Genomic imprinting plays a fundamental role in cancer and some hereditary diseases, including Beckwith–Wiedemann syndrome (BWS), a disorder of prenatal overgrowth and predisposition to embryonal ...malignancies such as Wilms tumor. We have previously shown that the K
V
LQT1 gene on chromosomal band 11p15 is imprinted, with expression of the maternal allele, and that the maternal allele is disrupted in rare BWS patients with balanced germ-line chromosomal rearrangements. We now show that an antisense orientation transcript within K
V
LQT1, termed LIT1 (long QT intronic transcript 1) is expressed normally from the paternal allele, from which K
V
LQT1 transcription is silent, and that in the majority of patients with BWS, LIT1 is abnormally expressed from both the paternal and maternal alleles. Eight of sixteen informative BWS patients (50%) showed biallelic expression, i.e., loss of imprinting (LOI) of LIT1. Similarly, 21 of 36 (58%) BWS patients showed loss of maternal allele-specific methylation of a CpG island upstream of LIT1. Surprisingly, LOI of LIT1 was not linked to LOI of insulin-like growth factor II (IGF2), which was found in 2 of 10 (20%) BWS patients, even though LOI of IGF2 occurs frequently in Wilms and other tumors, and in some patients with BWS. Thus, LOI of LIT1 is the most common genetic alteration in BWS. We propose that 11p15 harbors two imprinted gene domains—a more centromeric domain including K
V
LQT1 and p57
KIP2
, alterations in which are more common in BWS, and a more telomeric domain including IGF2, alterations in which are more common in cancer.
Purpose
To identify variations in practices used by nurses for pediatric patients with sickle cell disease (SCD) receiving chronic blood transfusion therapy for strokes.
Data sources
Descriptive ...study of a convenience sample of 11 nurses who care for children with SCD from nine institutions completed a closed‐ended questionnaire consisting of 37 items. Responses reflected practice experience with a total of 189 transfused patients with SCD.
Conclusions
A wide range of nursing practices exists for blood transfusion therapy for children with SCD and strokes. Manual partial exchange transfusion (66%) was the most commonly used method for blood transfusion in children with strokes reported among the nurses surveyed. Simple transfusions and erythrocytapheresis account for 21% and 13% of the practices reported. Opportunities exist to establish evidence‐based nursing care guidelines to improve the care of children with strokes receiving blood transfusion therapy.
Implications for practice
A wide range of local standard care guidelines for blood transfusion therapy exists. The results of this survey indicate that partial manual exchange transfusion is the most commonly used method of chronic blood transfusion therapy in children with SCD and stroke despite the fact that the magnitude of benefit in comparison with simple transfusion has not been established. Factors such as peripheral venous access, compliance with current chelation regimen, and the presence of antibodies are important considerations in the choice of method.
Simpson Golabi Behmel Syndrome (SGBS) is an Xlinked overgrowth syndrome with coarse craniofacial features that include hypertelorism, epicanthal folds, macrostomia, macroglossia, and antiverted ...nares. Associated with this disorder are a number of developmental abnormalities involving the extremities, chest wall, and abdominal wall as well as a number of internal organs including renal dysplasia, and cardiac malformations. Children with SGBS are at increased risk of developing Wilms’ tumor, neuroblastoma, and may have greater frequency of hepatic cancer and testicular gonadoblastoma. The causative gene for SGBS is the
Glypican3
(
GPC3
) gene located at Xq26 that encodes a glycosylphosphatidylinositollinked cell surface heparan sulfate proteoglycan that modulates the function of a number of growth factors and morphogens in vivo.
Lung cancer association studies have yielded suggestive but not definitive results for a few genes: CYP1A1 (in Japanese), GSTM1 and CYP2D6. We focus on variability in studies of lung cancer and the ...CYP2D6 gene (debrisoquine metabolic phenotype) as an instructive case and we propose some sources for this heterogeneity. Beyond the general sources of bias in all field studies, three specific concerns are relevant. First, evidence that CYP2D6 is expressed in the brain. The metabolic phenotypes have distinct psychological profiles and therefore there is the potential to distort studies through selection bias. Second, among the lung cancer histologic types, adenocarcinoma likely does not share increased genetic susceptibility due to CYP2D6. Third, the degree of smoking is likely to be related to genetic susceptibility. Effect modification by smoking should be sought for any putative genetic marker for lung cancer. Progress in understanding genetic susceptibility is likely to depend on future well-designed studies that adjust for these and other sources of bias. We are currently reanalyzing the original data from the published studies in order to further explore these issues.
•Children aged 5-12 years old with sickle cell anemia (SCA) living in low- and high-income settings are at risk of being underweight.•Lower hemoglobin levels and older age are associated with being ...underweight in children with SCA, irrespective of the setting.
Previously, we demonstrated that older children with sickle cell anemia (SCA) living in a low-income setting are at increased risk of death if they are underweight (weight-for-age z-score <-1). We now conducted a cross-sectional study in both low- and high-income settings to determine the consistent biological risk factors for being underweight across both low- and high-income settings for children aged 5-12 years old with SCA. The children from low- and high-income settings were eligible participants for the Primary Prevention of Stroke in Children with Sickle Cell Disease in Nigeria (SPRING, n=928) and the Silent Cerebral Infarct (SIT, North America/Europe, n=1,093) trials, respectively. The median age in the SPRING and SIT cohorts was 8.1 (IQR 6.3-10.3) and 8.5 (6.8-10.6) years, respectively (p=<0.001), and approximately half were male (49.0% and 50.8%, respectively, p=0.434). A total of 87.9% (n=816) of participants in SPRING (low-income) met the study criteria for underweight (weight-for-age z-score <-1) and 22.7% (n=211) for severely underweight (weight-for-age z-score <-3), significantly higher than the SIT (high-income) cohort at 25.7% (n=281) underweight and 0.7% (n=8) severely underweight (p<0.001 for both comparisons). In the combined cohort, older age (OR 1.24, p<0.001, 95% CI 1.17-1.31) and lower hemoglobin level (OR 0.67, p<0.001, 95% CI 0.60-0.75) were associated with being underweight. Age and hemoglobin level remained statistically significant in separate models for the SPRING and SIT cohorts. Older age and lower hemoglobin levels in children aged 5-12 with SCA are associated with increased odds of being underweight in both low- and high-income settings.
We report results based on mid-infrared photometry of comet 103P/Hartley 2 taken during 2010 May 4-13 (when the comet was at a heliocentric distance of 2.3 AU, and an observer distance of 2.0 AU) by ...the Wide-field Infrared Survey Explorer. Photometry of the coma at 22 {mu}m and data from the University of Hawaii 2.2 m telescope obtained on 2010 May 22 provide constraints on the dust particle size distribution, d log n/d log m, yielding power-law slope values of alpha = -0.97 {+-} 0.10, steeper than that found for the inbound particle fluence during the Stardust encounter of comet 81P/Wild 2. The extracted nucleus signal at 12 {mu}m is consistent with a body of average spherical radius of 0.6 {+-} 0.2 km (one standard deviation), assuming a beaming parameter of 1.2. The 4.6 {mu}m band signal in excess of dust and nucleus reflected and thermal contributions may be attributed to carbon monoxide or carbon dioxide emission lines and provides limits and estimates of species production. Derived carbon dioxide coma production rates are 3.5({+-} 0.9) x 10{sup 24} molecules per second. Analyses of the trail signal present in the stacked image with an effective exposure time of 158.4 s yields optical-depth values near 9 x 10{sup -10} at a delta mean anomaly of 0.2 deg trailing the comet nucleus, in both 12 and 22 {mu}m bands. A minimum chi-squared analysis of the dust trail position yields a beta-parameter value of 1.0 x 10{sup -4}, consistent with a derived mean trail-grain diameter of 1.1/{rho} cm for grains of {rho} g cm{sup -3} density. This leads to a total detected trail mass of at least 4 x 10{sup 10} {rho} kg.
Silent cerebral infarctions have been shown to cause major morbidity in children with sickle cell disease, suggesting that silent infarctions are not as "silent" as once thought. The current ...definition of silent infarction includes signal changes on magnetic resonance imaging, the absence of overt abnormalities on neurologic examination, and no history of focal neurologic event. Using a decision tree algorithm, we identified a cognitive profile distinguishing children with (n=16) and without (n=49) silent infarctions. The best model combined learning slope from the California Verbal Learning Test-Children's Version and Block Design from the Wechsler Abbreviated Scale of Intelligence. Accuracy was 75%, with 75% sensitivity and 76% specificity. Administration of a brief cognitive battery may be the most feasible approach to screen for silent infarctions in children with sickle cell disease.
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