CDC25B and CDC25C overexpression in nonmelanoma skin cancer suppresses cell death

Non‐melanoma skin cancer frequently results from chronic exposure to ultraviolet (UV) irradiation. UV‐induced DNA damage activates cell cycle arrest checkpoints through degradation of the cyclin‐dependent kinase activators, the cell division cycle 25 (CDC25) phosphatases. We previously reported increased CDC25A in nonmelanoma skin cancer, but CDC25B and CDC25C had not been previously examined. Consequently, we hypothesized that increased expression of CDC25B and CDC25C increases tumor cell proliferation and skin tumor growth. We found that CDC25B and CDC25C were increased in mouse and human skin cancers. CDC25B was primarily cytoplasmic in skin and skin tumors and was significantly increased in the squamous cell carcinoma (SCC), while CDC25C was mostly nuclear in the skin, with an increased cytoplasmic signal in the premalignant and malignant tumors. Surprisingly, forced expression of CDC25B or CDC25C in cultured SCC cells did not affect proliferation, but instead suppressed apoptosis, while CDC25C silencing increased apoptosis without impacting proliferation. Targeting CDC25C to the nucleus via mutation of its nuclear export sequence, however, increased proliferation in SCC cells. Overexpression of CDC25C in the nuclear compartment did not hinder the ability of CDC25C to suppress apoptosis, neither did mutation of sites necessary for its interaction with 14‐3‐3 proteins. Analysis of apoptotic signaling pathways revealed that CDC25C increased activating phosphorylation of Akt on Ser⁴⁷³, increased inhibitory phosphorylation of proapoptotic BAD on Ser¹³⁶, and increased the survival protein Survivin. Silencing of CDC25C significantly reduced Survivin levels. Taken together, these data suggest that increased expression of CDC25B or CDC25C are mechanisms by which skin cancers evade apoptotic cell death.     

Introducing dental students to clinical patient care: The complete denture prosthodontics transition clinic

Using complete denture treatment as an introduction to clinical patient care for dental students, the purposes of the Complete Denture Prosthodontics Transition Clinic at the University of Colorado School of Dentistry are to reduce the time lapse between the preclinical complete denture prosthodontics course and the first denture patient experience, and to encourage development of student self-confidence and skills. In the 2002 spring semester, faculty at the University of Colorado School of Dentistry initiated the Complete Denture Prosthodontics Transition Clinic for DS-II (second-year) dental students, as an introduction to clinical patient care. Each patient was assigned to a team of two dental students. Three Division of Prosthodontics faculty members staffed each clinic session, providing a student-to-faculty ratio of approximately 6.6:1 and a patient-to-faculty ratio of approximately 3.3:1. All DS-II students in the Class of 2004 delivered their first complete dentures no later than 8 months (average, 184 days) after the last day of the preclinical complete denture prosthodontics course. The time from the diagnostic appointment through the denture placement appointment averaged 39 days for patients treated in this program, compared with an average of 98 days or more for previous classes. The program was successful in achieving the goal of reducing the time lapse between the preclinical complete denture prosthodontics course and the first denture patient experience.     

A new index for evaluating horizontal skeletal discrepancies and predicting treatment outcomes

The cephalometric measurement known as Wits appraisal (AOBO) was studied to determine its importance in diagnosis, treatment, and prediction of treatment success. The Wits appraisal is used primarily to identify unreliable ANB values (those that do not accurately reflect the degree of horizontal jaw discrepancy, ie, those that differ greatly from the AOBO value). Therefore, differences between AOBO and ANB also were evaluated. Because neither measurement alone can assess jaw discrepancies with total accuracy, they were combined, plotted on a scattergram, and divided into equal zones to create a new index of horizontal skeletal discrepancies and treatment predictability. Pretreatment values correspond to treatment difficulty, and posttreatment values correspond to the effectiveness of treatment. Treatment time for each zone also was evaluated. We were able to draw several conclusions from this study. First, combining AOBO and ANB values results in a more accurate measurement of treatment difficulty. These combined values also can be used to predict both treatment time and the success of treatment for horizontal discrepancies. Second, the AOBO value predicts variations in treatment time at each ANB value. Finally, adding ANB and AOBO values and then dividing the total yields zones that represent statistically significant differences in treatment times and percentages of success. The zones also correlate with the difference between AOBO and ANB measurements.     

Two approaches to social support in smoking cessation: Commodity model and nondirective support

The commodity model of social support and features of Nondirective Support may clarify varied results of support interventions for smoking cessation. A commodity model views social support as attractive in and of itself and as an alternative to high-risk choices such as smoking. If such support is easily accessible, a would-be quitter is less likely to choose to smoke. Consistent with the commodity model, social support interventions tend to be effective as long as support remains available, but they lose their effects when support is terminated. From a second approach, Nondirective Support entails accepting recipients' goals, cooperating without taking control, and validating recipients' feelings. In contrast, Directive Support entails taking control and telling recipients what to do and feel. Review of support interventions indicates the value of the continued availability of support suggested by the commodity model and of Nondirective Support's flexibility and responsiveness to the person.     

Partner- and partnership-related risk factors for preterm birth among low-income women in Lima,Peru

A woman's partner and the characteristics of their partnership can play an important role in the health of her pregnancy. Yet, with the notable exception of intimate partner violence, there has been little previous research addressing the associations between partner- or partnership-related factors and birth outcomes. This analysis tested the hypothesis that risk factors related specifically to partner or partnership characteristics increased the risk for preterm birth. Between 2003 and 2005, a total of 580 preterm cases (20–36 weeks gestational age at delivery) and 633 term controls (≥37 weeks) were selected from women delivering at an obstetric hospital in Lima, Peru. Each woman completed a confidential, structured interview and provided biological specimens within 48 h after delivery. Multivariable logistic regression was used to assess associations between partner and partnership characteristics and preterm birth. After adjustment for behavioral, demographic, and obstetric risk factors, ever having had a partner with a history of drug use (aOR = 1.91, 95% CI 1.22–2.99), ever having had anal sex (aOR = 1.40, 95% CI 1.07–1.84), having a current partner with a history of visiting prostitutes (aOR = 1.69, 95% CI 1.22–2.33), and perceiving one's current partner as a “womanizer” (aOR = 1.34, 95% CI 1.02–1.77) were significantly associated with an elevated risk of preterm birth when tested in separate models. These four factors were then used to create a composite partnership risk score, which showed an increasing dose-response relationship with preterm birth risk (per additional partner risk factor: aOR = 1.31, 95% CI 1.16–1.49). These results highlight the importance of considering a broader set of risk factors for preterm birth, specifically those related to a woman's partner and partnership characteristics. Further research could clarify the specific mechanisms through which these partner and partnership characteristics may increase the risk of preterm birth.     

Balloon angioplasty in acute and chronic coronary artery disease

Percutaneous transluminal coronary angioplasty has grown exponentially since its introduction. Currently, selection criteria include single-vessel and multivessel disease, stable and unstable angina, and acute infarction. The outcome depends on specific patient and angiographic characteristics. In ideal lesions, success rates should be greater than 90%, with low morbidity and mortality. With more severe and diffuse multivessel disease, success rates are lower and complication rates are higher. In these cases, percutaneous transluminal coronary angioplasty still offers a reasonable option, provided complete revascularization can be achieved or the angina-producing lesion dilated. Numerous issues remain unresolved, including (1) the role of percutaneous transluminal coronary angioplasty vs coronary surgery (currently being tested), (2) restenosis, which occurs in approximately 30% of treated lesions, and (3) organizational adjustments such as training and certification to maintain high standards of care.