Quantifiable Biomarkers of Normal Aging in the Japanese Medaka Fish (Oryzias latipes)

BACKGROUND: Small laboratory fish share many anatomical and histological characteristics with other vertebrates, yet can be maintained in large numbers at low cost for lifetime studies. Here we characterize biomarkers associated with normal aging in the Japanese medaka (Oryzias latipes), a species that has been widely used in toxicology studies and has potential utility as a model organism for experimental aging research. PRINCIPAL FINDINGS: The median lifespan of medaka was approximately 22 months under laboratory conditions. We performed quantitative histological analysis of tissues from age-grouped individuals representing young adults (6 months old), mature adults (16 months old), and adults that had survived beyond the median lifespan (24 months). Livers of 24-month old individuals showed extensive morphologic changes, including spongiosis hepatis, steatosis, ballooning degeneration, inflammation, and nuclear pyknosis. There were also phagolysosomes, vacuoles, and residual bodies in parenchymal cells and congestion of sinusoidal vessels. Livers of aged individuals were characterized by increases in lipofuscin deposits and in the number of TUNEL-positive apoptotic cells. Some of these degenerative characteristics were seen, to a lesser extent, in the livers of 16-month old individuals, but not in 6-month old individuals. The basal layer of the dermis showed an age-dependent decline in the number of dividing cells and an increase in senescence-associated β-galactosidase. The hearts of aged individuals were characterized by fibrosis and lipofuscin deposition. There was also a loss of pigmented cells from the retinal epithelium. By contrast, age-associated changes were not apparent in skeletal muscle, the ocular lens, or the brain. SIGNIFICANCE: The results provide a set of markers that can be used to trace the process of normal tissue aging in medaka and to evaluate the effect of environmental stressors

Cancer survivorship practices, services and delivery: A report from the Children’s Oncology Group (COG) nursing discipline, adolescent/young adult, and late effects committee

Abstract Purpose To describe survivorship services provided by the Children's Oncology Group (COG), an assessment of services was undertaken. Our overall aims were (1) to describe survivorship services, including the extent of services provided, resources (personnel, philanthropy, and research funding), billing practices, and barriers to care and 2) to describe models of care that are in use for childhood cancer survivors and adult survivors of childhood cancer. Methods One hundred seventy-nine of 220 COG institutions (81%) completed an Internet survey in 2007. Results One hundred fifty-five (87%) reported providing survivorship care. Fifty-nine percent of institutions provide care for their pediatric population in specialized late effects programs. For adult survivors, 47% of institutions chose models of care, which included transitioning to adult providers for risk-based health care, while 44% of institutions keep survivors indefinitely at the treating institution (Cancer Center Based Model without Community Referral). Sixty-eight percent provide survivors with a copy of their survivorship care plan. Only 31% of institutions provide a detailed summary of results after each clinic visit, and 41% have a database to track survivor health outcomes. Minimal time required for initial and annual survivorship visits is estimated to be approximately 120 and 90 min, respectively. The most prevalent barriers to care were the lack of dedicated time for program development and a perceived insufficient knowledge on the part of the clinician receiving the transition referral

Health Status of Adult Long-term Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study

Context: Adult survivors of childhood cancer are at risk for medical and psychosocial sequelae that may adversely affect their health status. Objectives: To compare the health status of adult survivors of childhood cancer and siblings and to identify factors associated with adverse outcomes. Design, Setting, and Participants: Health status was assessed in 9535 adult participants of the Childhood Cancer Survivor Study, a cohort of long-term survivors of childhood cancer who were diagnosed between 1970 and 1986. A randomly selected cohort of the survivors\u27 siblings (n=2916) served as a comparison group. Main Outcome Measures: Six health status domains were assessed: general health, mental health, functional status, activity limitations, cancer-related pain, and cancer-related anxiety/fears. The first 4 domains were assessed in the control group. Results: Survivors were significantly more likely to report adverse general health (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-3.0; P\u3c.001), mental health (OR, 1.8; 95% CI, 1.6-2.1; P\u3c.001), activity limitations (OR, 2.7; 95% CI, 2.3-3.3; P\u3c.001), and functional impairment (OR, 5.2; 95% CI, 4.1-6.6; P\u3c.001), compared with sibiings. Forty-four percent of survivors reported at least 1 adversely affected health status domain. Sociodemographic factors associated with reporting at least 1 adverse health status domain included being female (OR, 1.4; 95% CI, 1.3-1.6; P\u3c.001), lower level of educational attainment (OR, 2.0; 95% CI, 1.8-2.2; P\u3c.001), and annual income less than $20000 (OR, 1.8; 95% CI, 1.6-2.1; P\u3c.001). Relative to those survivors with childhood leukemia, an increased risk was observed for at least 1 adverse health status domain among those with bone tumors (OR, 2.1; 95% CI, 1.8-2.5; P\u3c.001), central nervous system tumors (OR, 1.7; 95% CI, 1.5-2.0; P\u3c.001), and sarcomas (OR, 1.2; 95% CI, 1.1-1.5; P=.01). Conclusion: Clinicians caring for adult survivors of childhood cancer should be aware of the substantial risk for adverse health status, especially among females, those with low educational attainment, and those with low household incomes

Stakeholder validation of a model of readiness for transition to adult care

IMPORTANCE: That too few youth with special health care needs make the transition to adult-oriented health care successfully may be due, in part, to lack of readiness to transfer care. There is a lack of theoretical models to guide development and implementation of evidence-based guidelines, assessments, and interventions to improve transition readiness. OBJECTIVE: To further validate the Social-ecological Model of Adolescent and Young Adult Readiness to Transition (SMART) via feedback from stakeholders (patients, parents, and providers) from a medically diverse population in need of life-long follow-up care, survivors of childhood cancer. DESIGN: Mixed-methods participatory research design. SETTING: A large Mid-Atlantic children's hospital. PARTICIPANTS: Adolescent and young adult survivors of childhood cancer (n = 14), parents (n = 18), and pediatric providers (n = 10). MAIN EXPOSURES: Patients and parents participated in focus groups; providers participated in individual semi-structured interviews. MAIN OUTCOMES AND MEASURES: Validity of SMART was assessed 3 ways: (1) ratings on importance of SMART components for transition readiness using a 5-point scale (0-4; ratings >2 support validity), (2) nominations of 3 “most important” components, and (3) directed content analysis of focus group/interview transcripts. RESULTS: Qualitative data supported the validity of SMART, with minor modifications to definitions of components. Quantitative ratings met criteria for validity; stakeholders endorsed all components of SMART as important for transition. No additional SMART variables were suggested by stakeholders and the “most important” components varied by stakeholders, thus supporting the comprehensiveness of SMART and need to involve multiple perspectives. CONCLUSIONS AND RELEVANCE: SMART represents a comprehensive and empirically validated framework for transition research and program planning, supported by survivors of childhood cancer, parents, and pediatric providers. Future research should validate SMART among other populations with special health care needs

Minority Adult Survivors of Childhood Cancer: A Comparison of Long-Term Outcomes, Health Care Utilization, and Health-Related Behaviors From the Childhood Cancer Survivor Study

PURPOSE: To determine the influence of race/ethnicity on outcomes in the Childhood Cancer Survivor Study (CCSS). PATIENTS AND METHODS: Of CCSS adult survivors in the United States, 443 (4.9%) were black, 503 (5.6%) were Hispanic and 7,821 (86.6%) were white. Mean age at interview, 26.9 years (range, 18 to 48 years); mean follow-up, 17.2 years (range, 8.7 to 28.4 years). Late mortality, second malignancy (SMN) rates, health care utilization, and health status and behaviors were assessed for blacks and Hispanics and compared with white survivors. RESULTS: Late mortality rate (6.5%) and 15-year cumulative incidence of SMN (3.5%) were similar across racial/ethnic groups. Minority survivors were more likely to have lower socioeconomic status (SES); final models were adjusted for income, education, and health insurance. Although overall health status was similar, black survivors were less likely to report adverse mental health (females: odds ratio [OR], 0.6; 95% CI, 0.4 to 0.9; males: OR, 0.5; 95% CI, 0.3 to 0.8). Differences in health care utilization and behaviors noted: Hispanic survivors were more likely to report a cancer center visit (females: OR, 1.5; 95% CI, 1.1 to 2.0; males: OR, 1.7; 95% CI, 1.2 to 2.3); black females were more likely (OR, 1.6; 95% CI, 1.1 to 2.4), and Hispanic females less likely to have a recent Pap smear (OR, 0.7; 95% CI, 0.5 to 1.0); black and Hispanic survivors were less likely to report smoking; black survivors were less likely to report problem drinking. CONCLUSION: Adjusted for SES, adverse outcomes in CCSS were not associated with minority status. Importantly, black survivors reported less risky behaviors and better preventive practices. Hispanic survivors had equitable access to cancer related care