Cancer survivor rehabilitation and recovery: Protocol for the Veterans Cancer Rehabilitation Study (Vet-CaRes)

Background: Cancer survivors are a rapidly growing and aging population in the U.S., but there are many challenges associated with the survivorship experience such as functional disabilities and psychosocial distress. When viewed next to the general population, Veterans are especially at risk for these challenges as they are older and have a high incidence of co-morbid conditions. While the Institute of Medicine (IOM) has called for further cancer survivorship research to address these challenges, we still know little about this experience from the perspective of aging Veterans. Methods/design We conducted a longitudinal, mixed-methods study over the course of three and a half years at the Boston and Houston VA Medical Centers. We recruited 170 Veterans diagnosed with head and neck, colorectal and esophageal/gastric cancers that were identified from the VA tumor registry. Veterans completed three in-depth interviews, conducted at 6, 12 and 18 months after pathology confirmation, measuring the physical, social and psychological factors related to cancer survivorship. The longitudinal design allowed us to assess any changes in cancer related disability and distress over time. Discussion Weekly teleconference study team meetings were a key aspect to the research process. Issues related to recruitment, data management and analysis, and the dissemination of research results was discussed. Interviewers presented detailed case reports of completed interviews that allowed us to refine our interview protocols. We also discussed issues relevant to the Veteran population of which we were previously unaware and some of the challenges of the research process itself. This novel study produced a robust data set that documents the functional and psychosocial cancer survivorship experiences of aging Veterans. The longitudinal design will help us more fully understand the recovery patterns for this specific population, and identify the unique needs and gaps in health services

A controlled trial of Partners in Dementia Care: veteran outcomes after six and twelve months

Introduction: “Partners in Dementia Care” (PDC) tested the effectiveness of a care-coordination program integrating healthcare and community services and supporting veterans with dementia and their caregivers. Delivered via partnerships between Veterans Affairs medical centers and Alzheimer’s Association chapters, PDC targeted both patients and caregivers, distinguishing it from many non-pharmacological interventions. Hypotheses posited PDC would improve five veteran self-reported outcomes: 1) unmet need, 2) embarrassment about memory problems, 3) isolation, 4) relationship strain and 5) depression. Greater impact was expected for more impaired veterans. A unique feature was self-reported research data collected from veterans with dementia. Methods and Findings: Five matched communities were study sites. Two randomly selected sites received PDC for 12 months; comparison sites received usual care. Three structured telephone interviews were completed every 6 months with veterans who could participate. Results: Of 508 consenting veterans, 333 (65.6%) completed baseline interviews. Among those who completed baseline interviews, 263 (79.0%) completed 6-month follow-ups and 194 (58.3%) completed 12-month follow-ups. Regression analyses showed PDC veterans had significantly less adverse outcomes than those receiving usual care, particularly for more impaired veterans after 6 months, including reduced relationship strain (B = −0.09; p = 0.05), depression (B = −0.10; p = 0.03), and unmet need (B = −0.28; p = 0.02; and B = −0.52; p = 0.08). PDC veterans also had less embarrassment about memory problems (B = −0.24; p = 0.08). At 12 months, more impaired veterans had further reductions in unmet need (B = −0.96; p < 0.01) and embarrassment (B = −0.05; p = 0.02). Limitations included use of matched comparison sites rather than within-site randomization and lack of consideration for variation within the PDC group in amounts and types of assistance provided. Conclusions: Partnerships between community and health organizations have the potential to meet the dementia-related needs and improve the psychosocial functioning of persons with dementia. Trial Registry NCT0029116

Exploring the associations between microRNA expression profiles and environmental pollutants in human placenta from the National Children's Study (NCS)

The placenta is the principal regulator of the in utero environment, and disruptions to this environment can result in adverse offspring health outcomes. To better characterize the impact of in utero perturbations, we assessed the influence of known environmental pollutants on the expression of microRNA (miRNA) in placental samples collected from the National Children's Study (NCS) Vanguard birth cohort. This study analyzed the expression of 654 miRNAs in 110 term placentas. Environmental pollutants measured in these placentas included dichlorodiphenyldichloroethylene (DDE), bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd). A moderated t-test was used to identify a panel of differentially expressed miRNAs, which were further analyzed using generalized linear models. We observed 112 miRNAs consistently expressed in >70% of the samples. Consistent with the literature, miRNAs located within the imprinted placenta-specific C19MC cluster, specifically mir-517a, mir-517c, mir-522, and mir-23a, are among the top expressed miRNA in our study. We observed a positive association between PBDE 209 and miR-188–5p and an inverse association between PBDE 99 and let-7c. Both PCBs and Cd were positively associated with miR-1537 expression level. In addition, multiple let-7 family members were downregulated with increasing levels of Hg and Pb. We did not observe DDE or BPA levels to be associated with placental miRNA expression. This is the first birth cohort study linking environmental pollutants and placental expression of miRNAs. Our results suggest that placental miRNA profiles may signal in utero exposures to environmental chemicals

Evidence for the Bifunctional Nature of Mitochondrial Phosphatidylserine Decarboxylase: Role in Pdr3-Dependent Retrograde Regulation of PDR5 Expression▿

Multidrug resistance in the yeast Saccharomyces cerevisiae is sensitive to the mitochondrial genome status of cells. Cells that lose their organellar genome ([rho0] cells) dramatically induce transcription of multiple or pleiotropic drug resistance genes via increased expression of a zinc cluster-containing transcription factor designated Pdr3. A major Pdr3 target gene is the ATP-binding cassette transporter-encoding gene PDR5. Pdr5 has been demonstrated to act as a phospholipid floppase catalyzing the net outward movement of phosphatidylethanolamine (PE). Since the mitochondrially localized Psd1 enzyme provides a major route of PE biosynthesis, we evaluated the potential linkage between Psd1 function and PDR5 regulation. Overproduction of Psd1 in wild-type ([rho+]) cells was found to induce PDR5 transcription and drug resistance in a Pdr3-dependent manner. Loss of the PSD1 gene from [rho0] cells prevented the normal activation of PDR5 expression. Surprisingly, expression of a catalytically inactive form of Psd1 still supported PDR5 transcriptional activation, suggesting that PE levels were not the signal triggering PDR5 induction. Expression of green fluorescent protein fusions mapped the region required to induce PDR5 expression to the noncatalytic amino-terminal portion of Psd1. Psd1 is a novel bifunctional protein required both for PE biosynthesis and regulation of multidrug resistance

Come, Join, Lead: Attracting Students to Careers in Aging and Promoting Involvement in Gerontological Societies

Geriatric educators face the challenge of attracting more clinicians, scientists, and educators into geriatrics and gerontology, and promoting involvement in gerontological societies. A survey of psychologists (N = 100) examined factors that attract students in clinical/counseling psychology to practice with older adults, as well as experiences in organizational service. For 58%, interest in aging began at the undergraduate level, but for others interest developed later. About one half cited academic exposure such as mentorship (51%), research (47%), or coursework (45%) as sparking interest, along with family (68%) or work experience (61%). Involvement in professional organizations lags (58%), in part owing to misperceptions about what those activities require. A continued targeted effort at the undergraduate and graduate level is essential to attract students to careers in aging. To preserve vital professional organizations, enhanced outreach may be useful to dispel myths about service and encourage engagement

Sleep Continuity, Sleep Related Daytime Dysfunction, and Problem Endorsement: Do These Vary Concordantly by Age?

OBJECTIVES: Sleep continuity (i.e., ability to initiate and/or maintain sleep) worsens with age. It is unclear whether problem endorsement and/or daytime dysfunction show similar age-related trends. Accordingly, a large archival dataset was used to examine age differences in sleep continuity, problem endorsement, and sleep related daytime dysfunction. METHOD: Participants were categorized as: Young Adults (18-29 years); Adults (30-44 years); Middle Aged Adults (45-64 years); and Older Adults (65-89 years). Young Adults, Adults, and Middle Aged Adults were 1:1 matched with Older Adults (n = 233) on the basis of gender, race, ethnicity, and BMI. MANOVA, ANOVAs, and chi-square analysis were performed to assess for age-related differences. RESULTS: In a sample of 932 adults with self-reported sleep continuity disturbance (i.e., insomnia), sleep continuity was significantly worse in older age groups. This effect was limited to middle and late insomnia with middle aged and older adults waking up with greater frequency and for longer durations of time during the night and in the early morning than younger cohorts. Problem endorsement largely increased across age groups (except for sleep latency) but reports of overall sleep-related daytime dysfunction showed no difference by age. CONCLUSION: When evaluating sleep continuity disturbance, assessing whether the patient identifies their sleep continuity disturbance as a problem and whether it affects their daytime function can be informative, particularly in older adults. It may serve to reveal (case-by-case) when there are discordances between incidence/severity of illness and problem endorsement/daytime dysfunction. Such information may better inform if treatment should be initiated