Deletion of the distal short arm of chromosome 9 (9p) has been reported in a number of cases to be associated with gonadal dysgenesis and XY sex reversal, suggesting that this region contains one or more genes required in two copies for normal testis development. Recent studies have greatly narrowed the interval containing this putative autosomal testis-determining gene(s) to the distal portion of 9p24.3. We previously identified DMRT1, a human gene with sequence similarity to genes that regulate the sexual development of nematodes and insects. These genes contain a novel DNA-binding domain, which we named the DM domain. DMRT1 maps to 9p24. 3 and in adults is expressed specifically in the testis. We have investigated the possible role of DM domain genes in 9p sex reversal. We identified a second DM domain gene, DMRT2, which also maps to 9p24.3. We found that point mutations in the coding region of DMRT1 and the DM domain of DMRT2 are not frequent in XY females. We showed by fluorescence in situ hybridization analysis that both genes are deleted in the smallest reported sex-reversing 9p deletion, suggesting that gonadal dysgenesis in 9p-deleted individuals might be due to combined hemizygosity of DMRT1 and DMRT2.

Our results suggest that greater concordance with DASH guidelines did not have an independent long-term association with hypertension or cardiovascular mortality in this cohort. This implies that very high concordance, as achieved in the DASH trials, may be necessary to achieve any benefits of the DASH diet.

Replication-associated histone genes encode the only metazoan mRNAs that lack polyA tails, ending instead in a conserved 26-nt sequence that forms a stem-loop. Most of the regulation of mammalian histone mRNA is posttranscriptional and mediated by this unique 3 end. Stem-loop-binding protein (SLBP) binds to the histone mRNA 3 end and is thought to participate in all aspects of histone mRNA metabolism, including cell cycle regulation. To examine SLBP function genetically, we have cloned the gene encoding Drosophila SLBP (dSLBP) by a yeast three-hybrid method and have isolated mutations in dSLBP. dSLBP function is required both zygotically and maternally. Strong dSLBP alleles cause zygotic lethality late in development and result in production of stable histone mRNA that accumulates in nonreplicating cells. These histone mRNAs are cytoplasmic and have polyadenylated 3 ends like other polymerase II transcripts. Hypomorphic dSLBP alleles support zygotic development but cause female sterility. Eggs from these females contain dramatically reduced levels of histone mRNA, and mutant embryos are not able to complete the syncytial embryonic cycles. This is in part because of a failure of chromosome condensation at mitosis that blocks normal anaphase. These data demonstrate that dSLBP is required in vivo for 3 end processing of histone pre-mRNA, and that this is an essential function for development. Moreover, dSLBP-dependent processing plays an important role in coupling histone mRNA production with the cell cycle.

Immunizations are crucial to the prevention of disease, thus, having an accurate measure of vaccination status for a population is an important guide in targeting prevention efforts. In order to comprehensively assess the validity of self-reported adult vaccination status for the eight most common adult vaccines we conducted a survey of vaccination receipt and compared it to the electronic medical record (EMR), which was used as the criterion standard, in a population of community-dwelling patients in a large healthcare system. In addition, we assessed whether validity varied by demographic factors. The vaccines included: pneumococcal (PPSV), influenza (Flu), tetanus diphtheria (Td), tetanus diphtheria pertussis (Tdap), Human PapillomaVirus (HPV), hepatitis A (HepA), hepatitis B (HepB) and herpes zoster (shingles). Telephone surveys were conducted with 11,760 individuals, ≥ 18, half with documented receipt of vaccination and half without. We measured sensitivity, specificity, positive and negative predictive value, net bias and over-and under-reporting of vaccination. Variation was found across vaccines, however, sensitivity and specificity did not vary substantially by either age or race/ethnicity. Sensitivity ranged between 63% for HepA to over 90% (tetanus, HPV, shingles and Flu). Hispanics were 2.7 times more likely to claim receipt of vaccination compared to whites. For PPSV and Flu those 65+ had low specificity compared to patients of younger ages while those in the youngest age group had lowest specificity for HepA and HepB. In addition to racial/ethnic differences, over-reporting was more frequent in those retired and those with household income less than $75,000. Accurate information for vaccination surveillance is important to estimate progress toward vaccination

The prevalence of hypertension in this community-based study is lower than previously reported from school-based studies. With the size and diversity of this cohort, these results suggest the prevalence of hypertension in children may actually be lower than previously reported.

PURPOSE Many clinical preventive care services are recommended for adolescents. Little is known about whether most adolescents have a suffi cient number of preventive care services visits over time to receive those services. We wanted to measure how frequently adolescents who are insured either through private insurance or government programs have preventive vs nonpreventive care visits. METHODSWe conducted a retrospective descriptive analysis based on claims data from a large health plan in Minnesota with about 700,000 members. All study patients were aged 11 to 18 years between January 1, 1998, and December 31, 2007. Our outcome measure was rates of preventive and nonpreventive care visits.RESULTS One-third of adolescents with 4 or more years of continuous enrollment had no preventive care visits from age 13 through 17 years, and another 40% had only a single such visit. Nonpreventive care visits were more frequent in all age-groups, averaging about 1 per year at age 11 years, climbing to about 1.5 per year at age 17 years. Differences in rates between government insurance and commercial insurance were small. In older adolescence, girls had more preventive care visits and more nonpreventive care visits than did boys.CONCLUSIONS Most adolescents come in infrequently for preventive care visits but more often for nonpreventive care visits. We recommend using the same approach in adolescence for preventive care that is being used in adults: the nomissed-opportunities paradigm. All visits by adolescents should be viewed as an opportunity to provide preventive care services, and systems should be set up to make that possible, even in busy practices with short encounters with a clinician.

OBJECTIVE:To examine the association of voluntary vs involuntary weight loss with incidence of cancer in older women. DESIGN: Prospective cohort study from 1993 to 2000, with cancer incidence identified through record linkage to a cancer registry. SUBJECTS: A total of 21 707 postmenopausal women initially free of cancer. MESUREMENTS: Women completed a questionnaire about intentional and unintentional weight loss episodes of Z20 pounds during adulthood. RESULTS: Compared with women who never had any Z20 pounds weight loss episode, women who ever experienced intentional weight loss Z20 pounds but no unintentional weight loss had incidence rates lower by 11% for any cancer (RR ¼ 0.89, 95% CI 0.79-1.00), by 19% for breast cancer (RR ¼ 0.81, 95% CI 0.66-1.00), by 9% for colon cancer (RR ¼ 0.91, 95% CI 0.66-1.24), by 4% for endometrial cancer (RR ¼ 0.96, 95% CI 0.61-1.52), and by 14% for all obesity-related cancer (RR ¼ 0.86, 95% CI 0.74-1.01) after adjusting for age, body mass index, waist-to-hip ratio, physical activity, education, marital status, smoking status, pack-years of cigarettes, current estrogen use, alcohol use, parity, and multivitamin use. Furthermore, although overweight women were at increased risk of several cancers, women who experienced intentional weight loss episodes of 20 or more pounds and were not currently overweight were observed to have an incidence of cancer similar to nonoverweight women who never lost weight. Unintentional weight loss episodes were not associated with decreased cancer risk. CONCLUSIONS: These findings suggest that intentional weight loss might reduce risk of obesity-related cancers.

PURPOSE We sought to examine the association of food security and metabolic syndrome in a representative sample of U.S. adults and adolescents. We hypothesized that compared with those in food-secure households, adolescents and adults living in food-insecure households would have increased odds of (MetS). METHODS Data from the National Health and Nutrition Examination Surveys from 1999 to 2006 were combined and analyzed cross-sectionally. Logistic regression was used to compute odds ratios and 95% confidence intervals (95% CI) in the association of household food security (fully food secure, marginal, low, and very low food security) and MetS. RESULTS Compared with those who were food secure, adults in households with marginal food security had 1.80-fold increased odds of MetS (95% CI, 1.30–2.49), and those with very low food security had a 1.65-fold increased odds of MetS (95% CI 1.12–2.42). There was no association with low food security. The association of marginal household food security and MetS was not significant in adolescents. In adults and adolescents, very low was food security not associated with increased odds of MetS compared with those who were food secure. CONCLUSIONS Members of households with marginal and very low food security are at increased risk of MetS. A mechanism may be that foods that are inexpensive and easily accessible tend to be energy dense and nutrient poor.