Single nucleotide polymorphisms in nucleotide excision repair genes,cancer treatment,and head and neck cancer survival

Purpose

Head and neck cancers (HNC) are commonly treated with radiation and platinum-based chemotherapy, which produce bulky DNA adducts to eradicate cancerous cells. Because nucleotide excision repair (NER) enzymes remove adducts, variants in NER genes may be associated with survival among HNC cases both independently and jointly with treatment.

Methods

Cox proportional hazards models were used to estimate race-stratified (White, African American) hazard ratios (HRs) and 95 % confidence intervals for overall (OS) and disease-specific (DS) survival based on treatment (combinations of surgery, radiation, and chemotherapy) and 84 single nucleotide polymorphisms (SNPs) in 15 NER genes among 1,227 HNC cases from the Carolina Head and Neck Cancer Epidemiology Study.

Results

None of the NER variants evaluated were associated with survival at a Bonferroni-corrected alpha of 0.0006. However, rs3136038 [OS HR = 0.79 (0.65, 0.97), DS HR = 0.69 (0.51, 0.93)] and rs3136130 [OS HR = 0.78 (0.64, 0.96), DS HR = 0.68 (0.50, 0.92)] of ERCC4 and rs50871 [OS HR = 0.80 (0.64, 1.00), DS HR = 0.67 (0.48, 0.92)] of ERCC2 among Whites, and rs2607755 [OS HR = 0.62 (0.45, 0.86), DS HR = 0.51 (0.30, 0.86)] of XPC among African Americans were suggestively associated with survival at an uncorrected alpha of 0.05. Three SNP-treatment joint effects showed possible departures from additivity among Whites.

Conclusions

Our study, a large and extensive evaluation of SNPs in NER genes and HNC survival, identified mostly null associations, though a few variants were suggestively associated with survival and potentially interacted additively with treatment.     

Bi‐layered living cellular construct resulted in greater healing in an alloxan‐induced diabetic porcine model

Tissue‐engineered skin constructs, including bi‐layered living cellular constructs (BLCC) used in the treatment of chronic wounds, are structurally/functionally complex. While some work has been performed to understand their mechanisms, the totality of how BLCC may function in wound healing remains unknown. To this end, we have developed a delayed wound healing model to test BLCC cellular and molecular mechanisms of action. Diabetes was chemically‐induced using alloxan in Yucatan miniature pigs, and full‐thickness wounds were generated on their dorsum. These wounds were either allowed to heal by secondary intention alone (control) or treated with a single or multiple treatments of a porcine autologous BLCC. Results indicated a single treatment with porcine BLCC resulted in statistically significant wound healing at day 17, while four treatments resulted in statistically significant healing on days 10, 13, and 17 compared to control. Statistically accelerated wound closure was driven by re‐epithelialisation rather than contraction or granulation. This porcine diabetic model and the use of a porcine BLCC allowed evaluation of healing responses in vivo without the complications typically seen with either xenogenic responses of human/animal systems or the use of immune compromised animals, expanding the knowledge base around how BLCC may impact chronic wounds.     

Cancellation of elective oral and maxillofacial operations

Our aim was to assess whether the Commission for Health Improvement Performance Indicator value of 0.5% of cancellations on the day of operation or less had been achieved. We reviewed 912 consecutive elective operations, both day case and inpatient over an 8-month period (January–August 2003). A total of 117 procedures (13%) were cancelled for non-clinical or logistical reasons, of which 39 (4%) were cancelled on the day of the operation. Only 3 of the 39 patients who wanted a new admission date within 28 days of cancellation could not be accommodated. The performance indicator value of 0.3% was below the target threshold. An additional 60 (7%) patients had their admissions cancelled the day before operation and 18 (2%) had their operations deferred for a day before they were cancelled. However, these patients have been specifically excluded from the performance indictor.     

Targeting Lifestyle Behavior Change in Adults with NAFLD During a 20-min Consultation: Summary of the Dietary and Exercise Literature

Non-alcoholic fatty liver disease (NAFLD) is largely linked to poor diet, lack of physical activity/exercise, and being overweight. In the absence of approved pharmaceutical agents, lifestyle modification, encompassing dietary change and increased physical activity/exercise to initiate weight loss, is the recommended therapy for NAFLD. Despite this, the use of lifestyle therapy within clinical settings is lacking with limited guidance available about what it should involve, how it should be delivered, and whether it can be feasibly delivered as part of standard care. This paper highlights the evidence for the use of lifestyle modification in NAFLD. While there is evidence to support use of behavioral strategies to support lifestyle behavior change in other clinical populations, these are yet to be assessed in people with NAFLD. However, there is sufficient evidence to suggest that behavioral intervention targeting diet and physical activity to promote weight loss in general is effective and a number of practical strategies are presented on how this could be achieved.     

Keeping the body in mind: Insula functional organization and functional connectivity integrate interoceptive,exteroceptive, and emotional awareness

Relatively discrete experimental literatures have grown to support the insula's role in the domains of interoception, focal exteroceptive attention and cognitive control, and the experience of anxiety, even as theoretical accounts have asserted that the insula is a critical zone for integrating across these domains. Here we provide the first experimental demonstration that there exists a functional topography across the insula, with distinct regions in the same participants responding in a highly selective fashion for interoceptive, exteroceptive, and affective processing. Although each insular region is associated with areas of differential resting state functional connectivity relative to the other regions, overall their functional connectivity profiles are quite similar, thereby providing a map of how interoceptive, exteroceptive, and emotional awareness are integrated within the insular cortex. Hum Brain Mapp 34:2944–2958, 2013. © 2012 Wiley Periodicals, Inc.