Little is known about the pathogenesis of the phenotype in individuals with trisomy 21 mosaicism and Down syndrome. The primary goal of this study was to identify factors contributing to the observed phenotypic variation by evaluating 107 individuals having trisomy 21 mosaicism. To investigate a potential “threshold” effect due to trisomic imbalance, lymphocyte and buccal mucosa nuclei were scored using FISH. Overall, buccal cells showed a significantly higher frequency of trisomy than lymphocytes (P< 0.0001). Using latent class analysis, two phenotypic classes were identified based on the clinical findings of the propositi. Patients from class 1 had significantly fewer traits and a lower percentage of trisomic cells (mean of 37.3% lymphocytes; 34.5% buccal mucosa cells) when compared to those stratified into class 2 (54.0% lymphocytes; 53.4% buccal mucosa cells). Tissue-specific influences were also detected, with buccal mucosa trisomy levels being significantly correlated with IQ (P = 0.0094; both ectodermal derivatives), while congenital heart defects were significantly correlated with lymphocytes (P = 0.0286; both mesodermal embryonic derivatives). In conclusion, allowing for the distinction of two groups, we observed variation in phenotype, associated with the percentage of trisomic cells. We also observed tissue-specific effects on phenotype. The results of this study should enable geneticists and other health care professionals to provide information regarding optimal diagnostic approaches and anticipated clinical outcomes.
The clinical and cytogenetic findings associated with mosaicism for trisomy 21/Down syndrome are the focus of this review. The primary topics discussed in this overview of the extant literature include the history of this condition and its diagnosis, the incidence of mosaicism, the meiotic and/or mitotic chromosomal malsegregation events resulting in mosaicism, the observation of mosaicism in the parents of children with the non-mosaic form of Down syndrome, and the variation in phenotypic outcome for both constitutional and acquired traits present in people with mosaicism for trisomy 21/Down syndrome, including cognition, fertility, and overall phenotypic findings. Additional topics reviewed include the social conditions of people with mosaicism, as well as age-related and epigenetic alterations observed in people with mosaicism for trisomy 21/Down syndrome. .
Previous studies suggested Ataxia-telangiectasia group D complementing gene (ATDC) as an oncogene in many types of cancer. However, its expression and biological functions in non-small cell lung cancer (NSCLC) remain unclear. Herein, we investigated its expression pattern in 109 cases of human NSCLC samples by immunohistochemistry and found that ATDC was overexpressed in 62 of 109 NSCLC samples (56.88%). ATDC overexpression correlated with histological type (p<0.0001), tumor status (p = 0.0227) and histological differentiation (p = 0.0002). Next, we overexpressed ATDC in normal human bronchial epithelial cell line HBE and depleted its expression in NSCLC cell lines A549 and H1299. MTT and colony formation assay showed that ATDC overexpression promoted cell proliferation while its depletion inhibited cell growth. Furthermore, cell cycle analysis showed that ATDC overexpression decreased the percentage of cells in G1 phase and increased the percentage of cells in S phase, while ATDC siRNA treatment increased the G1 phase percentage and decreased the S phase percentage. Further study revealed that ATDC overexpression could up-regulate cyclin D1 and c-Myc expression in HBE cells while its depletion down-regulated cyclin D1 and c-Myc expression in A549 and H1299 cells. In addition, ATDC overexpression was also associated with an increased proliferation index, cyclin D1 and c-Myc expression in human NSCLC samples. Further experiments demonstrated that ATDC up-regulated cyclin D1 and c-Myc expression independent of wnt/β-catenin or p53 signaling pathway. Interestingly, ATDC overexpression increased NF-κB reporter luciferase activity and p-IκB protein level. Correspondingly, NF-κB inhibitor blocked the effect of ATDC on up-regulation of cyclin D1 and c-Myc. In conclusion, we demonstrated that ATDC could promote lung cancer proliferation through NF-κB induced up-regulation of cyclin D1 and c-Myc.
With changes in the Accreditation Council for Graduate Medical Education (ACGME) Common Program Requirements related to transitions in care effective July 1, 2011, sponsoring institutions and training programs must develop a common structure for transitions in care as well as comprehensive curricula to teach and evaluate patient handoffs. In response to these changes, within the Duke University Health System, the resident-led Graduate Medical Education Patient Safety and Quality Council performed a focused review of the handoffs literature and developed a plan for comprehensive handoff education and evaluation for residents and fellows at Duke. The authors present the results of their focused review, concentrating on the three areas of new ACGME expectations--structure, education, and evaluation--and describe how their findings informed the broader initiative to comprehensively address transitions in care managed by residents and fellows. The process of developing both institution-level and program-level initiatives is reviewed, including the development of an interdisciplinary minimal data set for handoff core content, training and education programs, and an evaluation strategy. The authors believe the final plan fully addresses both Duke's internal goals and the revised ACGME Common Program Requirements and may serve as a model for other institutions to comprehensively address transitions in care and to incorporate resident and fellow leadership into a broad, health-system-level quality improvement initiative.
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