Clear as Mud: Readability Scores in Cloacal Exstrophy Literature and Its Treatment.

Purpose: This study examines the readability of online medical information regarding cloacal exstrophy (CE). We hypothesize that inappropriate levels of comprehension are required in these resources, leading to poor understanding and confusion amongst caregivers. Methods: The Google and Bing search engines were used to search the terms "cloacal exstrophy" and "cloacal exstrophy treatment". The first 100 results for each were collected. Each webpage was analyzed for readability using four independent validated scoring systems: the Gunning-Fog index (GFI), SMOG grade (Simple Measure of Gobbledygook), Dale-Chall index (DCI), and the Flesch-Kincaid grade (FKG). Results: Forty-seven unique webpages fit the inclusion criteria. Mean readability scores across all websites were GFI, 14.6; SMOG score, 10.8; DCI, 9.3; and FKG, 11.8, correlating to adjusted grade levels of college sophomore, 11th grade, college, and 11th grade, respectively. There were significant differences across all readability formulas. Non-profit websites were significantly less readable than institutional and commercial webpages (GFI p = 0.012, SMOG p = 0.018, DCI p = 0.021, FKG p = 0.0093). Conclusion: Caregiver-directed health information regarding CE and its treatment available online is written at the 11th grade reading level or above. Online resources pertaining to CE must be simplified to be effective.

Phenotype severity in the bladder exstrophy-epispadias complex: analysis of genetic and nongenetic contributing factors in 441 families from North America and Europe.

OBJECTIVE: To identify genetic and nongenetic risk factors that contribute to the severity of the bladder exstrophy-epispadias complex (BEEC). STUDY DESIGN: Patients with BEEC from North America (n = 167) and Europe (n = 274) were included. The following data were collected: associated anomalies, parental age at conception, mode of conception, periconceptional folic acid supplementation, maternal risk factors during pregnancy, and environmental risk factors. The patients were divided into 3 subgroups according to phenotype severity: (i) mild, epispadias (n = 43); (ii) intermediate, classic bladder exstrophy (n = 366); and (iii) severe, cloacal exstrophy (n = 31). These subgroups then were compared with identify factors that contribute to phenotype severity. RESULTS: Males were overrepresented in all subgroups. A relatively high prevalence of cleft lip, with or without cleft palate, was observed. Maternal smoking and medical radiation during the first trimester were associated with the severe cloacal exstrophy phenotype. Compliance with periconceptional folic acid supplementation was associated with the mildest phenotype (epispadias). CONCLUSIONS: Periconceptional folic acid supplementation appears to prevent the development of the severe phenotype of BEEC.

Molecular effects of genistein on male urethral development.

PURPOSE: The increasing incidence of hypospadias is partly attributed to increased gestational exposure to endocrine disruptors. We investigated the effects of genistein, the primary phytoestrogen in soy, on the molecular program of male urethral development. MATERIALS AND METHODS: Female mice were fed diets supplemented with genistein (500 mg/kg diet) or control diets before breeding and throughout gestation. Urethras from embryonic day 17.5 male fetuses were harvested, and RNA was prepared, amplified, labeled and hybridized on whole genome microarrays. Data were analyzed using packages from the R/Bioconductor project. Immunohistochemical analysis and immunoblotting were used to confirm the activity of MAPK and the presence of Ntrk1 and Ntrk2 during urethral development. RESULTS: Gestational exposure to genistein altered the urethral expression of 277 genes (p <0.008). Among the most affected were hormonally regulated genes, including IGFBP-1, Kap and Rhox5. Differentially expressed genes were grouped into functional pathways of cell proliferation, adhesion, apoptosis and tube morphogenesis (p <0.0001), and were enriched for members of the MAPK (p <0.00001) and TGF-ß (p <0.01) signaling cascades. Differentially expressed genes preferentially contained ELK1, Myc/Max, FOXO, HOX and ER control elements. The MAPK pathway was active, and its upstream genistein affected tyrosine kinase receptors Ntrk1 and Ntrk2 were present in the developing male urethra. CONCLUSIONS: Gestational exposure to genistein contributes to hypospadias by altering pathways of tissue morphogenesis, cell proliferation and cell survival. In particular, genes in the MAPK and TGF-ß signaling pathways and those controlled by FOXO, HOX and ER transcription factors are disrupted.

Perinatal exposure to genistein alters reproductive development and aggressive behavior in male mice.

Exposure to endocrine disrupting chemicals adversely affects reproductive development and behavior in males. The goal of this study was to determine if exposure to genistein, an isoflavone found in soy, during early periods of sex differentiation alters reproductive development and behavior in male mice. Female C57BL/6 mice were fed a phytoestrogen-free diet supplemented with 0, 5 or 300 mg/kg of genistein throughout gestation and lactation. Anogenital distance (AGD) and body mass of male offspring was measured weekly from postnatal days 2-21, timing of preputial separation was assessed at puberty, and in adulthood, reproductive organ masses, sperm and testosterone production, and reproductive and aggressive behaviors were assessed. Exposure to genistein resulted in smaller AGD are reduced body mass, with the low-dose diet exerting a greater effect. Timing of preputial separation, adult reproductive behavior, sperm concentrations and testosterone production were not influenced by genistein treatment at either dose. Aggressive behaviors were decreased, whereas defensive behaviors were increased, in males that received the low-dose genistein diet. Exposure to genistein during critical periods of sex differentiation results in concurrent and persistent demasculinization in male mice. Phenotypic and behavioral abnormalities induced by genistein showed a non-monotonic response, where treatment with a low dose exerted a greater effect than treatment with a high dose of genistein. Given the popularity of soy infant formulas, the influence isoflavone exposure on reproductive and behavioral health in boys and men should be considered.