsatellite polymorphisms. An expectation-maximization algorithm was used to estimate haplotype frequencies, and the distribution of microsatellite alleles on the high-risk DQ4;DR8 haplotype was compared between patients and controls, to exclude effects secondary to linkage disequilibrium with these susceptibility genes. RESULTS: Allele 5 at the microsatellite locus D6S265 (D6S265* 5), 100 kb centromeric of HLA-A, showed a strong positive association with the disease (odds ratio 4.7, corrected P < 10(-6)). Haplotype analysis demonstrated that the D6S265*5 association was not caused by linkage disequilibrium to the gene encoding HLA-A*02, which has previously been reported to be associated with JIA. Instead, our data suggested that a gene in linkage disequilibrium with D6S265*5, but distinct from HLA-A*02, is involved in the predisposition to JIA. CONCLUSION: We found that D6S265*5 could be a marker for an additional susceptibility gene in JIA which is distinct from A*02, adding to the risk conferred by DQ4;DR8.     

Physical fitness and physical activity in obese and nonobese Flemish youth

OBJECTIVE: To assess different aspects of physical fitness and physical activity in obese and nonobese Flemish youth. RESEARCH METHODS AND PROCEDURES: A random sample of 3214 Flemish schoolchildren was selected and divided into an "obese" and "nonobese" group based on body mass index and sum of skinfolds. Physical fitness was assessed by the European physical fitness test battery. Physical activity was estimated by a modified version of the Baecke Questionnaire. RESULTS: Obese subjects had inferior performances on all tests requiring propulsion or lifting of the body mass (standing-broad jump, sit-ups, bent-arm hang, speed shuttle run, and endurance shuttle run) compared with their nonobese counterparts (p < 0.001). In contrast, the obese subjects showed greater strength on handgrip (p < 0.001). Both groups had similar levels of leisure-time physical activity; however, nonobese boys had a higher sport index than their obese counterparts (p < 0.05). DISCUSSION: Results of this study show that obese subjects had poorer performances on weight-bearing tasks, but did not have lower scores on all fitness components. To encourage adherence to physical activity in obese youth, it is important that activities are tailored to their capabilities. Results suggest that weight-bearing activities should be limited at the start of an intervention with obese participants and alternative activities that rely more on static strength used.     

Criterion distances and correlates of active transportation to school in Belgian older adolescents

Background  

Since physical activity levels in older adolescents have the potential to be increased by stimulating active transportation to school (ATS), the most important correlates of ATS should be determined before developing interventions, especially in those adolescents for whom the distance to school is feasible for active commuting. The main aims of this study were to determine criterion distances for ATS in Belgian older adolescents, to examine multidimensional correlates of ATS in adolescents living within a feasible distance from school and to investigate the associations of ATS with total physical activity and with other physical activities besides ATS.     

Objectively measured physical activity, physical activity related personality and body mass index in 6- to 10-yr-old children: a cross-sectional study

Background  

The prevalence and level of overweight in childhood is rapidly increasing. One potential contributor to the rise in overweight is a decline in physical activity (PA). The purpose of this study was to compare levels and patterns of PA and PA related personality in normal-weight (NW) and overweight (OW) 6- to 10-yr-old children.     

Help,I’m losing patient‐centredness! Experiences of medical students and their teachers

Medical Education 2010: 44 : 662–673 Objectives Despite all educational efforts, the literature shows an ongoing decline in patient‐centredness during medical education. This study explores the experiences of medical students and their teachers and supervisors in relation to patient‐centredness in order to gain a better understanding of the factors that determine its development. Methods We conducted 11 focus groups on the subject of learning and teaching about patient‐centredness. We then carried out a constant comparative analysis of prior theory and the qualitative data collected in the focus groups using the ‘sensitising concepts’ provided by the Attitude–Social Influence–Self‐Efficacy (ASE) model. Results Although students express positive attitudes towards patient‐centredness and acquire patient‐centred skills during medical education, this study indicates that these are not sufficient to attain the level of competent behaviour needed in today’s challenging hospital environment. Clinical clerkships do provide students with ample opportunity to encounter patients and practise patient‐centred skills. However, when students lack self‐efficacy, when they face barriers (time pressure, tiredness) or when they are surrounded by non‐patient‐centred role models and are overwhelmed by powerful experiences, they lose their patient‐centred focus. The study suggests that communication skills training protects students from negative social influences. Moreover, personal development, including developing the ability to deal with emotions and personal suffering, self‐awareness and self‐care are important qualities of the central phenomenon of the ‘doctor‐as‐person’, which is identified as a missing concept in the ASE model. The student–supervisor relationship is found to be key to learning patient‐centredness and has several functions: it facilitates the direct transmission of patient‐centred skills, knowledge and attitudes; it provides social support of students’ patient‐centred behaviour; it provides support of the ‘student‐as‐person’; it mirrors patient‐centredness by being student‐centred, and, lastly, it addresses supervisor vulnerability. Finally, participants recommend that student‐centred education and guidance be offered, self‐awareness be fostered and more opportunities to encounter patients be created, including more time in general practice. Conclusions Supportive student–doctor relationships, student‐centred education and guidance that addresses the needs of the doctor‐as‐person are central to the development of patient‐centredness. Medical education requires patient‐centred, self‐caring and self‐aware role models.     

Spinal epidural hematomas

During the period 1943–1985 six patients were operated for spinal epidural hematomas at the department of neurosurgery of the University Hospital of Århus. It is essential to perform acute laminectomy in case of rapidly increasing neurological symptoms. In the case of slowly increasing symptoms operation may provide a good result even if it is performed a week after the onset of symptoms. It is important to watch patients with fracture/dislocations of the spine closely during the first weeks after a trauma. If they develop neurological symptoms the patients should immediately be transferred to the department of neurosurgery with a view of acute diagnosis and possibly acute surgery.     

Clinical validation of saquinavir/ritonavir genotypic resistance score in protease-inhibitor-experienced patients

OBJECTIVE: To identify a genotypic score for resistance to saquinavir boosted with ritonavir (SQV/r; 1,000/100 mg twice daily)-based regimens in protease inhibitor (PI)-experienced patients. METHODS: One-hundred and fifty-one PI-experienced patients receiving a SOV/r-containing regimen were enrolled retrospectively. The virological response (VR) was defined as the decrease in HIV RNA at months 3-5. The effect of each mutation in the protease gene on the VR to SQV/r regimen was assessed using non-parametric univariate analyses and then a step-by-step analysis was carried out using a Jonckheere-Tepstra (JT) nonparametric test to retain the group of mutations most strongly associated with VR. RESULTS: Among the 138 patients with detectable plasma SQV, the median VR was -1.48 [range: -4 to +1.2] log10 copies/ml. Changes at 12 codons were associated with a reduced VR to SQV/r: codons 10, 15, 20, 24, 46, 54, 62, 71, 73, 82, 84 and 90. The JT procedure led to selection of the following genotypic score, 10+15+20+ 24+62+73+82+84+90, as providing the strongest association with VR. In the 35 patients with none of the mutations in this score, the median decrease in HIV RNA was -2.24 log10 copies/ml and it was -1.88 (n=29), -1.43 (n=24), -0.52 (n=30), -0.18 (n=9), -0.11 (n=6) and -0.30 (n=5) log10 copies/ml in those with 1, 2, 3, 4, 5 and 6 mutations, respectively. CONCLUSION: With this resistance score to SQV/r, the isolates were classified as having no evidence of resistance (0-2), possible resistance (3) or resistance (> or =4) by grouping the number of mutations in samples for which the viral load reduction was similar.