Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia

We performed a meta-analysis of 3 genome-wide association studies to identify additional common variants influencing chronic lymphocytic leukemia (CLL) risk. The discovery phase was composed of genome-wide association study data from 1121 cases and 3745 controls. Replication analysis was performed in 861 cases and 2033 controls. We identified a novel CLL risk locus at 6p21.33 (rs210142; intronic to the BAK1 gene, BCL2 antagonist killer 1; P = 9.47 × 10(-16)). A strong relationship between risk genotype and reduced BAK1 expression was shown in lymphoblastoid cell lines. This finding provides additional support for polygenic inheritance to CLL and provides further insight into the biologic basis of disease development.     

Mimicking the tumour microenvironment: three different co-culture systems induce a similar phenotype but distinct proliferative signals in primary chronic lymphocytic leukaemia cells

Interactions in the tumour microenvironment can promote chronic lymphocytic leukaemia (CLL) cell survival, proliferation and drug resistance. A detailed comparison of three co-culture systems designed to mimic the CLL lymph node and vascular microenvironments were performed; two were mouse fibroblast cell lines transfected with human CD40LG or CD31 and the third was a human microvascular endothelial cell line, HMEC-1. All three co-culture systems markedly enhanced CLL cell survival and induced a consistent change in CLL cell phenotype, characterized by increased expression of CD38, CD69, CD44 and ITGA4 (CD49d); this phenotype was absent following co-culture on untransfected mouse fibroblasts. In contrast to HMEC-1 cells, the CD40LG and CD31-expressing fibroblasts also induced ZAP70 expression and marked CLL cell proliferation as evidenced by carboxyfluorescein succinimidyl ester labelling and increased Ki-67 expression. Taken together, our data show that co-culture on different stroma induced a remarkably similar activation phenotype in CLL cells but only the CD40LG and CD31-expressing fibroblasts increased ZAP70 expression and CLL cell proliferation, indicating that ZAP70 may play a critical role in this process. This comparative study reveals a number of striking similarities between the co-culture systems tested but also highlights important differences that should be considered when selecting which system to use for in-vitro investigations.     

Recovery of educational skills following paediatric traumatic brain injury

Academic success in the classroom is often dependent upon a child's ability in the areas of literacy, such as reading and spelling, and arithmetic. Following traumatic brain injury these skills are often compromised. The present study examined the recovery of educational skills (reading accuracy, reading comprehension, spelling and arithmetic) over 24 months post-injury, in a group of children who had sustained a mild, moderate or severe TBI. Results showed that the severe TBI group exhibited greater deficits on reading comprehension and arithmetic, while the moderate and severe TBI groups performed similarly in the areas of reading accuracy and spelling. Future research is required to further investigate predictors of educational outcome post-TBI.     

Enzyme Immunoassay: Binding of Salmonella Antigens to Activated Microtiter Plates

Abstract

A heat extract prepared from radiolabeled Salmonella cells was used to determine if covalent binding to activated surface of polystyrene plates would improve antigen retention thus contributing to increase sensitivity in an enzyme immunoassay for Salmonella antigen. The effect of treatment with ethylchloroformate on the retention of antigens passively absorbed to polyvinylchloride and polystyrene plates was also investigated. Chemically modified plates retained more radiolabeled antigens after washing than did untreated plates in which the antigens had been physically adsorbed. However, improvement of assay sensitivity depended on the type of plate used for covalent binding of antigen. N-succiniraidyl 3-(2-pyridyldlthio) propionate (SPDP), was found to be potentially useful for mediation of covalent binding of antigens to activated plates.     

Long-term Results of Rectal Cancer Surgery with a Systematical Operative Approach

Background

Variabilities of both oncologic and functional outcomes are major problems after rectal cancer treatment. Standardized techniques might produce more consistent surgical quality. This study reports outcomes during a 20-year period resulting from a systematically applied surgical approach.

Methods

Between 1990 and 2010, 368 rectal cancer patients, treated with total mesorectal excision conducted in a standardized, stepwise approach, were prospectively entered into a database. Influence of time period, surgeon, tumor and anastomotic height, and resection type was evaluated with multivariable regression analyses adjusting for age, disease stage, diversion, and (neo)adjuvant treatment. Function outcome questionnaires were sent to 50 patients at least 5 years after surgery.

Results

Five-year overall survival was 76.4 %. Local and distant recurrence rates were 5.2 % and 22.1 %. Anastomotic leakage occurred in 5.4 % of patients treated with low anterior resection (n = 259). Time period, surgeon, tumor and anastomotic height, diversion, and abdominoperineal resection were not independent risk factors for any of these outcome measures. Both preoperative and postoperative radiotherapy were independently associated with increased risk of metastases (P = 0.035, hazard ratio (HR) = 3.04; and P = 0.029, HR = 3.59). Function questionnaires were completed by 38 of 50 patients (76 %). One of 13 nonirradiated patients reported mild fecal incontinence compared with 20 of 25 irradiated patients reporting mostly moderate-severe incontinence (P < 0.001).

Conclusions

Systematically applied surgical dissection results consistently in excellent oncologic outcomes with enhanced function outcomes. The findings suggest that in the presence of highly disciplined surgery, radiotherapy might make a smaller contribution to oncologic outcome, while leading to serious adverse effects.     

Dental students' perceptions of dental specialties and factors influencing specialty and career choices

The goals of this study were to 1) evaluate dental students' perceptions of dental specialties, 2) identify factors that play an important role in students' decision to pursue specialty training or career choices, and 3) establish a baseline of students' perceptions of the dental fields with the best future in terms of salary, personal and patient quality of life, and overall impact on the dental profession. Surveys were distributed to 494 students at the University of Pennsylvania School of Dental Medicine. Data were collected from 380 traditional four-year students and thirty advanced standing students. Chi-square tests, multivariate analysis, and logistic regressions were used to determine associations and independent contributions of student demographics to their perceptions of dental specialties and factors influencing specialty training or career choices. Debt was a statistically significant factor (p<0.001) in choosing specialty training or career independent of gender, age, or class year. Enjoyment of providing care in a specialty or field was identified as the single most important factor in choosing a specialty career. Half of the respondents had decided not to specialize. Pursuing postdoctoral general dentistry training and private practice in general dentistry were the most commonly reported plans after completion of dental school. Suggestions are made for ways to inform students about specialty training.     

Informativeness of the spoken narratives of younger and older adolescents with specific language impairment and their counterparts with normal language

A large body of literature describing the narrative skills of young children with and without language impairments exists. However, there has been only limited study of the informativeness of narratives of adolescents with normally developing language (NL) and those of adolescents with specific language impairment (SLI), even though narratives play an important role in adolescents' complex social and academic lives and there is emerging evidence that narrative abilities in young children portend their later language proficiency. This study examined the informativeness of oral narratives produced by four groups of adolescents: younger adolescents with NL (mean age = 13years:2 months), older adolescents with NL (15:10), younger adolescents with SLI (13:2) and older adolescents with SLI (15:9). The results indicated that the narratives produced by the SLI adolescents consisted of fewer informative and more irrelevant/inaccurate responses than the narratives of their peers with NL. The SLI adolescents also tended to give more vague responses in their narratives than their NL counterparts, as well tending not to provide any responses to the pictures representing the story. Taken together, these results painted a picture of SLI adolescents producing less satisfying, complete, and cohesive narratives, findings consistent with those of the research on children with SLI. Language status more than age appeared to be the factor that affected the likelihood of the adolescents providing or not providing informative responses. These results suggested that the performance of adolescents with SLI may not catch up to the level of performance of their NL counterparts during adolescence.     

Educational skills: Long-term outcome and predictors following paediatric traumatic brain injury

Given that reading, spelling and arithmetic skills are acquired through childhood, their development may be compromised following a childhood traumatic brain injury (TBI). The present study examined educational skills (reading accuracy, spelling and arithmetic) at a mean follow-up interval of 6.8 years post-injury in children who had sustained a mild, moderate, or severe TBI at two ages: ‘Young’ (age at injury: 3–7 years, n = 48) and ‘Old’: (age at injury: 8–12 years, n = 36). Comparisons between the young and old TBI groups resulted in inconsistent findings. While a dose-response relationship for severity was evident for the young group, this was not always the case for the old group. Significant predictors of outcome included both severity and acute intellectual function.