Transcription Factor MYB26 Is Key to Spatial Specificity in Anther Secondary Thickening Formation.

Successful fertilization relies on the production and effective release of viable pollen. Failure of anther opening (dehiscence), results in male sterility, although the pollen may be fully functional. MYB26 regulates the formation of secondary thickening in the anther endothecium, which is critical for anther dehiscence and fertility. Here, we show that although the MYB26 transcript shows expression in multiple floral organs, the MYB26 protein is localized specifically to the anther endothecium nuclei and that it directly regulates two NAC domain genes, NST1 and NST2, which are critical for the induction of secondary thickening biosynthesis genes. However, there is a complex relationship of regulation between these genes and MYB26. Using DEX-inducible MYB26 lines and overexpression in the various mutant backgrounds, we have shown that MYB26 up-regulates both NST1 and NST2 expression. Surprisingly normal thickening and fertility rescue does not occur in the absence of MYB26, even with constitutively induced NST1 and NST2, suggesting an additional essential role for MYB26 in this regulation. Combined overexpression of NST1 and NST2 in myb26 facilitates limited ectopic thickening in the anther epidermis, but not in the endothecium, and thus fails to rescue dehiscence. Therefore, by a series of regulatory controls through MYB26, NST1, NST2, secondary thickening is formed specifically within the endothecium; this specificity is essential for anther opening.

Early-Onset Invasive Candidiasis in Extremely Low Birth Weight Infants: Perinatal Acquisition Predicts Poor Outcome.

BACKGROUND: Neonatal invasive candidiasis (IC) presenting in the first week of life is less common and less well described than later-onset IC. Risk factors, clinical features, and disease outcomes have not been studied in early-onset disease (EOD, ≤7 days) or compared to late-onset disease (LOD, >7 days). METHODS: All extremely low birth weight (ELBW, <1000 g) cases with IC and controls from a multicenter study of neonatal candidiasis enrolled from 2001 to 2003 were included in this study. Factors associated with occurrence and outcome of EOD in ELBW infants were determined. RESULTS: Forty-five ELBW infants and their 84 matched controls were included. Fourteen (31%) ELBW infants had EOD. Birth weight <750 g, gestation <25 weeks, chorioamnionitis, and vaginal delivery were all strongly associated with EOD. Infection with Candida albicans, disseminated disease, pneumonia, and cardiovascular disease were significantly more common in EOD than in LOD. The EOD case fatality rate (71%) was higher than in LOD (32%) or controls (15%) (P = .0001). The rate of neurodevelopmental impairment and mortality combined was similar in EOD (86%) and LOD (72%), but higher than in controls (32%; P = .007). CONCLUSIONS: ELBW infants with EOD have a very poor prognosis compared to those with LOD. The role of perinatal transmission in EOD is supported by its association with chorioamnionitis, vaginal delivery, and pneumonia. Dissemination and cardiovascular involvement are common, and affected infants often die. Empiric treatment should be considered for ELBW infants delivered vaginally who have pneumonia and whose mothers have chorioamnionitis or an intrauterine foreign body.

How to use nasal nitric oxide in a child with suspected primary ciliary dyskinesia.

Measuring nasal nitric oxide (nNO) is increasingly used as part of testing for primary ciliary dyskinesia (PCD). The diagnosis of PCD is often delayed until after bronchiectasis is established and auditory damage has occurred. It is important that all paediatricians are aware of clinical features that are suggestive of PCD that should prompt diagnostic testing. nNO levels are recognised to be low in people with PCD and results generated by static chemiluminescence analysers using velum closure technique in older children have good sensitivity and specificity. However, to conclusively rule PCD in or out, further tests of ciliary function are required and assessment of cilia ultrastructure, immunohistochemistry studies and genotyping may also be indicated. These tests are more complex, invasive and expensive than nNO. nNO is less well studied in younger children where tidal breathing measurements are required. Portable nitric oxide analysers are also increasingly used in practice. This paper discusses when to consider PCD as a possible diagnosis in a child along with the indications, physiological and technical background and clinical utility of nNO as a test for PCD in children.

Invasive candidiasis in low birth weight preterm infants: risk factors, clinical course and outcome in a prospective multicenter study of cases and their matched controls.

BACKGROUND: This multicenter prospective study of invasive candidiasis (IC) was carried out to determine the risk factors for, incidence of, clinical and laboratory features, treatment and outcome of IC in infants of birth weight <1250 g. METHODS: Neonates <1250 g with IC and their matched controls (2:1) were followed longitudinally and descriptive analysis was performed. Survivors underwent neurodevelopmental assessment at 18 to 24 months corrected age. Neurodevelopmental impairment (NDI) was defined as blindness, deafness, moderate to severe cerebral palsy, or a score <70 on the Bayley Scales of Infant Development 2nd edition. Multivariable analyses were performed to determine risk factors for IC and predictors of mortality and NDI. RESULTS: Cumulative incidence rates of IC were 4.2%, 2.2% and 1.5% for birth-weight categories <750 g, <1000 g, <1500 g, respectively. Forty nine infants with IC and 90 controls were enrolled. Necrotizing enterocolitis (NEC) was the only independent risk factor for IC (p=0.03). CNS candidiasis occurred in 50% of evaluated infants, while congenital candidiasis occurred in 31%. Infants with CNS candidiasis had a higher mortality rate (57%) and incidence of deafness (50%) than the overall cohort of infants with IC. NDI (56% vs. 33%; p=0.017) and death (45% vs. 7%; p=0.0001) were more likely in cases than in controls, respectively. IC survivors were more likely to be deaf (28% vs. 7%; p=0.01). IC independently predicted mortality (p=0.0004) and NDI (p=0.018). CONCLUSION: IC occurred in 1.5% of VLBW infants. Preceding NEC increased the risk of developing IC. CNS candidiasis is under-investigated and difficult to diagnose, but portends a very poor outcome. Mortality, deafness and NDI were independently significantly increased in infants with IC compared to matched controls.

Characteristics and outcome of infants with candiduria in neonatal intensive care - a Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study.

BACKGROUND: There is limited information in the literature on the presentation and prognosis of candidal urinary tract infection (UTI) in infants in the neonatal intensive care unit (NICU). METHODS: This was a prospective cohort study performed in 13 Canadian NICUs. Infants with candidal UTI without extra-renal candidal infection at presentation were enrolled. RESULTS: Thirty infants fit the study criteria. Median birth weight and gestational age were 2595 grams (range 575-4255) and 35 weeks (range 24-41) with 10 infants being < 30 weeks gestation. The most common primary underlying diagnosis was congenital heart disease (n = 10). The median age at initial diagnosis was 16 days (range 6-84 days). Renal ultrasonography findings were compatible with possible fungal disease in 15 of the 26 infants (58%) in whom it was performed. Treatment was variable, but fluconazole and either amphotericin B deoxycholate or lipid-based amphotericin B in combination or sequentially were used most frequently. Extra-renal candidiasis subsequently developed in 4 infants. In 2 of these 4 infants, dissemination happened during prolonged courses of anti-fungal therapy. Three of 9 deaths were considered to be related to candidal infection. No recurrences of candiduria or episodes of invasive candidiasis following treatment were documented. CONCLUSION: Candidal UTI in the NICU population occurs both in term infants with congenital abnormalities and in preterm infants, and is associated with renal parenchymal disease and extra-renal dissemination. A wide variation in clinical approach was documented in this multicenter study. The overall mortality rate in these infants was significant (30%). In one third of the deaths, Candida infection was deemed to be a contributing factor, suggesting the need for antifungal therapy with repeat evaluation for dissemination in infants who are slow to respond to therapy.

Microbiologic findings and risk factors for antimicrobial resistance at myringotomy for tympanostomy tube placement--a prospective study of 601 children in Toronto.

CONTEXT: There is limited information on the identity and antibiotic susceptibility of bacterial pathogens in children with chronic otitis media whose repeated antibiotic use may place them at increased risk of antibiotic-resistant bacteria. OBJECTIVE: To determine, at myringotomy for tympanostomy tube placement, (1) the prevalence of bacteria, (2) the extent and patterns of antibiotic resistance, and (3) the risk factors associated with the presence and resistant status of pathogens. DESIGN: Prospective, multi-site, cohort study. SETTING AND PATIENTS: Children undergoing myringotomy for tympanostomy tube placement between November 1, 1999 and March 31, 2000 in seven hospitals in Toronto, Ontario, were identified. If fluid was present, aspirates were submitted for bacteriologic testing. A follow-up telephone questionnaire was administered to patient caregivers in order to identify risk factors for the presence of (1) culturable pathogens and (2) resistant pathogens. MAIN OUTCOME MEASURES: The identification and prevalence of bacteria cultured from the middle ears of subjects, and the degree of nonsusceptibility to commonly prescribed antibiotics. RESULTS: Among 601 patients (mean age 3.9 years, 60.7% male), both a telephone interview (n=544) and an ear specimen (n=527) were obtained for 478. Pathogens were found in middle ear effusions of 37% of the children in the study; including at least one 'definite' pathogen in 189 children (31.4%), and a further 32 children (5.3%) with at least one 'possible' pathogen. Definite pathogens included Haemophilus influenzae in 17% of the children, followed by Moraxella catarrhalis (9%) and Streptococcus pneumoniae (6%); ampicillin nonsusceptibility was found in 40, 100 and 24%, respectively. Overall, 123 children (20.5%) were found to have definite pathogens with resistance to ampicillin/penicillin, trimethoprim-sulfamethoxazole, or clarithromycin/erythromycin. Patient characteristics included premature birth and/or long length of stay in the nursery (23%), first infection before the age of 6 months (26%), put to bed with a bottle (28%), household smoker (34%), in out-of-home child care (38%), history of eczema, bronchiolitis and/or asthma (39%), and use of pacifiers (40%). Household characteristics were smoking (34%), married/common law parents (85%), and 60% had completed college or university; in 26% both parents were born outside of Canada; 73% of children were Caucasian. Of the 75% who responded to the question regarding income, 42% had household income over $60,000 (CAN). Risk factors for the presence of a pathogen and for a resistant pathogen in multivariate analysis included younger age, lower maternal education, day care centre attendance, no previous adenoidectomy and bilateral, primarily winter infections as well as amoxicillin use in the previous 6 months. CONCLUSION: Modifiable risk factors for otitis media including household smoking and pacifier use are present in many children undergoing tympanostomy tube placement; child care centre attendees are over-represented. Multiple antibiotic courses were commonly prescribed prior to surgery. H. influenzae and M. catarrhalis are important pathogens and therapy in clinical failures should be directed against them. The 7-valent protein conjugate polysaccharide vaccine (Prevnar) would have covered 73% of the serotypes of S. pneumoniae isolated in this study.

The epidemiology of juvenile onset recurrent respiratory papillomatosis derived from a population level national database.

OBJECTIVES/HYPOTHESIS: To develop a national database of cases of juvenile onset recurrent respiratory papillomatosis (JoRRP) in Canada, to calculate trends in incidence and prevalence of JoRRP from January 1994 to December 2007 at the national and regional level, and to mathematically model the natural history of JoRRP. STUDY DESIGN: Retrospective, multicenter study. METHODS: Patient demographics, clinical presentation, human papillomavirus status, method and timing of treatment, and indicators of disease severity were captured with a standardized case report form. Operative records were retrospectively scored using the Derkay-Coltrera staging system for each operative intervention. Trends in incidence and prevalence of JoRRP from 1994 to 2007 were calculated at a national and regional level using national population census data. A multivariable mixed effects linear model was used to explore the effect of surgery-specific variables on the intersurgical interval. Nonlinear least-squares regression was used to model the natural history of JoRRP. RESULTS: Development of a national database of children with JoRRP identified 243 cases who underwent 3,021 surgical procedures. The national incidence of JoRRP from 1994 to 2007 was 0.24 per 100,000 children aged 14 years and younger. The prevalence was 1.11 per 100,000 children. The natural history of JoRRP followed a nonlinear time course with 64% of cases having a decreasing annual rate of surgery over time. CONCLUSIONS: A Canadian national database of children with JoRRP was successfully developed. Modeling of the natural history of JoRRP may have important clinical and research implications.

Treating Anorexia Nervosa and Bulimia Nervosa.

Research on the treatment of eating disorders is a relatively new field, dating back approximately 20 years (Peterson & Mitchell, 1999). The purpose of this article is to describe the most widely used treatments for anorexia nervosa (AN) and bulimia nervosa (BN) and review the existing literature on the effectiveness of the identified treatments. Specifically, this article examines the effectiveness of cognitive-behavioral therapy, family therapy, interpersonal therapy, and pharmacotherapy in the treatment of AN and BN. Each of the reviewed treatment modalities has some level of effectiveness, either alone or in conjunction with another treatment approach, in treating either AN or BN.