Microduplication of Xp11.23p11.3 with effects on cognition,behavior, and craniofacial development

El‐Hattab AW, Bournat J, Eng PA, Wu JBS, Walker BA, Stankiewicz P, Cheung SW, Brown CW. Microduplication of Xp11.23p11.3 with effects on cognition, behavior, and craniofacial development. We report an ～1.3 Mb tandem duplication at Xp11.23p11.3 in an 11‐year‐old boy with pleasant personality, hyperactivity, learning and visual‐spatial difficulties, relative microcephaly, long face, stellate iris pattern, and periorbital fullness. This clinical presentation is milder and distinct from that of patients with partially overlapping Xp11.22p11.23 duplications which have been described in males and females with intellectual disability, language delay, autistic behaviors, and seizures. The duplicated region harbors three known X‐linked mental retardation genes: FTSJ1, ZNF81, and SYN1. Quantitative polymerase chain reaction from whole blood total RNA showed increased expression of three genes located in the duplicated region: EBP, WDR13, and ZNF81. Thus, over‐expression of genes in the interval may contribute to the observed phenotype. Many of the features seen in this patient are present in individuals with Williams‐Beuren syndrome (WBS). Interestingly, the SYN1 gene within the duplicated interval, as well as the STX1A gene, within the WBS critical region, co‐localize to presynaptic active zones, and play important roles in neurotransmitter release.     

Genome‐wide transcriptome analyses reveal p53 inactivation mediated loss of miR‐34a expression in malignant peripheral nerve sheath tumours

Malignant peripheral nerve sheath tumours (MPNSTs) are aggressive soft tissue tumours that occur either sporadically or in patients with neurofibromatosis type 1. The malignant transformation of the benign neurofibroma to MPNST is incompletely understood at the molecular level. We have determined the gene expression signature for benign and malignant PNSTs and found that the major trend in malignant transformation from neurofibroma to MPNST consists of the loss of expression of a large number of genes, rather than widespread increase in gene expression. Relatively few genes are expressed at higher levels in MPNSTs and these include genes involved in cell proliferation and genes implicated in tumour metastasis. In addition, a gene expression signature indicating p53 inactivation is seen in the majority of MPNSTs. Subsequent microRNA profiling of benign and malignant PNSTs indicated a relative down‐regulation of miR‐34a in most MPNSTs compared to neurofibromas. In vitro studies using the cell lines MPNST‐14 (NF1 mutant) and MPNST‐724 (from a non‐NF1 individual) show that exogenous expression of p53 or miR‐34a promotes apoptotic cell death. In addition, exogenous expression of p53 in MPNST cells induces miR‐34a and other miRNAs. Our data show that p53 inactivation and subsequent loss of expression of miR‐34a may significantly contribute to the MPNST development. Collectively, our findings suggest that deregulation of miRNAs has a potential role in the malignant transformation process in peripheral nerve sheath tumours. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Genetics of cardiovascular and renal complications in diabetes

The development of debilitating complications represents a major heathcare burden associated with the treatment of diabetes. Despite advances in new therapies for controlling hyperglycemia, the burden associated with diabetic complications remains high, especially in relation to cardiovascular and renal complications. Furthermore, an increasing proportion of patients develop type 2 diabetes at a younger age, putting them at higher risk of developing complications as a result of the increased exposure to hyperglycemia. Diabetes has become the main contributing cause to end‐stage renal disease in most countries. Although there has been important breakthroughs in our understanding of the genetics of type 1 and type 2 diabetes, bringing important insights towards the pathogenesis of diabetes, there has been comparatively less progress in our understanding of the genetic basis of diabetic complications. Genome‐wide association studies are beginning to expand our understanding of the genetic architecture relating to diabetic complications. Improved understanding of the genetic basis of diabetic cardiorenal complications might provide an opportunity for improved risk prediction, as well as the development of new therapies.     

Bamboo skewer perforation of the bowel: Computed tomography appearances

A 25-year-old Chinese woman presented with a painful left-lower-quadrant abdominal mass. Computed tomography (CT) demonstrated a dense forked foreign body within an extraluminal mass. A 2.5 cm bamboo skewer surrounded by inflamed omentum was found at laparotomy. Different CT densities of bamboo skewers were obtained when exposed to air, water and 2% Gastrografin in an in vitro experiment. Awareness of the possible variations in appearances of wooden foreign bodies in and around the bowel may aid their CT diagnoses.     

Three-compartment wrist arthrography: use of a low-iodine-concentration contrast agent to decrease study time

To decrease examination time, the authors used a contrast agent with a low iodine concentration for three-compartment (radiocarpal joint, distal radioulnar joint, midcarpal compartment) wrist arthrography. The material was used in 24 patients. Many patients demonstrated dissipation of contrast material in the radiocarpal joint by 30 minutes after injection. By 45 minutes, all patients demonstrated sufficient dissipation to permit the second injection. The technique produces diagnostic images and reduces the time required for the study.     

The contrasting influence of chronic nicotine intake on gastrin and gastric acid secretion

The effects of chronic nicotine treatment on gastric acid secretion stimulated by subcutaneous injection of pentagastrin, as well as on serum gastrin levels and the stomach parietal cell population, were examined. Rats drank a solution of nicotine 25 μg/mL tap water for periods of 10, 30 or 45 days. Pentagastrin increased the gastric secretory volume and acid output in pylorus-ligated control animals that drank tap water. Animals given nicotine in their drinking water for 10, 30 or 45 days showed increased basal gastric secretion and acid output. Pentagastrin produced maximum stimulatory effects at lower dose levels of 50 μg/kg in the 10-day treatment group and 25 μg/kg in the 30- or 45-day treatment groups; however, the maximum responses to pentagastrin in all nicotine-treated batches were comparable to those of their corresponding controls. Serum gastrin levels remained unchanged from the 10th day of nicotine treatment, whereas the levels in the control animals continued to rise with age. Nicotine 25 μg/mL drinking water given for 10, 30 or 45 days caused no significant changes in the parietal cell population, mucosal surface area or mucosal thickness. These findings are consistent with the idea that chronic nicotine administration, for at least 10 days, will lead to increased muscarinic receptor sensitivity; basal acid secretion is consequently elevated, and this in turn may depress gastrin secretion.     

Risky behavior in teens with cystic fibrosis or sickle cell disease: a multicenter study

OBJECTIVE: To determine the prevalence and age of onset of common risky behaviors such as smoking and sexual activity in teens with cystic fibrosis and those with sickle cell disease and to compare their behaviors with those of adolescents in the general population. DESIGN: Survey. SETTING: All five major pediatric tertiary care centers in North Carolina (study participants with sickle cell disease or cystic fibrosis) and North Carolina public schools (comparison population). PARTICIPANTS: Three hundred twenty-one adolescents with cystic fibrosis or sickle cell disease aged 12 to 19 years (mean age, 15.6 years; 49% female). Demographically matched comparison teens for each group were selected from 2760 in-school adolescents (mean age, 16.0 years; 51% female). MAIN OUTCOMES MEASURES: Prevalence of tobacco and marijuana use, alcohol use, sexual intercourse, sexually transmitted diseases, seat belt use, weapon carrying, and age of onset of these behaviors. RESULTS: Chronically ill teens reported significantly less lifetime and current use of tobacco, marijuana, and alcohol; less sexual intercourse; less weapon carrying, less drunk driving, and more seat belt use than their peers. Nonetheless, 21% of the teens with cystic fibrosis and 30% of those with sickle cell disease had smoked; sexual intercourse was reported by 28% and 51%, respectively. Age of onset of these behaviors was frequently older for the chronically ill teens. CONCLUSION: Teens with cystic fibrosis or sickle cell disease took more potentially damaging health risks than might be expected, although the prevalence was lower than reported by their peers. Future longitudinal studies should examine the relationships between chronic illness, physical and psychosocial maturation, and risky behavior. Screening for psychosocial issues, including risky behaviors, should be incorporated into the routine health care of chronically ill teens.     

Factors associated with the duration of breastfeeding amongst women in Perth, Australia

Duration of breastfeeding was studied in 556 women delivering at 2 maternity hospitals in Perth, Australia. At discharge 83.8% of women were breastfeeding their infants, including 6% who were giving complementary feeds. At 3 and 6 months, 61.8% and 49.9%, respectively, were still breastfeeding. In a Cox survival analysis of factors associated with duration of breastfeeding a positive association was found with maternal education, age and intended duration of breastfeeding. Male infants were more likely to be weaned before female infants and women whose partners were unemployed, or did not have a preference for breastfeeding, breastfed for shorter duration. There is still a need for programmes which support and encourage breastfeeding, focusing particularly on younger, less well-educated women who intend to breastfeed for less than the recommended 4-6 months.     

Oral chronic graft‐versus‐host disease: current pathogenesis,therapy, and research

Optimal management of complex autoimmune diseases requires a multidisciplinary medical team including dentists to care for lesions of the oral cavity. In this review, we discuss the presentation, prevalence, diagnosis, and treatment of oral manifestations in chronic graft‐versus‐host disease (cGVHD), which is a major late complication in patients treated by allogeneic hematopoietic stem cell transplantation. We assess current general knowledge of systemic and oral cGVHD and present general treatment recommendations based on literature review and our clinical experience. Additionally, we review areas where the understanding of oral cGVHD could be improved by further research and address tools with which to accomplish the long‐term goal of providing better health and quality of life to patients with cGVHD.