Individuals with Cornelia de Lange Syndrome (CdLS) display diverse developmental deficits, including slow growth, multiple limb and organ abnormalities, and intellectual disabilities. Severely-affected individuals most often have dominant loss-of-function mutations in the Nipped-B-Like (NIPBL) gene, and milder cases often have missense or in-frame deletion mutations in genes encoding subunits of the cohesin complex. Cohesin mediates sister chromatid cohesion to facilitate accurate chromosome segregation, and NIPBL is required for cohesin to bind to chromosomes. Individuals with CdLS, however, do not display overt cohesion or segregation defects. Rather, studies in human cells and model organisms indicate that modest decreases in NIPBL and cohesin activity alter the transcription of many genes that regulate growth and development. Sister chromatid cohesion factors, including the Nipped-B ortholog of NIPBL, are also critical for gene expression and development in Drosophila melanogaster. Here we describe how a modest reduction in Nipped-B activity alters growth and neurological function in Drosophila. These studies reveal that Nipped-B heterozygous mutant Drosophila show reduced growth, learning, and memory, and altered circadian rhythms. Importantly, the growth deficits are not caused by changes in systemic growth controls, but reductions in cell number and size attributable in part to reduced expression of myc (diminutive) and other growth control genes. The learning, memory and circadian deficits are accompanied by morphological abnormalities in brain structure. These studies confirm that Drosophila Nipped-B mutants provide a useful model for understanding CdLS, and provide new insights into the origins of birth defects.

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The use of all-terrain vehicles (ATVs) has become increasingly popular as an outdoor recreational activity among people living in the United States, particularly in areas such as the southeast. There are significant risks involved with riding ATVs, especially in the pediatric population, due to lack of training and experience. The purpose of this study was to evaluate the outcomes of pediatric patients involved in ATVassociated accidents. MethodsThis study is a retrospective review of 98 pediatric patients ages 15 years and younger involved in ATV accidents who were admitted to a pediatric hospital between January 2015 and December 2020. Outcomes, including types of injuries sustained, length of hospital stay, length of ICU stay, and injury severity score (ISS) were analyzed between age groups (0-5, 6-10, and 11-15). ResultsThe mean hospital stay across all age groups was 1.7 ± 1.9 days, mean ICU stay was 3.8 ± 4.0 days, and mean injury severity score (ISS) was 5.9 ±4.8. The 11-15-year-old age group had a significantly longer hospital stay and higher ISS scores compared to both of the younger age groups (0-5 and 6-10 years old). There was no difference in ICU days between the age groups. Orthopedic injuries were the most common type of injury, occurring in 55% of all patients, followed by head injuries in 29% of patients, and spinal fractures in 2% of patients. The most common orthopedic fracture in the 11-15-year-old group was tibia/fibula, while humerus fractures were the most common type of fracture in the 0-5 and 6-10 year age groups. Orthopedic procedures were required in 35% of all included patients. There was no statistically significant difference in types of injuries and types of fractures sustained between each group. Chest injuries, including pneumothorax, lung contusions, and rib fractures, occurred most often in the older age group 11-15 years (n=65). Those who experienced chest injuries had a higher ISS, although it was not statistically significant (p=0.06) compared to those who did not have chest injuries. There was no difference in hospital or ICU length of stay in patients with chest injuries. ConclusionsThe results of this study demonstrate the outcomes of pediatric patients admitted for ATV accidents at a rural Appalachian pediatric hospital and provide an overview of the most common injuries involved in this trauma mechanism. Pediatric patients aged 11-15 years of age involved in ATV accidents are at risk for longer hospital length of stay and higher ISS compared to younger age groups. Additionally, patients ages 11-15 were more susceptible to chest injuries following ATV accidents. The results of this study will be used to develop a standardized trauma protocol for the management of this specific trauma mechanism in the pediatric population based on common injury patterns among each age group.

leads to a more favorable prognosis for the breast cancer patient.Breast-conserving surgery for early cancer of the breast requires adjunct radiotherapy. Friedman2 concluded from studying pathological tissues from 100 women who received radiation therapy that carcinoma of the breast cannot be considered a radiosensitive tumor. Radiation therapy produces initial fibrosis, loss of elasticity, fat necrosis, telangiectasia, lymphopenia, and obliterative arteritis. Tissue damage due to irradiation is not reversible. Radiation therapy is known to adversely affect the immune system. Breast cancer has a long natural history. One should not com¬ pare mortality based on the first 5 years following treatment. Haybittle et al3 found that late mortality was significantly in¬ creased in patients treated with radiotherapy. The excess mor¬ tality was related to increased deaths from heart disease and other cancers.Breast reconstructive surgery followingmastectomy was not included in the basic benefit package. Plastic surgery makes the restoration of a woman's breast after mastectomy a reality. Breast reconstruction may also be desired following lumpectomy and radiation therapy. Breast reconstruction plays a role in physical as well as psychological rehabilitation after mastec¬ tomy. Following breast reconstruction, women obtain a satis¬ factory return to wholeness and femininity. I believe that breast reconstruction should be considered as the final step in the treat¬ ment program of the mastectomy patient. I strongly disagree with the authors' wanting to limit routine follow-up testing after primary treatment of early breast can¬ cer. A second primary cancer developed in the opposite breast in 16.4% of patients followed up over 30 years by Adair et al.4 Without close follow-up, a small treatable cancer in the opposite breast would be missed. For those patients treated with breastconserving operations, one must consider that 33% of breast cancers are multifocal.5 These patients are at high risk for local and regional recurrences and require frequent screening and close follow-up to detect early local and regional recurrences be¬ fore they develop distant metastatic disease.The diagnosis and treatment of breast cancer will be com¬ promised and undermined by cost-containment restraints of a basic benefit package. A sound physician-patient relation¬ ship must be preserved. Beneficial treatment must not be denied. Quality of care must not be compromised to satisfy financial considerations. The implementation of a basic ben¬ efit package for the treatment of early breast cancer would be tantamount to rationing of care. of screening and treatment for early breast cancer: development of a basic benefit package. JAMA. 1995;273:142-148. 2. Friedman N. The effects of irradiation on breast cancer and the breast. CA Cancer J Clin. 1988;38:368-371. 3. Haybittle J, Brinkley D, Houghton J, et al. Postoperative radiotherapy and late mortality: evidence from the cancer research campaign trial for early breast cancer. women 40 to 50 years ...