Molecular insights into an ancient form of Paget's disease of bone.

Paget's disease of bone (PDB) is a chronic skeletal disorder that can affect one or several bones in individuals older than 55 y of age. PDB-like changes have been reported in archaeological remains as old as Roman, although accurate diagnosis and natural history of the disease is lacking. Six skeletons from a collection of 130 excavated at Norton Priory in the North West of England, which dates to medieval times, show atypical and extensive pathological changes resembling contemporary PDB affecting as many as 75% of individual skeletons. Disease prevalence in the remaining collection is high, at least 16% of adults, with age at death estimations as low as 35 y. Despite these atypical features, paleoproteomic analysis identified sequestosome 1 (SQSTM1) or p62, a protein central to the pathological milieu of PDB, as one of the few noncollagenous human sequences preserved in skeletal samples. Targeted proteomic analysis detected >60% of the ancient p62 primary sequence, with Western blotting indicating p62 abnormalities, including in dentition. Direct sequencing of ancient DNA excluded contemporary PDB-associated SQSTM1 mutations. Our observations indicate that the ancient p62 protein is likely modified within its C-terminal ubiquitin-associated domain. Ancient miRNAs were remarkably preserved in an osteosarcoma from a skeleton with extensive disease, with miR-16 expression consistent with that reported in contemporary PDB-associated bone tumors. Our work displays the use of proteomics to inform diagnosis of ancient diseases such as atypical PDB, which has unusual features presumably potentiated by yet-unidentified environmental or genetic factors.

The effectiveness of an indoor intermittent training program for improving lung function, physical capacity, body composition and quality of life in children with asthma.

OBJECTIVE: The objective of this study is to analyze the effects of a 12-week indoor intermittent training program on lung function, physical capacity, body composition and quality of life in children with asthma. METHODS: Participants were randomized in an experimental group (EG, 58 children, age = 11.55 ± 1.01 years) and in a control group (CG, 47 children, age = 11.51 ± 1.42 years). The training program was conducted indoors and consisted of alternating high- and low-intensity stimuli, for three sessions of 60 min/week, for 12 weeks. Physical exercise and sports activities were organized to follow the criteria of the American College of Sports Medicine (1999) and previous interventions' studies. RESULTS: In EG, there was a significant improvement (p < 0.05) in FEV1, FEV6, 6MWT, handgrip strength, CMJ and flexibility. Reductions in BMI and fat mass as well as an increase in quality of life were all shown. The dyspnea index decreased significantly and there were no episodes of EIA. There is a significant positive correlation (p < 0.01) between the ΔFEV1 with Δhandgrip strength and Δ6MWT and a negative correlation with Δfat mass. CONCLUSIONS: An indoor intermittent training program with these characteristics has improved lung function, physical capacity, body composition and quality of life in children with asthma. These training adaptations are particularly relevant for those patients suffering from asthma as a regular physical exercise routine will greatly improve their quality of life.

Validity and reliability of Physical Activity Enjoyment Scale questionnaire (PACES) in children with asthma.

OBJECTIVE: The aim of this study is to test the psychometric properties of the Physical Activity Enjoyment Scale (PACES) in children with asthma. METHOD: Participants included 185 children (age = 11.38 ± 1.12 years; body mass index = 20.66 ± 4.13 kg/m(2)): 107 children with asthma and 78 healthy children. To test the enjoyment of physical activity, PACES of Motl et al. was used in its Spanish version. In addition, the Physical Activity Questionnaire for Children (PAQ-C), Paediatric Asthma Quality of Life Questionnaire (PAQLQ) and Physical Self-Concept Questionnaire (CAF) have been used. RESULTS: The results have shown a two-factor structure corresponding to the model whose settings have been good. PACES internal consistency was very high (Cronbach's alpha = 0.906). The PACES test-retest reliability indicates a good temporal concordance (Spearman rho = 0.868, p < 0.001). This presents an adequate concurrent validity with the total PAQLQ, the PAQ-C as well as with ability, fitness, attractiveness, strength and general physical self-concept. CONCLUSIONS: The findings confirm that PACES is a valid and reliable measure of physical activity enjoyment in children with asthma.

Handgrip strength test as a complementary tool in monitoring asthma in daily clinical practice in children.

The aim of this study was to demonstrate that handgrip strength test can discriminate the presence/absence of asthma and between intermittent and moderate persistent asthma in children. 140 children (70 healthy and 70 with asthma) completed the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and performed the handgrip strength test. Forty-eight hours later, subjects performed spirometry. The results showed Handgrip strength was significantly lower (p<0.001) in children with asthma compared with healthy ones. There were also significant differences (p= 0.024) according to the severity of the disease; children with moderate persistent asthma performed worse than children with intermittent asthma. Binary logistic regression analysis and ROC curve analysis revealed that the result in handgrip strength test was a predictive factor for asthma (cut-off at 16.84 kg) and for severity of pathology (cut-off at 15.06 kg). Handgrip strength was reduced in children with asthma. Handgrip strength was positively associated with lung capacity and quality of life. The fact that the handgrip strength test was able to discriminate between presence/absence of asthma and between intermittent and moderate persistent asthma in children suggested that this test could be used as a complementary tool in the monitoring of asthma in daily clinical practice.