Nuclear gene silencing directs reception of long-distance mRNA silencing in Arabidopsis.

In plants, silencing of mRNA can be transmitted from cell to cell and also over longer distances from roots to shoots. To investigate the long-distance mechanism, WT and mutant shoots were grafted onto roots silenced for an mRNA. We show that three genes involved in a chromatin silencing pathway, NRPD1a encoding RNA polymerase IVa, RNA-dependent RNA polymerase 2 (RDR2), and DICER-like 3 (DCL3), are required for reception of long-distance mRNA silencing in the shoot. A mutant representing a fourth gene in the pathway, argonaute4 (ago4), was also partially compromised in the reception of silencing. This pathway produces 24-nt siRNAs and resulted in decapped RNA, a known substrate for amplification of dsRNA by RDR6. Activation of silencing in grafted shoots depended on RDR6, but no 24-nt siRNAs were detected in mutant rdr6 shoots, indicating that RDR6 also plays a role in initial signal perception. After amplification of decapped transcripts, DCL4 and DCL2 act hierarchically as they do in antiviral resistance to produce 21- and 22-nt siRNAs, respectively, and these guide mRNA degradation. Several dcl genotypes were also tested for their capacity to transmit the mobile silencing signal from the rootstock. dcl1-8 and a dcl2 dcl3 dcl4 triple mutant are compromised in micro-RNA and siRNA biogenesis, respectively, but were unaffected in signal transmission.

Type 2 diabetes in children and adolescents: an emerging disease.

The incidence of type 2 diabetes is increasing in the United States, and minority populations in particular seem to be affected. In the past, it was thought that type 2 diabetes occurred only in adults. However, an alarming epidemic has emerged, and children as young as 8 years of age are now being diagnosed with the disease. The purpose of this article is to present pediatric nurse practitioners with the most recent information about type 2 diabetes in children and adolescents, summarize current understanding about diagnosis, and outline treatment options.

Cost analysis: concepts and application.

Public health nurses are increasingly called upon to justify the cost of care or to decide which of two alternative programs is more cost-effective. Cost studies can be complex and difficult to conduct, but an understanding of the basic techniques allows nurses to fully participate in planning, implementing, and evaluating programs that greatly impact the health of the community. This article defines some of the basic terms used in health economics, discusses standard methods of cost analysis, and provides an example of neonatal screening to illustrate methods of describing, measuring, and assigning a value to cost items.

Methodological issues in newborn screening evaluation with special reference to congenital adrenal hyperplasia.

Evidence-based evaluation of newborn screening is essential because of the increasing number of genetic tests, the mandatory nature of newborn screening in the United States, and the growing cost to the public to maintain expensive screening programs. This paper discusses the methodological problems that arise when applying universally accepted criteria to disorders such as congenital adrenal hyperplasia. These problems include the tendency of screening to alter the natural history of the disease, the lack of consensus about terms and definitions, and the paucity of longitudinal studies on screen detected neonates. In order to evaluate and compare candidate screens we recommend formal national trials of promising programs, with defined responsibility of state agencies, physicians, patients, and insurers for data submission and analysis.

Effect of newborn screening for congenital adrenal hyperplasia.

OBJECTIVE: To compare the incidence of diagnosis and morbidity in newborns who were screened with newborns who were not screened for congenital adrenal hyperplasia (CAH). DESIGN: A retrospective cohort study. SETTING: Arkansas, Oklahoma, and Texas. PATIENTS: An unscreened population in Arkansas and Oklahoma (n = 400118) was compared with a screened population in Texas (n = 1613378) during a 5-year period. Simultaneous data were collected on the incidence of diagnosis and associated morbidity in patients with CAH. MAIN OUTCOME MEASURES: Diagnosis of CAH, age (in days) at diagnosis, and frequency and length of initial hospitalization. RESULTS: The incidence of diagnosis of classic CAH per 100000 newborns in the unscreened cohort (5.75) and in the screened cohort (6.26) was similar (relative risk, 0.92; 95% confidence interval, 0.58-1.44). The unscreened group had 0.73 fewer male newborns with salt-wasting CAH diagnosed per 100000 newborns (relative risk, 0.73; 95% confidence interval, 0.35-1.56). The median age at diagnosis was 26 days for male newborns with salt-wasting CAH in the unscreened cohort vs 12 days in the screened cohort (z = 2.49; P = .01). Male newborns with simple-virilizing CAH and newborns with nonclassic CAH were detected only in the screened cohort. CONCLUSIONS: There was not a statistically significant (P = .73) increase in the diagnosis of salt-wasting CAH in the screened cohort. Male newborns benefited as a result of significantly (P = .01) earlier diagnosis, reduced morbidity, and shorter lengths of hospitalization. Large collaborative studies or meta-analyses are needed to determine the life-saving benefits of screening.

A comparative cost analysis of newborn screening for classic congenital adrenal hyperplasia in Texas.

OBJECTIVE: Texas mandates a two-test newborn screening program for congenital adrenal hyperplasia (CAH): one test at birth and a second test at approximately one to two weeks after birth. The authors compared the dollar cost of detecting infants with CAH clinically and through the screening program. METHODS: The authors estimated the costs of screening newborns in 1994 for CAH, including resources used by the Texas Department of Health and the broader cost to society. RESULTS: Fifteen infants with classic CAH were diagnosed in Texas in 1994 among 325,521 infants born (1:21,701 cumulative incidence). Seven infants were detected clinically and the others were detected through screening, six on the first screen and two on the second screen. The first screen identified all previously undetected infants with severe salt-wasting CAH. The cumulative cost to diagnose the seven infants detected clinically was $79,187. The incremental costs for the screening program were $115,169 per additional infant diagnosed through the first screen and $242,865 per additional infant diagnosed through the second screen. CONCLUSIONS: If the goal is early diagnosis of infants with the severe salt-wasting form of CAH, a single screen is effective. If the goal is to detect infants with the simple virilizing form of the disorder who may benefit from early treatment, the second screen is necessary, but it is not as cost-effective as the first screen.