Early childhood factors influencing health-related quality of life in adolescents at 13 years

Early childhood factors influencing health-related quality of life in adolescents at 13 years . Wilkins , A.J. , O'Callaghan , M.J. , Najman , J.M. , Williams , G.M. & Shuttlewood , G. ( 2004 ) Journal of Paediatrics and Child Health 40 , 102 – 109 .     

Health-related quality of life of severely obese children and adolescents

Context One in seven US children and adolescents is obese, yet little is known about their health‐related quality of life (QOL). Objective To examine the health‐related QOL of obese children and adolescents compared with children and adolescents who are healthy or those diagnosed as having cancer. Design, setting and participants Cross‐sectional study of 106 children and adolescents (57 males) between the ages of 5 and 18 years [mean (SD) 12.1 (3) years], who had been referred to an academic children's hospital for evaluation of obesity between January and June 2002. Children and adolescents had a mean (SD) body mass index (BMI) of 34.7 (9.3) and BMI z‐score of 2.6 (0.5). Main outcome measures Child self‐report and parent‐proxy report using a paediatric QOL inventory generic core scale (range 0–100). The inventory was administered by an interviewer for children aged 5 through 7 years. Scores were compared with previously published scores for healthy children and adolescents and children and adolescents diagnosed as having cancer. Results Compared with healthy children and adolescents, obese children and adolescents reported significantly (P < 0.001) lower health‐related QOL in all domains [mean (SD) total score, 67 (16.3) for obese children and adolescents; 83 (14.8) for healthy children and adolescents]. Obese children and adolescents were more likely to have impaired health‐related QOL than healthy children and adolescents [odds ratio (OR) 5.5; 95% confidence interval (CI) 3.4–8.7] and were similar to children and adolescents diagnosed as having cancer (OR 1.3; 95% CI 0.8–2.3). Children and adolescents with obstructive sleep apnoea reported a significantly lower health‐related QOL total score [mean (SD), 53.8 (13.3)] than obese children and adolescents without obstructive sleep apnoea [mean (SD), 67.9 (16.2)]. For parent‐proxy report, the child or adolescent's BMI z‐score was significantly inversely correlated with total score (r = ?0.246; P = 0.01), physical functioning (r = ?0.263; P < 0.01), social functioning (r = ?0.347; P < 0.001), and psychosocial functioning (r = ?0.209; P = 0.03). Conclusions Severely obese children and adolescents have lower health‐related QOL than children and adolescents who are healthy and similar QOL as those diagnosed as having cancer. Physicians, parents and teachers need to be informed of the risk for impaired health‐related QOL among obese children and adolescents to target interventions that could enhance health outcomes.     

Enhanced chondrogenesis and Wnt signaling in PTH-treated fractures.

Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. INTRODUCTION: Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. MATERIALS AND METHODS: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. RESULTS: Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized beta-catenin protein, a central feature of canonical Wnt signaling. CONCLUSIONS: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways.     

Human Lyme arthritis and the immunoglobulin G antibody response to the 37-kilodalton arthritis-related protein of Borrelia burgdorferi

In Borrelia burgdorferi-infected C3H-scid mice, antiserum to a differentially expressed, 37-kDa spirochetal outer-surface protein, termed arthritis-related protein (Arp), has been shown to prevent or reduce the severity of arthritis. In this study, we determined the immunoglobulin G (IgG) antibody responses to this spirochetal protein in single serum samples from 124 antibiotic-treated human patients with early or late manifestations of Lyme disease and in serial serum samples from 20 historic, untreated patients who were followed longitudinally from early infection through the period of arthritis. These 20 patients were representative of the spectrum of the severity and duration of Lyme arthritis. Among the 124 antibiotic-treated patients, 53% with culture-proven erythema migrans (EM) had IgG responses to recombinant glutathione S-transferase (GST)-Arp, as did 59% of the patients with facial palsy and 68% of those with Lyme arthritis. In addition, 75 to 80% of the 20 past, untreated patients had reactivity with this protein when EM was present, during initial episodes of joint pain, or during the maximal period of arthritis. There was no association at any of these three time points between GST-Arp antibody levels and the severity of the maximal attack of arthritis or the total duration of arthritis. Thus, after the first several weeks of infection, 60 to 80% of patients had IgG antibody responses to GST-Arp, but this response did not correlate with the severity or duration of Lyme arthritis.     

Two large French pedigrees with non syndromic sensorineural deafness and the mitochondrial DNA T7511C mutation: evidence for a modulatory factor

Hearing impairment is the most frequent sensory defect in children, with a genetic basis in about 50% of cases. Several point mutations and deletions in mitochondrial DNA (mtDNA) have been identified in non-syndromic sensorineural hearing loss (NSSNHL). Beside the frequent A1555G mutation, a number of mutations in tRNAs have been reported recently, but their incidence remains unknown. We identified the T7511C mutation in the tRNASer(UCN) gene in two French families with isolated deafness. Maternal transmission was obvious in both. The 15 patients with hearing impairment exhibited a variable disease phenotype in terms of onset, severity, and progression. T7511C was present in all the patients screened. Homoplasmic and heteroplasmic levels were observed and did not correlate with the severity of the disease. T7511C was also present in 12 hearing offspring of the oldest deaf mothers, confirming the existence of modulatory factors. Our data suggest that this mtDNA mutation should be screened for in all cases of familial NSSNHL compatible with maternal transmission.     

Force enhancement by PEG during ramp stretches of skeletal muscle

We have investigated the effects of a stronger actomyosin bond on force (Ps) during rapid stretch of active permeabilized rabbit psoas muscle fibers as a function of temperature from 5 to 30 degrees C. The strength of the actomyosin bond is enhanced by addition of polyethylene glycol (PEG), especially in pre-powerstroke states [Chinn et al. (2000) Biophys J 49: 437-451]. We have hypothesized that such states produce much of the force when activated muscles are stretched [Getz et al. (1998) Biophys J 75: 2971-2983]. Addition of PEG to activated fibers produced a small increase in isometric tension, Po (50-90 kN/m2), which was approximately independent of temperature. In contrast PEG produced a dramatic increase in Ps at low temperatures (200-300 kN/m2), but a modest increase at higher temperatures (70-90 kN/m2). We also measured Ps and Po in solutions containing the phosphate analog aluminum fluoride (AlF4) with and without PEG. In the absence of PEG, AlF4 reduced Po much more than Ps. Addition of PEG did not enhance Po, but enhanced Ps significantly. The contrasting effects of PEG on Ps and Po, and the effect of temperature can be explained by a model in which stretch force is produced by pre-powerstroke cross-bridges whose maximum distension is increased by PEG, and isometric force is produced by strongly bound cross-bridges whose bond strength is also enhanced by PEG, but to a lesser extent.     

Neutral Polymeric Surfactants Derived from Dextran: A Study of Their Aqueous Solution Behavior

Summary: Amphiphilic polysaccharides are obtained by hydrophobic modification of a neutral bacterial polysaccharide, dextran. By reacting the polysaccharide with aliphatic epoxides (epoxyoctane and epoxydodecane) in dimethyl sulfoxide, a series of amphiphilic polymers is obtained which covers a large range of structural parameters (length of the polysaccharide, number and nature of hydrocarbon moieties). The solution behavior of dextran derivatives is first characterized by viscometric measurements in dilute and semi‐dilute domains. The effects of molecular parameters on polymer viscosity behavior are evidenced and discussed. Information on the state of aggregation of polymers is obtained by the use of static and dynamic light scattering. The presence of aggregates in the dilute domain is clearly evidenced and their structural characteristics are estimated (size, molecular weight and number of aggregation). The aggregates are shown to account for the viscometric results in the examined concentration range, relating their chemical parameters (hydrodynamic radius and molecular weight) to the macroscopic behavior of the solutions.