Citations

This study's aims were to describe the spirituality of depressed elderly psychiatric inpatients and to examine associations among spirituality, depression, and quality of life (QOL). Forty-five persons participated. Most reported frequent, stable spiritual practices and experiencing spiritual comfort and guidance. Some reported spiritual distress and changes in spirituality. During hospitalization, participants demonstrated increased spiritual well-being (SWB) and peacefulness, and reduced hopelessness, worthlessness, and guilt. Positive associations were found between SWB and QOL and negative associations between SWB and depression.

AbstractAbstract In a randomized trial of 130 surgical patients, use of a decision aid consisting of laminated cards with pros and cons of continuing smoking, attempting temporary abstinence, or attempting to quit smoking improved measures of decisional quality but did not change perioperative tobacco use behavior. Background: Decision aids can increase patient involvement in decision-making about health care. The study goal was to develop and test a decision aid for use by clinicians in discussion options for changing smoking behavior before and after elective surgery. Methods: In formative work, a decision aid was designed to facilitate patient–clinician discussion regarding three options: continue smoking, attempt a period of temporary abstinence, and attempt to quit smoking for good. A randomized, two-group pilot study was then conducted in smokers evaluated in preparation for elective surgery in a preoperative clinic to test the hypothesis that the decision aid would improve measures of decisional quality compared with usual care. Results: The final decision aid consisted of three laminated cards. The front of each card included a colorful graphic describing each choice; the reverse including two to three pros and cons for each decision, a simple graphic illustrating the effects of smoking on the body, and a motivational phrase. In the randomized trial of 130 patients, the decision aid significantly ( P < 0.05) improved measures of decisional quality and patient involvement in decision making (Cohen’s d effect sizes of 0.76 and 1.20 for the Decisional Conflict Scale and Observing PatienT involvement In decisiON-making scale, respectively). However, the decision aid did not affect any aspect of perioperative smoking behavior, including the distribution of or adherence to choices. Conclusions: Although the use of a decision aid to facilitate clinician–patient discussions regarding tobacco use around the time of surgery substantially improved measures of decisional quality, it alone did not change perioperative tobacco use behavior.

Abstract The mechanisms by which ovarian cancer cells are released from the primary tumor, seed throughout the peritoneal cavity, attach to local organs, and then invade these organs, are not understood. In this study, the cell adhesion molecule, Nectin-4, was investigated as a potential mediator of several steps involved in ovarian cancer progression. In particular, due to the ability of Nectin-4 to promote cell-cell adhesions, we were interested in determining its role in mediating the formation of cell-cell aggregates (spheroids) which are commonly seen in the peritoneal fluid of ovarian cancer patients. Furthermore, since spheroids are known to have a decreased rate of cell proliferation and are chemoresistant, we were also interested in the role of Nectin-4 in ovarian cancer cell proliferation and invasion. In our previous studies, we performed gene microarray analysis and identified Nectin-4 overexpression in ovarian cancer tissues compared to normal ovaries and other normal tissues. By ELISA, we found soluble Nectin-4 in the sera of 50% of women with ovarian cancer. In this study, we performed a series of experiments in which two human ovarian cancer cells lines were transfected with Nectin-4 or shRNA targeting Nectin-4, and then the resultant cells were tested in functional assays. In the first case, MA148 cells, which do not express Nectin-4, were transfected with full-length Nectin-4. The resultant MA148 cells which expressed high levels of Nectin-4 showed an increased rate of proliferation compared to control cells which did not express Nectin-4. They also formed the initial cell-cell adhesions involved in spheroid formation faster than control cells. Furthermore, the spheroids which expressed Nectin-4 were slower to disaggregate and invade through monolayers of mesothelial cells. In the second case, NIH:OVCAR5 cells, which express moderate levels of Nectin-4, were transfected with shRNA targeting Nectin-4, resulting in the partial knockdown of Nectin-4 expression. We found that the NIH:OVCAR5 cells that express lower levels of Nectin-4 on their surface required a substantially longer time to form spheroids and migrated more slowly in a wound healing assay. In both cases, we verified the expression of Nectin-4 in the transfected cells by Western immunoblotting and flow cytometry. These results suggest that Nectin-4: (a) is important in the early events of cell-cell adhesion, (b) plays a role in multicellular aggregation within the ascites of ovarian cancer patients, and (c) causes tight spheroid formations that may impede disaggregation. Additional functional studies leading to a better understanding of the role of Nectin-4 overexpression and shedding in ovarian cancer are currently underway. Understanding the role of Nectin-4 in ovarian cancer progression is critical in order to facilitate its development as a novel therapeutic target for ovarian cancer. Citation Format: Kristin L. Boylan, Adam Meyer, Petra C. Buchanan, Melissa S. DeRycke, Amy P. Skubitz. Role of nectin-4 in the progression of ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1984. doi:10.1158/1538-7445.AM2014-1984

Abstract Introduction: Peripheral blood leukocyte (PBL) telomere length is associated with colon cancer (CC) risk, but the relationship of PBL telomere length to survival in CC patients receiving chemotherapy is unknown. Methods: We measured relative telomere length (RTL) by qPCR of PBL DNA from 2,748 cases (53% male, 85% white, median age 58 yrs) in the North American Phase III Intergroup Trial N0147 that compared disease-free survival (DFS) among completely resected Stage III CC treated with mFOLFOX6 +/- cetuximab. Tumor markers were assessed, and 12% were BRAF mutant; 35% Kras mutant, and 12% deficient mismatch repair (dMMR). Linear and non-linear prognostic associations of PBL RTL to the primary endpoint of DFS were assessed by Cox models. Optimal categories of RTL were developed using cumulative martingale residual plots, designated from shortest to longest RTL (Table 1). Results: Never smokers had longer PBL RTL (p = 0.0006) than past or current smokers. Those with diabetes mellitus (DM) had longer PBL RTL than those without DM (p = 0.0165). PBL RTL was not associated with any tumor markers (MMR status; p = 0.7174; BRAF mutant vs wild-type (wt); p =0.4039; Kras mutant vs wt; p= 0.1149). PBL RTL was significantly associated with DFS in a non-linear form (p = 0.0389). Cases in the longer RTL category had more favorable DFS than those with shorter or longest RTL, (Table), which remained after adjusting for age, sex , T/N stage, grade, tumor markers, and treatment (p = 0.0230). We observed no significant interaction (p = 0.1490) between RTL categories and treatment. Conclusion: We observed a non-linear association between RTL and DFS in stage III CC, suggesting that an optimal range telomere length can influence tumor behavior in CC patients. Future studies of telomere maintenance mechanisms may help to explain the association of RTL with improved DFS. RTL is associated with smoking and DM in CC cases but further studies are needed to determine if either tobacco use or DM affect survival from CC by modulating PBL telomere length. Citation Format: Nivedita Basu, Ruth A. Johnson, Qian Shi, Garth D. Nelson, Julie M. Cunningham, Richard M. Goldberg, Frank A. Sinicrope, Daniel J. Sargent, Steven R. Alberts, Gloria M. Petersen, Stephen N. Thibodeau, Halcyon G. Skinner, Kristin Litzelman, Songwon Seo, Russell J. Vanderboom, Ronald E. Gangnon, Corinne D. Engelman, David N. Rider, Lisa A. Boardman. Telomeres and survival in stage III colon cancers: Findings from NCCTG N0147 (Alliance) study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5102. doi:10.1158/1538-7445.AM2014-5102

Abstract Background: Nulliparity is an established endometrial cancer risk factor, but whether this association is related to infertility is unclear. Although there are many underlying causes of infertility, few studies have assessed risk relationships according to specific causes. Despite concerns that most treatments induce ovulation and that the endometrium is highly hormonally-responsive, previous studies have provided conflicting results on treatment associations. Methods: To address these issues, we conducted a pooled analysis of 8,151 cases and12,471 controls from 2 cohort and 12 case-control studies conducted in 1982 to 2009 (N. America, Europe, Australia, Asia). All studies provided self-reported infertility, causes and treatments, except for 1 study that relied on data from national registries. Study-specific exposures and covariate data were harmonized across studies. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusted for study, age, interview year, race, parity, oral contraceptive and menopausal hormone use, and body mass index. If data were not reported for a particular variable, that study was excluded from the variable-specific analysis. Results: Nulliparous women had an elevated endometrial cancer risk compared with parous women (adjusted OR=1.73; 95% CI: 1.58-1.90).Women with self-reported infertility also had an increased risk (adjusted OR=1.22; 95% CI: 1.13-1.32) compared with those without infertility issues, even after adjusting for parity; the strongest associations was seen among studies that defined infertility as unsuccessfully trying to conceive for 2+ years (adjusted OR=1.31; 95% CI: 1.07-1.60). Infertility was associated with similar risks among nulliparous (1.22; 1.10-1.48) and parous (1.22; 1.12-1.34) women, although there was no increased risk associated with infertility among those who had given birth to 3+ children. Two infertility causes associated with risk elevation were endometriosis (adjusted OR=2.08; 95% CI: 1.46-2.95 compared with women no infertility problems) and anovulation (adjusted OR=1.40; 95% CI: 1.16-1.70). Based on relatively small numbers, none of the individual treatments (in vitro fertilization, selective estrogen response modulators, gonatropins, progestins, estrogens) were substantially related to risk. Conclusion: Based on mainly self-reported infertility data, we found that parity and infertility independently contribute to endometrial cancer risk, with parity seemingly being the predominant risk predictor. Understanding residual endometrial cancer relationships related to causes of infertility and infertility treatment may benefit from documented medical information on causes of infertility and treatment parameters. Citation Format: Hannah P. Yang, Linda S. Cook, Elisabete Weiderpass, Hans-Olov Adami, Kristin E. Anderson, Hui Cai, James R. Cerhan, Tess Clendenen, Ashley S. Felix, Christine Friedenreich, Montserrat Garcia-Closas, Marc T. Goodman, Xiaolin Liang, Jolanta Lissowska, Lingeng Lu, Anthony M. Magliocco, Susan E. McCann, Kristen B. Moysich, Sara H. Olson, Malcolm C. Pike, Silvia Polidoro, Fulvio Ricceri, Harvey Risch, Carlotta Sacerdote, V. Wendy Setiawan, Xiao Ou Shu, Amanda B. Spurdle, Britton Trabert, Penelope M. Webb, Nicolas Wentzensen, Yong-Bing Xiang, Youming Xu, Herbert Yu, Anne Zeleniuch-Jacquotte, Louise A. Brinton. Infertility and risk of incident endometrial carcinoma: a pooled analysis from the Epidemiology of Endometrial Cancer Consortium. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2167. doi:10.1158/1538-7445.AM2014-2167

Accurate quantification of subtle wrist motion changes resulting from ligament injuries is crucial for diagnosis and prescription of the most effective interventions for preventing progression to osteoarthritis. Current imaging techniques are unable to detect injuries reliably and are static in nature, thereby capturing bone position information rather than motion which is indicative of ligament injury. A recently developed technique, 4D (three dimensions + time) computed tomography (CT) enables three-dimensional volume sequences to be obtained during wrist motion. The next step in successful clinical implementation of the tool is quantification and validation of imaging biomarkers obtained from the four-dimensional computed tomography (4DCT) image sequences. Measures of bone motion and joint proximities are obtained by: segmenting bone volumes in each frame of the dynamic sequence, registering their positions relative to a known static posture, and generating surface polygonal meshes from which minimum distance (proximity) measures can be quantified. Method accuracy was assessed during in vitro simulated wrist movement by comparing a fiducial bead-based determination of bone orientation to a bone-based approach. The reported errors for the 4DCT technique were: 0.00–0.68 deg in rotation; 0.02–0.30 mm in translation. Results are on the order of the reported accuracy of other image-based kinematic techniques.

Dynamic loading on articular joints is essential for the evaluation of the risk of the articulation degeneration associated with occupational activities. In the current study, we analyzed the dynamic constraint loading for the thumb during pipetting. The constraint loading is considered as the loading that has to be carried by the connective tissues of the joints (i.e., the cartilage layer and the ligaments) to maintain the kinematic constraints of the system. The joint loadings are solved using a classic free-body approach, using the external loading and muscle forces, which were obtained in an inverse dynamic approach combined with an optimization procedure in anybody. The constraint forces in the thumb joint obtained in the current study are compared with those obtained in the pinch and grasp tests in a previous study (Cooney and Chao, 1977, “Biomechanical Analysis of Static Forces in the Thumb During Hand Function,” J. Bone Joint Surg. Am., 59(1), pp. 27–36). The maximal compression force during pipetting is approximately 83% and 60% greater than those obtained in the tip pinch and key pinch, respectively, while substantially smaller than that obtained during grasping. The maximal lateral shear force is approximately six times, 32 times, and 90% greater than those obtained in the tip pinch, key pinch, and grasp, respectively. The maximal dorsal shear force during pipetting is approximately 3.2 and 1.4 times greater than those obtained in the tip pinch and key pinch, respectively, while substantially smaller than that obtained during grasping. Our analysis indicated that the thumb joints are subjected to repetitive, intensive loading during pipetting, compared to other daily activities.

Abstract Background: Cigarette smoking (smoking), hormone therapy (MHT), and folate intake (folate) are each thought to influence colorectal cancer risk, but the underlying molecular mechanisms remain incompletely defined. Expression of estrogen receptor β (ESR2) has been associated with colorectal cancer stage and survival. Methods: In this prospective cohort study, we examined smoking, MHT, and folate-associated colorectal cancer risks by ESR2 protein expression level among participants in the Iowa Women's Health Study (IWHS). Self-reported exposure variables were assessed at baseline. Archived, paraffin-embedded colorectal cancer tissue specimens were collected and evaluated for ESR2 protein expression by IHC. Multivariate Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI) for associations between smoking, MHT, or folate and ESR2-defined colorectal cancer subtypes. Results: Informative environmental exposure and protein expression data were available for 491 incident colorectal cancer cases. Positive associations between ESR2-low and -high tumors and several smoking-related variables were noted, most prominently with average number of cigarettes per day (RR, 4.24; 95% CI, 1.81–9.91 for ESR2-low and RR, 2.15; 95% CI, 1.05–4.41 for ESR2-high for ≥40 cigarettes compared with nonsmokers). For MHT, a statistically significant association with ESR2-low tumors was observed with longer duration of exposure (RR, 0.54; 95% CI, 0.26–1.13 for &gt;5 years compared with never use). No associations were found for folate. Conclusions: In this study, smoking and MHT were associated with ESR2 expression patterns. Impact: These data support possible heterogeneous effects from smoking and MHT on ERβ-related pathways of colorectal carcinogenesis in older women. Cancer Epidemiol Biomarkers Prev; 24(4); 713–9. ©2015 AACR.