The increasing availability of personal genomic tests has led to discussions about the validity and utility of such tests and the balance of benefits and harms. A multidisciplinary workshop was convened by the National Institutes of Health and the Centers for Disease Control and Prevention to review the scientific foundation for using personal genomics in risk assessment and disease prevention and to develop recommendations for targeted research. The clinical validity and utility of personal genomics is a moving target with rapidly developing discoveries but little translation research to close the gap between discoveries and health impact. Workshop participants made recommendations in five domains: (1) developing and applying scientific standards for assessing personal genomic tests; (2) developing and applying a multidisciplinary research agenda, including observational studies and clinical trials to fill knowledge gaps in clinical validity and utility; (3) enhancing credible knowledge synthesis and information dissemination to clinicians and consumers; (4) linking scientific findings to evidence-based recommendations for use of personal genomics; and (5) assessing how the concept of personal utility can affect health benefits, costs, and risks by developing appropriate metrics for evaluation. To fulfill the promise of personal genomics, a rigorous multidisciplinary research agenda is needed.

Background

Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies. Its rapid onset and resistance to conventional therapeutics contribute to a mean survival of six months after diagnosis and make the identification of thyroid-cancer-initiating cells increasingly important.

Methodology/Principal Findings

In prior studies of ATC cell lines, CD133+ cells exhibited stem-cell-like features such as high proliferation, self-renewal and colony-forming ability in vitro. Here we show that transplantation of CD133+ cells, but not CD133− cells, into immunodeficient NOD/SCID mice is sufficient to induce growth of tumors in vivo. We also describe how the proportion of ATC cells that are CD133+ increases dramatically over three months of culture, from 7% to more than 80% of the total. This CD133+ cell pool can be further separated by flow cytometry into two distinct populations: CD133+/high and CD133+/low. Although both subsets are capable of long-term tumorigenesis, the rapidly proliferating CD133+/high cells are by far the most efficient. They also express high levels of the stem cell antigen Oct4 and the receptor for thyroid stimulating hormone, TSHR. Treating ATC cells with TSH causes a three-fold increase in the numbers of CD133+ cells and elicits a dose-dependent up-regulation of the expression of TSHR and Oct4 in these cells. More importantly, immunohistochemical analysis of tissue specimens from ATC patients indicates that CD133 is highly expressed on tumor cells but not on neighboring normal thyroid cells.

Conclusions/Significance

To our knowledge, this is the first report indicating that CD133+ ATC cells are solely responsible for tumor growth in immunodeficient mice. Our data also give a unique insight into the regulation of CD133 by TSH. These highly tumorigenic CD133+ cells and the activated TSH signaling pathway may be useful targets for future ATC therapies.

Ongoing advances in stem cell research have opened new avenues for therapy for many human disorders. Until recently, however, thyroid stem cells have been relatively understudied. Here, we review what is known about thyroid stem cells and explore their utility as models of normal and malignant biological development. We also discuss the cellular origin of thyroid cancer stem cells and explore the clinical implications of cancer stem cells in the thyroid gland. Since thyroid cancer is the most common form of endocrine cancer and that thyroid hormone is needed for the growth and metabolism of each cell in the body, understanding the molecular and the cellular aspects of thyroid stem cell biology will ultimately provide insights into mechanisms underlying human disease.

OBJECTIVES

To measure the prevalence of fear of falling in older adults at the time of long- term care (LTC) enrollment and identify potentially treatable risk factors for low fall related self-efficacy.

DESIGN

Prospective cohort study.

SETTING

Three LTC programs in Upstate New York.

PARTICIPANTS

112 new enrollees in LTC, aged 55 or older, who passed a cognitive screen.

MEASUREMENTS

Self-reported falls, the falls efficacy scale (FES), medical conditions, the short geriatric depression scale, and physical performance measures (Berg balance scale, hip flexor, knee extensor and grip strength, gait speed and a six-minute walk).

RESULTS

Of the 54 subjects (48.2%) who reported fear of falling, 41 (75.9%) reported activity modification secondary to fear. Fearful subjects were more likely to be female (P=.003), report low back pain (P=.030) and lower extremity arthritis (P=.048). Fearful subjects were weaker at the hip (P<.001) and knee (P=.001), and had shorter six-minute walk distances. Subjects with better FES scores had better Berg scores (P<.001), had greater hip and knee strength, had faster gait speeds and walked further in six minutes (P<.001, P=.006, P=.001 and P=.001 respectively). Subjects with low FES scores and fearful subjects were more likely to have depressive symptoms (P=.003, P=.044, respectively).

CONCLUSION

Falls and fear of falling are more common in new LTC enrollees than in previously described community dwelling and SNF cohorts. Attention to associated characteristics like depression, arthritis, low back pain and lower extremity weakness may identify opportunities to reduce fear and improve patient safety during this transitional period.

Mitochondrial DNA (MtDNA) with a neutral buoyant density of 1.681 g/cm3 has been isolated from unfertilized eggs of Drosophila melanogaster. This DNA is a circular molecule with an average length of 5.3 µm; it reassociates with a low C0t1/2 after denaturation, and in alkaline isopycnic centrifugation it separates into strands differing in density by 0.005 g/cm3. MtDNA isolated from purified mitochondria of unfertilized eggs or from total larval DNA melts with three distinct thermal transitions. The three melting temperature values suggest that the molecule may have three regions differing in average base composition. DNA isolated from unfertilized eggs of D. melanogaster contains approximately equal amounts of MtDNA and another DNA with a buoyant density of 1.697 g/cm3, slightly less dense than main peak DNA. The possibility that the heavier DNA fraction consists of amplified ribosomal DNA was excluded by hybridization experiments, but otherwise nothing is known of its origin or function.