Specialty Supplements and Prostate Cancer Risk in the VITamins And Lifestyle (VITAL) Cohort

Although there is evidence from studies of prostate cancer cell lines and rodent models that several supplements may have antiinflammatory, antioxidant, or other anticancer properties, few epidemiologic studies have examined the association between nonvitamin, nonmineral, “specialty” supplement use and prostate cancer risk. Participants, 50–76 yr, were 35,239 male members of the VITamins and Lifestyle (VITAL) cohort who were residents of western Washington state, and who completed an extensive baseline questionnaire in 2000–2002. Participants responded about their frequency (days/wk) and duration (yr) of specialty supplement uses. 1,602 incident invasive prostate cancers were obtained from the Surveillance, Epidemiology, and End Results registry. Multivariate-adjusted hazards ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazards models. Any use of grapeseed supplements was associated with a 41% (HR 0.59, 95% CI: 0.40–0.86) reduced risk of total prostate cancer. There were no associations for use of chondroitin, coenzyme Q10, fish oil, garlic, ginkgo biloba, ginseng, glucosamine, or saw palmetto. Grapeseed may be a potential chemopreventive agent; however, as current evidence is limited, it should not yet be promoted for prevention of prostate cancer.     

Reservations of the Spirit: The Development of a Culturally Sensitive Spiritual Beliefs Scale About Organ Donation

This study investigated whether spiritual beliefs offered any explanation for why participants from Korea (N?=?146), Japan (N?=?134), and the United States (N?=?146) were willing or reluctant to register as organ donors. A culturally appropriate measure of spiritual beliefs about organ donation, the Spiritual Beliefs Scale, was developed consisting of 2 factors: (a) Spiritual Connection and (b) Spiritual Concern. Spiritual Connection was a significant predictor of behavioral intention to become an organ donor for Korean respondents, whereas Spiritual Concern was a significant predictor of reluctance to become an organ donor for American respondents. Spiritual beliefs correlated as predicted with attitude toward organ donation and fear of bodily mutilation, showing that the Spiritual Beliefs Scale exhibited internal, external, and predictive validity. Across the 3-country sample, Spiritual Connection was associated with greater willingness to become an organ donor for women, whereas Spiritual Concern inhibited participation for men. Implications of these findings are discussed for developing culturally effective education and procurement campaigns.     

Mother–Daughter Communication About Sex: The Influence of Authoritative Parenting Style

Parent–child communication about sex has been shown to delay sexual activity and increase contraceptive and condom use. The influence of authoritative parenting style and mothers' perception of daughters' risk on communication about sex was examined in this study. Mothers in a random sample (n?=?283) with daughters aged 9–15 years were mailed surveys asking about communication with their daughters regarding 11 sex-related topics. Multivariate linear regression was used to assess the influence of authoritative parenting style and mothers' perceptions of risk on the number of topics communicated about and age of the daughter at time of communication for a variety of sexual health communication topics. Authoritative parenting style was related to the number of topics communicated about and was a predictor of age of daughter at the time of communication about sexual intercourse, menstruation, dating/relationships, sexually transmitted diseases (STDs), HIV/AIDS, alcohol, contraceptives, and abstinence, while perceptions of risk were not significant influencers of age at the time of communication for any topics. This research points to the importance of parenting style in determining the timing of parent–child communication about sexual and other risk behaviors.     

The modifying effect of patient location on stage-specific survival following colorectal cancer using geosurvival models

Colorectal cancer (CRC) is the third leading cause of cancer death in the US, and stage at diagnosis is the primary prognostic factor. To date, the interplay between geographic place and individual characteristics such as cancer stage with CRC survival is unexplored. We used a Bayesian geosurvival statistical model to evaluate whether the spatial patterns of CRC survival at the census tract level varies by stage at diagnosis (in situ/local, regional, distant), controlling for patient characteristics, surveillance test use, and treatment using linked 1991–2005 SEER-Medicare data of patients ≥ 66 years old in two US metropolitan areas. The spatial pattern of survival varied by stage at diagnosis for both cancer sites and registries. Significant spatial effects were identified in all census tracts for colon cancer and the majority of census tracts for rectal cancer. Geographic disparities appeared to be highest for distant-stage rectal cancer. Compared to those with in situ/local stage in the same census tracts, patients with distant-stage cancer were at most 7.73 times and 4.69 times more likely to die of colon and rectal cancer, respectively. Moreover, frailty areas for CRC at in situ/local stage more likely have a higher relative risk at regional stage, but not at distant stage. We identified geographic areas with excessive risk of CRC death and demonstrated that spatial patterns varied by both cancer type and cancer stage. More research is needed to understand the moderating pathways between geographic and individual-level factors on CRC survival.     

Electrical stimulation therapy for the treatment of pressure ulcers in individuals with spinal cord injury: a systematic review and meta‐analysis

To conduct a systematic review and meta‐analysis on the effects of electrical stimulation therapy (EST) on healing pressure ulcers in individuals with spinal cord injury (SCI). CINAHL, The Cochrane Library, PubMed, SCOPUS, EMBASE, Nursing & Allied Health and Dissertation & Theses databases were searched for relevant English language articles from the date of inception to 31 January 2014. Separate searches were conducted in Google Scholar and academic journals specialised in wound care. Two reviewers independently assessed study eligibility. Studies were included if EST was used to treat pressure ulcers in individuals with SCI. A total of 599 articles were screened, and 15 studies met the inclusion criteria. A meta‐analysis with five studies demonstrated that EST significantly decreased the ulcer size by 1·32%/day [95% confidence interval (CI): 0·58–2·05, P < 0·001] compared to standard wound care (SWC) or sham EST. Another meta‐analysis conducted with four studies showed that EST increased the risk of wound healing by 1·55 times compared with standard wound care or sham EST (95% CI: 1·12 to 2·15, P < 0·0001). Because of the wide array of outcome measures across studies, a single meta‐analysis could not be conducted. EST appears to be an effective adjunctive therapy to accelerate and increase pressure ulcer closure in individuals with SCI.     

Men's involvement in antenatal screening: a qualitative pilot study using e-mail

Objectives

this study aimed to explore and analyse men's involvement in antenatal genetic screening and testing in England, and evaluate the use of e-mail communication as a method of health research with men.

Design

after receiving a favourable ethical opinion, a longitudinal qualitative pilot study was undertaken.

Participants

eight men, whose partners were pregnant, were recruited by purposive sampling.

Findings

findings indicated that the men experienced ambivalence, doubts and uncertainty about medically identified genetic risks, and also experienced an ‘emotional rollercoaster’, which was associated with their involvement in antenatal genetic screening and testing. Although connectedness with their partners and shared decision making were highly valued, men's involvement was mediated by their partners and health professionals, including midwives.

Conclusions and implications for practice

the implications of findings for medicalisation theory and future research are discussed. Using e-mail was a success in that the strong pilot data produced provides a stimulus for future research. In addition, implications for policy and practice are also considered, specifically the importance of addressing ambivalence and mediation if midwives are to communicate effectively when working with men and women regarding antenatal genetic screening and testing.     

Characterization of novel and complex genomic aberrations in glioblastoma using a 32K BAC array

Glioblastomas (GBs) are malignant CNS tumors often associated with devastating symptoms. Patients with GB have a very poor prognosis, and despite treatment, most of them die within 12 months from diagnosis. Several pathways, such as the RAS, tumor protein 53 (TP53), and phosphoinositide kinase 3 (PIK3) pathways, as well as the cell cycle control pathway, have been identified to be disrupted in this tumor. However, emerging data suggest that these aberrations represent only a fraction of the genetic changes involved in gliomagenesis. In this study, we have applied a 32K clone-based genomic array, covering 99% of the current assembly of the human genome, to the detailed genetic profiling of a set of 78 GBs. Complex patterns of aberrations, including high and narrow copy number amplicons, as well as a number of homozygously deleted loci, were identified. Amplicons that varied both in number (three on average) and in size (1.4 Mb on average) were frequently detected (81% of the samples). The loci encompassed not only previously reported oncogenes (EGFR, PDGFRA, MDM2, and CDK4) but also numerous novel oncogenes as GRB10, MKLN1, PPARGC1A, HGF, NAV3, CNTN1, SYT1, and ADAMTSL3. BNC2, PTPLAD2, and PTPRE, on the other hand, represent novel candidate tumor suppressor genes encompassed within homozygously deleted loci. Many of these genes are already linked to several forms of cancer; others represent new candidate genes that may serve as prognostic markers or even as therapeutic targets in the future. The large individual variation observed between the samples demonstrates the underlying complexity of the disease and strengthens the demand for an individualized therapy based on the genetic profile of the patient.     

Body size and ovarian cancer: case–control study and systematic review (Australia)

Objective: Although increased body mass is an established risk factor for a variety of cancers, its relation with cancer of the ovary is unclear. We therefore investigated the association between measures of body mass index (BMI) and ovarian cancer risk. Methods: Data from an Australian case–control study of 775 ovarian cancer cases and 846 controls were used to examine the association with BMI. We have also summarized the results from a number of other studies that have examined this association. Results: There was a significant increased risk of ovarian cancer with increasing BMI, with women in the top 15% of the BMI range having an odds ratio (OR) of 1.9 (95% confidence interval (CI), 1.3–2.6) compared with those in the middle 30%. Stratifying by physical activity showed a stronger effect among inactive women (OR = 3.0, 95% CI 1.3–6.9). The overall effect was consistent with the findings of most prior population-based case–control studies, while cohort studies reported positive effects closer to the null. Hospital-based studies gave variable results. Conclusions: Taken together, the evidence is in favor of a small to moderate positive relation between high BMI and occurrence of ovarian cancer.     

Stress alleviates reduced expression of cell adhesion molecules (NCAM, L1), and deficits in learning and corticosterone regulation of apolipoprotein E knockout mice

Cell adhesion molecules (CAMs) involved in synaptic changes underlying learning and memory processes, are implicated in the effect of stress on behavioural performance. The present study was designed to test the hypothesis that (i) expression of CAMs is apolipoprotein E‐ (apoE) genotype dependent and (ii) repeated exposure to stress modulates the synthesis of CAMs in an apoE‐genotype dependent manner. Using ELISA we tested this hypothesis and measured expression of NCAM and L1 in different brain regions of naïve and stressed apolipoprotein E‐knockout (apoE0/0) and C57Bl6 (wild‐type) mice. Naïve apoE0/0 mice had elevated basal morning corticosterone and ACTH concentrations and decreased expression of NCAM and L1 compared to wild‐type mice. Repeated exposure of mice to rats, as the common stressor, alleviated the reduction in expression of CAMs in apoE0/0 mice; seven days after the last rat exposure, expression of NCAM was increased in frontal brain and hippocampus whereas expression of L1 was increased in hippocampus and cerebellum. Rat stress attenuated the elevation of basal morning corticosterone concentration in apoE0/0 mice towards concentrations detected in wild‐type mice. Moreover, rat stress improved learning and memory of apoE0/0 mice in the water maze. In conclusion, repeated exposure to stress eliminated apoE‐genotype‐related differences in expression of CAMs. Under these same conditions the differences in cognitive performance and corticosterone concentrations were abolished between wild type and apoE0/0 mice.     

Pharmacometabonomic association of cyclophosphamide 4‐hydroxylation in hematopoietic cell transplant recipients

The widely used alkylating agent cyclophosphamide (CY) has substantive interpatient variability in the area under the curve (AUC) of it and its metabolites. Numerous factors may influence the drug‐metabolizing enzymes that metabolize CY to 4‐hydroxycyclophosphamide (4HCY), the principal precursor to CY’s cytotoxic metabolite. We sought to identify endogenous metabolomics compounds (EMCs) associated with 4HCY formation clearance (ratio of 4HCY/CY AUC) using global metabolomics. Patients who undergo hematopoietic cell transplantation receiving post‐transplant CY (PT‐CY) were enrolled, cohort 1 (n = 26) and cohort 2 (n = 25) donating longitudinal blood samples before they started HCT (pre‐HCT), before infusion of the donor allograft (pre‐graft), before the first dose of PT‐CY (pre‐CY), and 24 h after the first dose of PT‐CY (24‐h post‐CY), which is also immediately before the second dose of CY. A total of 512 and 498 EMCs were quantitated in two cohorts, respectively. Both univariate linear regression with false discovery rate (FDR), and pathway enrichment analyses using a global association test were performed. At the pre‐CY time point, no EMCs were associated at FDR less than 0.1. At pre‐HCT, cohort 1 had one EMC (levoglucosan) survive the FDR threshold. At pre‐graft, cohort 1 and cohort 2 had 20 and 13 EMCs, respectively, exhibiting unadjusted p values less than 0.05, with the only EMCs having an FDR less than 0.1 being two unknown EMCs. At 24‐h post‐CY, there were three EMCs, two ketones, and threitol, at FDR less than 0.1 in cohort 2. These results demonstrate the potential of pharmacometabonomics, but future studies in larger samples are needed to optimize CY.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

We report the first pharmacometabonomic study of the association of plasma EMCs with cyclophosphamide pharmacokinetics, specifically the ratio of 4HCY/CY AUC.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study addresses the question regarding if EMCs in the plasma before PT‐CY administration are associated with the ratio of 4HCY/CY AUC.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study adds to our knowledge that longitudinal collection of plasma EMC samples is feasible in HCT patients receiving PT‐CY. In addition, the plasma EMC changes over the ~21‐day time period that starts pre‐HCT to 24‐hr after the first PT‐CY dose.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

This study demonstrates the possibility of pharmacometabolomic research to evaluate the pharmacokinetics of a drug – in this case, cyclophosphamide – with a complex pharmacokinetic disposition.