Neuroligin-1 knockdown reduces survival of adult-generated newborn hippocampal neurons

Survival of adult-born hippocampal granule cells is modulated by neural activity, and thought to be enhanced by excitatory synaptic signaling. Here, we report that a reduction in the synaptogenic protein neuroligin-1 in adult-born neurons in vivo decreased their survival, but surprisingly, this effect was independent of changes in excitatory synaptic function. Instead, the decreased survival was associated with unexpected changes in dendrite and spine morphology during granule cell maturation, suggesting a link between cell growth and survival

Evaluation of easily measured risk factors in the prediction of osteoporotic fractures

BACKGROUND: Fracture represents the single most important clinical event in patients with osteoporosis, yet remains under-predicted. As few premonitory symptoms for fracture exist, it is of critical importance that physicians effectively and efficiently identify individuals at increased fracture risk. METHODS: Of 3426 postmenopausal women in CANDOO, 40, 158, 99, and 64 women developed a new hip, vertebral, wrist or rib fracture, respectively. Seven easily measured risk factors predictive of fracture in research trials were examined in clinical practice including: age (<65, 65–69, 70–74, 75–79, 80+ years), rising from a chair with arms (yes, no), weight (< 57, ≥ 57kg), maternal history of hip facture (yes, no), prior fracture after age 50 (yes, no), hip T-score (>-1, -1 to >-2.5, ≤-2.5), and current smoking status (yes, no). Multivariable logistic regression analysis was conducted. RESULTS: The inability to rise from a chair without the use of arms (3.58; 95% CI: 1.17, 10.93) was the most significant risk factor for new hip fracture. Notable risk factors for predicting new vertebral fractures were: low body weight (1.57; 95% CI: 1.04, 2.37), current smoking (1.95; 95% CI: 1.20, 3.18) and age between 75–79 years (1.96; 95% CI: 1.10, 3.51). New wrist fractures were significantly identified by low body weight (1.71, 95% CI: 1.01, 2.90) and prior fracture after 50 years (1.96; 95% CI: 1.19, 3.22). Predictors of new rib fractures include a maternal history of a hip facture (2.89; 95% CI: 1.04, 8.08) and a prior fracture after 50 years (2.16; 95% CI: 1.20, 3.87). CONCLUSION: This study has shown that there exists a variety of predictors of future fracture, besides BMD, that can be easily assessed by a physician. The significance of each variable depends on the site of incident fracture. Of greatest interest is that an inability to rise from a chair is perhaps the most readily identifiable significant risk factor for hip fracture and can be easily incorporated into routine clinical practice

Unit Nonresponse in a Population-Based Study of Prostate Cancer

Low unit response rates can increase bias and compromise study validity. Response rates have continued to fall over the past decade despite all efforts to increase participation. Many factors have been linked to reduced response, yet relatively few studies have employed multivariate approaches to identify characteristics that differentiate respondents from nonrespondents since it is hard to collect information on the latter. We aimed to assess factors contributing to enrollment of prostate cancer (PCa) patients. We combined data from the North Carolina-Louisiana (LA) PCa Project’s LA cohort, with additional sources such as US census tract and LA tumor registry data. We included specific analyses focusing on blacks, a group often identified as hard to enroll in health-related research. The ability to study the effect of Hurricane Katrina, which occurred amidst enrollment, as a potential determinant of nonresponse makes our study unique. Older age (≥ 70) for blacks (OR 0.65) and study phase with respect to Hurricane Katrina for both races (OR 0.59 for blacks, OR 0.48 for whites) were significant predictors of participation with lower odds. Neighborhood poverty for whites (OR 1.53) also was a significant predictor of participation, but with higher odds. Among blacks, residence in Orleans parish was associated with lower odds of participation (OR 0.33) before Katrina. The opposite occurred in whites, with lower odds (OR 0.43) after Katrina. Our results overall underscore the importance of tailoring enrollment approaches to specific target population characteristics to confront the challenges posed by nonresponse. Our results also show that recruitment-related factors may change when outside forces bring major alterations to a population's environment and demographics

The association of diabetes and obesity with prostate cancer aggressiveness among Black Americans and White Americans in a population-based study

Few studies have investigated the role of race in the association of diabetes and obesity with prostate cancer aggressiveness. Here we evaluate the independent association between diabetes and obesity with prostate cancer aggressiveness in White Americans and Black Americans

Healthcare satisfaction in older and younger patients with cancer

Objective Although older patients represent the most rapidly growing segment of the oncology population, clinical care is guided by very little data on patient-reported outcomes, particularly satisfaction with healthcare. Using a large cancer center registry, we sought to describe factors associated with satisfaction with care for older and younger oncology patients. Methods Data were collected through the University of North Carolina Health Registry Cancer Survivorship Cohort. Satisfaction was measured with the Patient Satisfaction Questionnaire Short Form. Quality of life (QOL) measures included were the Promis Global short form and the Functional Assessment of Cancer Therapy General (FACT-G). Results A total of 2385 patients were included. 460 (20%) were aged 70 and above (older group). Older patients reported significantly higher levels of satisfaction in domains of time spent with doctor (scores 3.84 versus 3.73 p = 0.03) and financial aspects (scores 4.03 versus 3.44 p < 0.001) compared to younger patients. In multivariable analysis, higher QOL scores and higher self-reported ECOG performance status were associated with higher satisfaction scores. African American race was associated with lower satisfaction scores in all age groups. QOL was more closely correlated with satisfaction in older patients compared to younger patients. Conclusions Older patients with cancer report higher levels of satisfaction with care, in part due to lesser financial burden of care. Better QOL is associated with satisfaction with care in older patients. Use of patient-reported outcomes such as patient satisfaction may help improve patient-centered geriatric oncology care

Dietary Total Antioxidant Capacity is Inversely Associated with Prostate Cancer Aggressiveness in a Population-Based Study

The purpose of this study was to determine the relationship between total antioxidant capacity (TAC) from diet and supplements and prostate cancer aggressiveness among 855 African Americans (AA) and 945 European Americans (EA) in the North Carolina-Louisiana Prostate Cancer Project (PCaP). Cases were classified as either high aggressive, low aggressive, or intermediate aggressive. TAC was calculated from the vitamin C equivalent antioxidant capacity of 42 antioxidants measured via food frequency questionnaire. EA reported greater dietary TAC from diet and supplements combined (P 1500 vs. < 500 mg VCE/d): 0.31 (95% CI: 0.15, 0.67; P-trend < 0.01), 0.28 (95% CI: 0.08, 0.96; P-trend < 0.001), and 0.36 (95% CI: 0.15, 0.86; P-trend = 0.58), respectively. These associations did not appear to differ between AA and EA. These data suggest that greater intake of antioxidants is associated with less aggressive prostate cancer. Additional research is needed to confirm these results and determine the underlying mechanisms

Understanding the relationship between environmental arsenic and prostate cancer aggressiveness among African-American and European-American men in North Carolina

High-level exposure to arsenic, a known carcinogen and endocrine disruptor, is associated with prostate cancer (PCa) mortality. Whether low-level exposure is associated with PCa aggressiveness remains unknown. We examined the association between urinary arsenic and PCa aggressiveness among men in North Carolina. This cross-sectional study included 463 African-American and 491 European-American men with newly diagnosed, histologically confirmed prostate adenocarcinoma. PCa aggressiveness was defined as low aggressive (Gleason score &lt; 7, stage = cT1–cT2, and PSA &lt; 10 ng/mL) versus intermediate/high aggressive (all other cases). Total arsenic and arsenical species (inorganic arsenic (iAsIII + iAsV), arsenobetaine, monomethyl arsenic, and dimethyl arsenic)) and specific gravity were measured in spot urine samples obtained an average of 23.7 weeks after diagnosis. Multivariable logistic regression was used to estimate the covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for PCa aggressiveness in association with arsenic tertiles/quantiles overall and by race. The highest (vs. lowest) tertile of total arsenic was associated with PCa aggressiveness ORs of 1.77 (95% CI = 1.05–2.98) among European-American men, and 0.94 (95% CI = 0.57–1.56) among African-American men (PInteraction = 0.04). In contrast, total arsenic and arsenical species were not associated with PCa aggressiveness in unstratified models. Low-level arsenic exposure may be associated with PCa aggressiveness among European-Americans, but not among African-Americans

Lessons learned while starting multi-institutional genetics research in diverse populations: A report from the Clinical Sequencing Evidence-Generating Research (CSER) consortium

Background: Increasing diversity in clinical trial participation is necessary to improve health outcomes and requires addressing existing social, structural, and geographic barriers. The Clinical Sequencing Evidence-Generating Research Consortium (CSER) included six research projects to enroll historically underrepresented/underserved (UR/US) populations in clinical genomics research. Delays and project re-designs emerged shortly after work began. Understanding common experiences of these projects may inform future trial implementation. Methods: Semi-structured interviews with six CSER principal investigators and seven project managers were performed. An interview guide included questions of research/clinical infrastructure, logistics across sites, language, communication, and allocation of grant-related resources. Interviews were recorded, transcribed verbatim; transcripts were analyzed using inductive coding, thematic analysis and consensus building. Results: All projects collaborating with new clinical sub-sites to recruit UR/US populations. Refining trial logistics continued long after enrollment for all projects. Themes of challenges included: sub-site customization for workflow and genetics support, conflicting input from participant advisory groups and approval bodies, developing research personnel, complex data management structures, and external changes (e.g. subcontractors ending contracts) that required redesign. Themes of beneficial lessons included: domains with prior experience were easier, develop project champions at each sub-site, structure communication within the research team, and simplify research design when possible. Conclusions: The operational aspects of expanding clinical research into novel sub-sites are significant and require investment of time and resources. The themes arising from these interviews suggest priority areas for more quantitative analyses in the future including multi-institutional approval policies and processes, data management structures, and incremental research complexity

Intake of dietary antioxidants is inversely associated with biomarkers of oxidative stress among men with prostate cancer

Abstract Prostate cancer is the most common non-cutaneous cancer and the second leading cause of cancer-related mortality among men in the USA. Growing evidence suggests that oxidative stress is involved in the development and progression of prostate cancer. In this study, the association between antioxidants from diet and supplements and biomarkers of oxidative stress in blood ( n 278), urine ( n 298) and prostate tissue ( n 55) were determined among men from the North Carolina-Louisiana Prostate Cancer Project. The association between antioxidant intake and oxidative stress biomarkers in blood and urine was determined using linear regression, adjusting for age, race, prostate cancer aggressiveness and smoking status. Greater antioxidant intake was found to be associated with lower urinary 8-isoprostane concentrations, with a 10 % increase in antioxidant intake corresponding to an unadjusted 1·1 % decrease in urinary 8-isoprostane levels (95 % CI −1·7, −0·3 %; P value&lt;0·01) and an adjusted 0·6 % decrease (95 % CI −1·4, 0·2 %; P value=0·16). In benign prostate tissue, thioredoxin 1 was inversely associated with antioxidant intake ( P =0·02). No significant associations were found for other blood or urinary biomarkers or for malignant prostate tissue. These results indicate that antioxidant intake may be associated with less oxidative stress among men diagnosed with prostate cancer

Breast Cancer Subtypes and Previously Established Genetic Risk Factors: A Bayesian Approach

Gene expression analyses indicate that breast cancer is a heterogeneous disease with at least 5 immunohistologic subtypes. Despite growing evidence that these subtypes are etiologically and prognostically distinct, few studies have investigated whether they have divergent genetic risk factors. To help fill in this gap in our understanding, we examined associations between breast cancer subtypes and previously established susceptibility loci among white and African-American women in the Carolina Breast Cancer Study