Endogenous small interfering RNAs (endo-siRNAs) have been discovered in many organisms, including mammals. In C. elegans, depletion of germline-enriched endo-siRNAs found in complex with the CSR-1 Argonaute protein causes sterility and defects in chromosome segregation in early embryos. We discovered that knockdown of either csr-1, the RNA-dependent RNA polymerase (RdRP) ego-1, or the dicer-related helicase drh-3, leads to defects in histone mRNA processing, resulting in severe depletion of core histone proteins. The maturation of replication-dependent histone mRNAs, unlike that of other mRNAs, requires processing of their 3'UTRs through an endonucleolytic cleavage guided by the U7 snRNA, which is lacking in C. elegans. We found that CSR-1-bound antisense endo-siRNAs match histone mRNAs and mRNA precursors. Consistently, we demonstrate that CSR-1 directly binds to histone mRNA in an ego-1-dependent manner using biotinylated 2'-O-methyl RNA oligonucleotides. Moreover, we demonstrate that increasing the dosage of histone genes rescues the lethality associated with depletion of CSR-1 and EGO-1. These results support a positive and direct effect of RNAi on histone gene expression.

BACKGROUND AND OBJECTIVES: Current clinical guidelines do not consider patients with rheumatic conditions to be at high risk for celiac disease (CD) despite numerous reported associations between the two in adults and children. The objective of this study was to evaluate the prevalence of CD among patients presenting for pediatric rheumatology evaluation.METHODS: A total of 2125 patients presenting for initial evaluation by the Division of Pediatric Rheumatology at the Hospital for Special Surgery between June 2006 and December 2013 were screened for CD as a part of the standard initial serologic evaluation. The charts of these patients were evaluated retrospectively at the end of this period.RESULTS: 36 patients (30 girls, 6 boys, mean age 9.4 6 4.3 years, range 2-16 years) received a diagnosis of CD after serologic testing and evaluation by pediatric gastroenterology. Eight additional patients with known diagnoses of CD presented during this time period. The total prevalence of CD over this 6.5-year period was 2.0%. The most common presenting complaints among patients diagnosed with CD were myalgias, arthralgias, and rash. Less frequently, patients reported gastrointestinal complaints including abdominal pain, nausea, and diarrhea. All patients reported improvement or complete resolution of their musculoskeletal symptoms after initiation of a gluten-free diet.CONCLUSIONS: This study identified 36 new cases of CD among children presenting for rheumatology evaluation, for an overall prevalence rate of 2.0%. The majority of patients who ultimately received a diagnosis of CD presented with extraintestinal manifestations. These results underscore the importance of screening children presenting for rheumatology evaluation for CD. WHAT'S KNOWN ON THIS SUBJECT:Associations have been reported between celiac disease (CD) and numerous autoimmune conditions in adults and children. However, current screening guidelines do not consider patients with rheumatic diseases to be at high risk for CD. WHAT THIS STUDY ADDS:The prevalence of CD in children presenting for rheumatology evaluation was found to be 2% by routine serologic screening. The majority of screening-detected CD cases had no CD-associated symptoms. Gluten restriction was found to relieve some musculoskeletal complaints.

The neuropsychiatric manifestations of childhood-onset systemic lupus erythematosus (cSLE) range from mild cognitive difficulties to depression to psychosis. Neurocognitive dysfunction affects 30%-60% of cSLE patients, impacting the areas of intelligence, academic achievement, arithmetic, reading comprehension, learning, visual memory, and complex problem solving. [1][2][3] The Pediatric Automated Neuropsychological Assessment Metrics (Ped-ANAM) is validated, but it can take up to 35-55 minutes to administer. 4 The ACR has defined cognitive dysfunction in SLE as one of the 19 neuropsychiatric syndromes of SLE, and recommends a battery of standard tests, which are impractical for clinical use. 5 The Childhood Arthritis and Rheumatology Research Alliance (CARRA)Ad-Hoc Neurocognitive Lupus Committee proposed a series of neuropsychological tests for cSLE, but the battery is time consuming. 6 Neuropsychological tests are also associated with increased cost of test administration, and difficulty in scoring and interpretation.Attention difficulties are under-diagnosed and under-studied, but constitute an important component of cognitive dysfunction, and can impair educational and social functioning, self-esteem, and quality of life. 7 We used the Gordon Diagnostic System (GDS), a brief screening tool for attention deficit, in cSLE outpatients. The GDS is a gamelike assessment device that aids in the diagnosis of attention deficit, especially ADHD, by yielding data about an individual's ability to focus and sustain attention over time. 8 The GDS is brief, portable, easy to use, and can be administered by any trained individual, thus offering a clear advantage over other standardized tests.In this bi-institutional prospective pilot study, approved by respective Institutional Review Boards, we evaluated seven cSLE patients (six female, one male, mean age: 13.0 AE 3.2 years;

Some analyses of child deathsl-5 have been concerned with the effect of adverse social factors; others have specifically considered perinatal,6 I post perinatal8 or infant9 10 mortality, malignant disease,1 3 or accidents.'4-'6 We report a study in which the emphasis was on detailed retrospective investigation of the factors leading up to each death of a child resident in a defined area of London during one 18 month period.In 1978 the mortality rates among infants and children aged 1-14 years in this area (child population under 14 years 58 000) were higher by 48 and 72% respectively than regional and national figures." We did not aim to examine these differences per se, but rather to investigate whether there were any potentially avoidable factors in the chain of events leading up to the deaths. Subjects and methodsWith the following exceptions-9 sudden infant deaths (SIDS) investigated as part of another study;18 all babies dying within 24 hours of delivery; and low birthweight (less than 2500 g) infants dying before discharge from hospital-all children under the age of 14 years resident in one London area health authority who died during an 18 month period were included. Each death was notified by the registrar of births and deaths, and a questionnaire, covering medical and social information and a detailed account of events leading to the child's death, was completed for each child. Data was collected from the records of any hospital where the child had been seen, the general practitioner, the community paediatric services and school, and the coroner, and this was supplemented whenever possible by interviews with involved doctors, health visitors, social workers, and the bereaved parents. Parental interviews were conducted by YS at the child's home. A parental interview took place only if there was prior agreement by the child's general practitioner and by the parents. It included taking a detailed history of the child's life and of events leading up to the death. All informants were asked whether they felt there were any avoidable factors in the chain of events leading to the death.A committeeconsisting oftwo general practitioners, two consultant paediatricians, an area specialist in community medicine (child health), an area nurse (child health), a professor of clinical epidemiology,