Frequency and outcome of cervical cancer prevention failures in the United States

We measured the frequency and outcome of cervical cancer prevention failures that occurred in the Papanicolaou (Pap) and colposcopy testing phases involving 1,646,580 Pap tests in 4 American hospital systems between January 1, 1998, and December 31, 2004. We defined a screening failure as a 2-step or greater discordant Pap test result and follow-up biopsy diagnosis. A total of 5,278 failures were detected (0.321% of all Pap tests); 48% and 52% of failures occurred in the Pap test and colposcopy phases, respectively. Missed squamous cancers (1 in 187,786 Pap tests), glandular cancers (1 in 19,426 Pap tests), and high-grade lesions (1 in 6,870 Pap tests) constituted 4.1% of all failures. Unnecessary repeated tests or diagnostic delays occurred in 70.8% and 63.9% of failures involving high- and low-grade lesions, respectively. We conclude that cervical cancer prevention practices are remarkably successful in preventing squamous cancers, although a high frequency of failures results in low-impact negative outcomes.     

Breed relationships facilitate fine-mapping studies: a 7.8-kb deletion cosegregates with Collie eye anomaly across multiple dog breeds

The features of modern dog breeds that increase the ease of mapping common diseases, such as reduced heterogeneity and extensive linkage disequilibrium, may also increase the difficulty associated with fine mapping and identifying causative mutations. One way to address this problem is by combining data from multiple breeds segregating the same trait after initial linkage has been determined. The multibreed approach increases the number of potentially informative recombination events and reduces the size of the critical haplotype by taking advantage of shortened linkage disequilibrium distances found across breeds. In order to identify breeds that likely share a trait inherited from the same ancestral source, we have used cluster analysis to divide 132 breeds of dog into five primary breed groups. We then use the multibreed approach to fine-map Collie eye anomaly (cea), a complex disorder of ocular development that was initially mapped to a 3.9-cM region on canine chromosome 37. Combined genotypes from affected individuals from four breeds of a single breed group significantly narrowed the candidate gene region to a 103-kb interval spanning only four genes. Sequence analysis revealed that all affected dogs share a homozygous deletion of 7.8 kb in the NHEJ1 gene. This intronic deletion spans a highly conserved binding domain to which several developmentally important proteins bind. This work both establishes that the primary cea mutation arose as a single disease allele in a common ancestor of herding breeds as well as highlights the value of comparative population analysis for refining regions of linkage.     

Impacts of a School‐Wide,Peer‐Led Approach to Sexuality Education: A Matched Comparison Group Design

BACKGROUND

Teen Prevention Education Program (PEP) is a school‐wide, peer‐led comprehensive sexuality education program currently implemented in more than 50 schools across 2 states. Many teen pregnancy prevention researchers and practitioners view peer‐led programs as a promising approach for reducing teen pregnancy and associated sexual risk behaviors. However, prior research on the effectiveness of these programs indicates mixed results.

METHODS

We randomly assigned schools to implement Teen PEP immediately (intervention group) or on a delayed schedule (comparison group) and used propensity score matching to improve the comparability of the study groups. We surveyed students at baseline and about 6 months after the program ended.

RESULTS

Teen PEP did not significantly impact rates of sexual activity or unprotected sex; however, the program led to improvements in exposure to information about sexual health topics and knowledge of preventing pregnancy and transmission of sexually transmitted infections.

CONCLUSIONS

Teen PEP succeeded in accomplishing some of its most proximal goals, increasing students' access to information and knowledge. However, we found little evidence that the program affects sexual risk‐taking within 6 months of its conclusion. Future research will examine the program's longer‐term impacts on sexual risk behaviors.

     

Differentiation of neural stem cells into cells of oligodendroglial lineage

We described three different conditions that induce differentiation of dissociated neural stem cells derived from mouse embryonic CNS. In the first set of experiments, where the cell differentiation was triggered by cell adhesion, removal of growth factors and serum-supplemented medium, only sporadic neuronal and astroglial cells survived longer than two weeks and the latter formed a monolayer. When differentiation was induced in serum-free medium supplemented with retinoic acid, rapid and massive cell death occurred. A prolonged survival was observed in cultivation medium supplemented with serum and growth factors EGF plus FGF-2. One third of the cells did not express cell differentiation markers and were responsible for an increase in cell numbers. The remaining cells differentiated and formed the astrocytic monolayer on which occasional neuronal cells grew. One third of the differentiated phenotypes were represented by cells of oligodendroglial lineage. Differentiation of oligodendroglial cells occurred in a stepwise mechanism because the culture contained all successive developmental stages, including oligodendrocyte progenitors, preoligodendrocytes and immature and mature oligodendrocytes. Maturing oligodendrocytes displayed immunocytochemical and morphological features characteristic of cells that undergo physiological development. The cultivation conditions that supported growth and differentiation of neural stem cells were optimal for in vitro developmental studies and the production of oligodendroglial cells.     

Real-time PCR diagnostics failure caused by nucleotide variability within exon 4 of the human cytomegalovirus major immediate-early gene

Here we report how variability in the human cytomegalovirus genome sequence may seriously affect the outcome of its molecular diagnosis. A real-time quantitative PCR assay targeting the major immediate-early gene failed to detect the viral load in some, but not all, clinical samples from hematooncological patients. By amplification and sequencing the DNA across the regions targeted by this assay we found a number of nucleotide substitutions which accounted for decreased primer/probe binding. This decreased the sensitivity of the assay up to 1,000-fold.     

Isoflavones--safe food additives or dangerous drugs?

The sales volume of products containing isoflavone has increased since the publication of the Women's Health Initiative. The many apparently contradictory results published on the effects of isoflavones on a variety of estrogen-regulated organs point to both beneficial as well as adverse effects on human health. It is of particular importance that psychovegetative climacteric complaints such as hot flushes are, if at all, only slightly influenced by isoflavones. The substances appear to have weak anti-osteoporotic effect. Their anti-atherosclerotic action is debatable, as not all authors find any beneficial effect on lipids. Most importantly, there is dispute as to whether isoflavones derived from soy or red clover have negative, positive or any effect at all on the mammary gland or endometrium. It is beyond any doubt that soy products may have cancer preventing properties in a variety of organs including the mammary gland. However, these properties may only be exerted if the developing organ was under the influence of isoflavones during childhood and puberty. This may also explain the often quoted "Japanese Phenomenon", the fact that breast cancer occurs to a lesser extent in Japanese women. When administered to isoflavone "inexperienced" women at the time of menopause, the phytoestrogens appear to share the same effects as estrogen used in classical preparations for hormone replacement therapy, i.e. they may stimulate the proliferation of endometrial and mammary gland tissue with at present unknown and unpredictable risk to these organs. Therefore, the following question arises for the clinician: Why should soy or red clover products containing isoflavone be recommended, if the positive effects are only negligible but the adverse effects serious?     

Utility of urinary 1-naphthol and 2-naphthol levels to assess environmental carbaryl and naphthalene exposure in an epidemiology study

We recently reported associations between urinary 1-naphthol (1N) levels and several intermediate measures of male reproductive health, namely sperm motility, serum testosterone levels, and sperm DNA damage. However, because 1N is a major urinary metabolite of both naphthalene and the insecticide carbaryl, exposure misclassification stemming from differences in exposure source was probable and interpretation of the results was limited. As naphthalene, but not carbaryl, is also metabolized to 2-naphthol (2N), the relationship of urinary 1N to 2N within an individual may give information about source of 1N. Utilizing data from two previous studies that measured both 1N and 2N in urine of men exposed to either carbaryl or naphthalene, the present study employed several methods to differentiate urinary 1N arising from exposures to carbaryl and naphthalene among men in the reproductive health study. When re-evaluating the reproductive health data, techniques for identifying 1N source involved exploring interaction terms, stratifying the data set based on 1N/2N ratios, and performing an exposure calibration using a linear 1N to 2N relationship from a study of workers exposed to naphthalene in jet fuel. Despite some inconsistencies between the methods used to distinguish 1N source, we found that 1N from carbaryl exposure is likely responsible for the previously observed association between 1N and sperm motility, whereas 1N from naphthalene exposure is likely accountable for the association between 1N and sperm DNA damage. We demonstrate that studies of health effects associated with carbaryl should utilize a 1N/2N ratio to identify subgroups in which carbaryl is the primary source of 1N. Conversely, studies of naphthalene-related outcomes may utilize 2N levels to estimate exposure.