Characterisation of peripheral bone mineral density in youth at risk of secondary osteoporosis - a preliminary insight.

OBJECTIVES: To describe peripheral long bone material and structural differences in youth at risk of secondary osteoporosis across disease-specific profiles. METHODS: Upper- and lower limbs of children and adolescents were scanned at 4% distal and 66% mid-shaft sites using peripheral Quantitative Computed Tomography sub-categorised as (1) increased risk of secondary osteoporosis (neuromuscular disorders; chronic diseases; endocrine diseases; inborn errors of metabolism; iatrogenic conditions), (2) low motor competence and (3) non-affected controls. RESULTS: Children with disease-specific profiles showed a range of bone deficits compared to the control group with these predominantly indicated for neuromuscular disorders, chronic diseases and low motor competence. Deficits between upper arm and lower leg long bone parameters were different for disease-specific profiles compared to the control group. Endocortical radius, muscle area, and mid-cortical ring density were not significantly different for any disease-specific profile compared to the control group for any bone sites. CONCLUSIONS: Neuromuscular disorders, chronic diseases and low motor competence have a strong correlation to bone health for appendicular bone parameters in youth, suggesting a critical mechanical loading influence which may differ specific to disease profile. As mechanical loading effects are observed in regional bone analyses, targeted exercise interventions to improve bone strength should be implemented to examine if this is effective in reducing the risk of secondary osteoporosis in youth.

Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly.

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms.

Do skinfolds accurately assess changes in body fat in obese children and adolescents?

PURPOSE: Obesity is epidemic in Western societies, with rapid rates of increase in the young. Various methods exist for the assessment of body composition, but these have not been compared in obese children and adolescents. This study compared methods of body composition assessment in obese young people to determine whether changes in various measures of body composition as a result of exercise training were correlated. METHODS: Multiple anthropometric measures (weight, height, body mass index (BMI), skinfolds, waist and hip girths) and dual-energy x-ray absorptiometry (DEXA) were undertaken in 38 obese children and adolescents (12.7 +/- 2.1 yr) at baseline and following 8 wk of exercise training. RESULTS: At baseline, there were strong relationships (all P < 0.01) between DEXA total fat and weight (r = 0.83), BMI (r = 0.86), waist girth (r = 0.81), hip girth (r = 0.88), sum of six skinfolds (sum6, r = 0.79), and percent body fat (percent body fat) calculated using a four-skinfold equation (EQ4; r = 0.69). Similar relationships (all P < 0.001) existed between DEXA abdominal fat and weight (r = 0.79), waist girth (r = 0.83), hip girth (r = 0.69), and height (r = 0.71). Neither skinfold sums, nor percent body fat calculated from skinfold equations, were selected as independent predictors of DEXA total or abdominal fat by stepwise hierarchical linear regression. The reductions in DEXA total and abdominal fat following exercise were not predicted by changes in skinfolds or percent body fat calculated from skinfolds. CONCLUSION: These data suggest that body fat derived from skinfold measures is poorly predictive of abdominal and total fat derived from DEXA in obese children and adolescents. This finding highlights the limitations of skinfolds in obese subjects and questions the validity of their use to assess changes in body composition with interventions such as exercise training.

Scatter and transmission doses from several pediatric X-ray examinations in a nursery.

BACKGROUND: While several studies have investigated the dose from scattered radiation from X-ray procedures in a pediatric nursery, they examined scatter from chest procedures only, or the types of examination were not specified. OBJECTIVE: The aim of this study was to collect scatter and transmission data from several types of X-ray examinations. MATERIALS AND METHODS: Using a "newborn" anthropomorphic phantom and an ion chamber, a series of scatter and transmission dose measurements were performed using typical exposure factors for chest, chest and abdomen, skull, skeletal long bone and spine procedures. The phantom was inside a crib for all exposures. RESULTS: The maximum scatter dose measured at 1 m from the field center was about 0.05 micro Gy per exposure for lateral skulls. Transmission doses for lateral exams were around 0.1 micro Gy per exposure at 1 m from the isocenter. CONCLUSIONS: The study demonstrated that scatter dose to other patients in a neonatal unit is not significant, assuming the distance between adjacent cribs is in the order of 1 m. Transmission doses are also low provided the beam is fully intercepted by the cassette. For an average workload the dose received by imaging technologists would be small.