Psychosocial Functioning Among Children With and Without Differences of Sex Development.

OBJECTIVE: To assess health-related quality of life (HRQoL), psychosocial adjustment, and family functioning of children with differences of sex development (DSD) or cleft lip and/or palate (CL/P). METHODS: In this cross-sectional study, parents of children with DSD (n = 67), CL/P (n = 121), and a comparison group of unaffected youth (n = 126) completed standardized measures assessing family functioning and their children's HRQoL and psychosocial adjustment. Medical charts were abstracted for youth with either congenital condition. RESULTS: Children with DSD were rated as having significantly lower HRQoL and greater internalizing problems compared to youth with CL/P and unaffected youth. Children in the DSD group were also significantly more likely to fall into the clinical risk categories for total and internalizing problems relative to the CL/P and unaffected groups. Caregivers of children with DSD were significantly more likely to endorse items about child suicidality compared with caregivers in the CL/P and unaffected groups. No significant differences were found between groups for externalizing problems or the expressiveness domain of family functioning; parents of children with DSD reported significantly less family conflict relative to the other groups and greater cohesion relative to the unaffected group. Conclusions Youth with DSD appear to be at greater risk for psychosocial problems relative to children with CL/P and unaffected peers. Results underscore the need for integrated interdisciplinary care and ongoing psychosocial risk monitoring in youth with DSD.

Perceptions About Lactation Consultant Support, Breastfeeding Experiences and Postpartum Psychosocial Outcomes.

INTRODUCTION: Many women seek lactation consultant support in the postpartum period. Lactation consultant support in community or clinical settings is often assumed to extend breastfeeding duration, improve breastfeeding experiences, and be well-received. Few studies have assessed women's perceptions of the support they received, nor have perceptions been examined in relationship to breastfeeding outcomes and maternal well-being. Our objective was to characterize the lactation consultant support women received and examine how women's perceptions about the support related to their breastfeeding outcomes, anxiety and depressive symptoms, and parenting stress. METHODS: This observational, cross-sectional study examined receipt of postpartum lactation consultant support among 210 US women. Perceptions of lactation consultant support were examined in relation to breastfeeding outcomes, anxiety and depressive symptoms, and parenting stress to explore outcomes of negative versus positive lactation consultant support experiences, using linear and proportional hazards regression. RESULTS: While overall perceptions of lactation consultant support were positive for most recipients (71%, n = 98), 29% (n = 40) reported negative perceptions of lactation consultant support. Negative perceptions were associated with lower breastfeeding self-efficacy (ß = - 11.7, 95% CI - 17.3, - 6.0), a less successful breastfeeding experience (ß = - 19.5, CI - 27.8, - 11.3), greater general anxiety (ß = 6.5, CI 2.1, 10.9), and shorter total duration of milk production (HR = 0.39, 95% CI 0.18, 0.84). Perceptions were not associated with depressive symptoms or parenting stress. DISCUSSION: Findings highlight the importance of ensuring that postpartum breastfeeding support provided by lactation consultants is perceived as positive by women.

Adherence to Orthodontic Treatment in Youth With Cleft Lip and/or Palate.

OBJECTIVE: To identify rates of nonadherence to orthodontic treatment among youth with cleft lip and/or palate (CL/P) and to compare demographic and clinical characteristics of patients categorized as adherent or nonadherent. DESIGN: Retrospective chart review. SETTING: Orthodontic treatment program affiliated with a US pediatric hospital-based craniofacial team. PARTICIPANTS: Medical charts of 54 patients with CL/P beginning phase I or phase II orthodontics between 2011 and 2014 (54% male; mean age: 11.7 ± 3.2 years) were reviewed. MAIN OUTCOME MEASURE(S): Data abstracted included demographic and clinical characteristics. Patients were classified as nonadherent based upon treatment termination due to nonadherence, treatment courses extending beyond 3 years, and information about missed appointments, poor oral hygiene, and broken appliances. RESULTS: In all, 24% had treatment terminated due to nonadherence and were significantly more likely to have behavioral health diagnoses (P = .01) or visits (P = .02) and social work consults (P = .01) than patients without termination. Thirty-seven percent had treatment courses beyond 3 years; youth with longer courses were significantly more likely to have cleft lip and palate versus cleft palate only or cleft lip (P = .03). Patients who missed more than 4 appointments were less likely to have behavioral health diagnoses (P < .01) compared to those with fewer missed appointments. Poor hygiene and broken appliance notations were common. Youth with poor hygiene notations were significantly older (P < .01) at treatment initiation than those without notations. CONCLUSIONS: Nonadherence was associated with diagnosis, age, and history of behavioral health or social work involvement. An understanding of adherence and relationships with clinical and demographic factors can inform clinical care and support intervention development to improve outcomes.

Adherence to Orthodontic Treatment in Youth With Craniofacial Conditions: A Survey of US Orthodontists.

OBJECTIVE: (1) To explore orthodontists' perceptions of nonadherence and related factors in their patients with craniofacial conditions; (2) to examine differences in adherence perceptions by provider characteristics; (3) to evaluate current adherence interventions. DESIGN: Cross-sectional. SETTING: United States-based orthodontists affiliated with a nonprofit association for providers treating oral cleft and craniofacial conditions received survey invitations via list-serv, e-mail, and social media. PARTICIPANTS: Thirty-eight orthodontists participated (mean age = 50.5 ± 10.7 years; 76% Caucasian; 55% male; 54% private practice). MAIN OUTCOME MEASURE: An 80-item survey assessed demographic characteristics; frequencies of various adherence problems and adherence-related prolonged or terminated treatment; importance of adherence to treatment outcomes; factors that may impact adherence; interest in improving adherence; and use of adherence-enhancing interventions. RESULTS: Adherence problems were common, yet 80.6% of participants rated adherence as "very important" to cleft treatment outcomes. Child behavior and motivation, caregiver reinforcement of behavior, and provider communication with the family were identified as factors that greatly impact adherence. Orthodontists in university-affiliated programs were more likely to rate individual, family, health-care system, and community factors as impacting adherence compared to private practice orthodontists; 80.6% used adherence interventions; these strategies were all rated as "sometimes successful." CONCLUSIONS: Nonadherence to cleft lip/palate-related orthodontic care is common and potentially detrimental to care. Current interventions are not uniformly successful and could be better tailored. Understanding provider, patient, and family factors that affect adherence can inform individualized treatment planning to improve adherence and ultimately, treatment outcomes.

Assessment of Psychosocial Risk in Families of Children With Craniofacial Conditions Using the Psychosocial Assessment Tool-Craniofacial Version.

OBJECTIVES: Using the Psychosocial Assessment Tool-Craniofacial Version (PAT-CV), this study measured variation in psychosocial risk in families of children with craniofacial conditions by demographic and clinical characteristics, frequency of condition-related problems, concordance between caregivers' report of risk, and association between risk level and psychosocial service utilization. DESIGN: Caregivers (n = 242) of 217 children with craniofacial conditions completed the PAT-CV, a psychosocial risk screener. Medical records were also abstracted. RESULTS: The PAT-CV scores varied significantly by insurance type and syndromic versus nonsyndromic diagnosis type. Language problems were most commonly reported on the Craniofacial Problems subscale, though 13% to 56% of parents endorsed specific problems. Mothers and fathers reported similar risk levels. Families with past social work or behavioral health consults had higher PAT-CV scores than those without consultations. CONCLUSION: The PAT-CV efficiently screens for psychosocial risk and craniofacial-specific problems. This tool may help clinicians identify families in need of intervention.

Identifying Psychosocial Risk Factors Among Families of Children With Craniofacial Conditions: Validation of the Psychosocial Assessment Tool-Craniofacial Version.

OBJECTIVE: To evaluate the psychometric properties of the Psychosocial Assessment Tool-Craniofacial Version (PAT-CV), a screening instrument for psychosocial risk in families of children with craniofacial conditions, and to examine risk classification of patients in a craniofacial population. DESIGN: Prospective, cross-sectional, single-center study. SETTING: Interdisciplinary cleft lip and palate/craniofacial center at a US children's hospital. PARTICIPANTS: Parents/caregivers (n = 242) of 217 children ages 1 month to 17 years being treated for a congenital syndromic or nonsyndromic craniofacial condition completed the PAT-CV and validating measures from July 2015 to July 2016. The PAT-CV was completed by 121 caregivers a second time to assess test-retest reliability. MAIN OUTCOME MEASURES: PAT-CV, Child Behavior Checklist, Adult Self-Report, Pediatric Quality of Life Inventory, Craniofacial Experiences Questionnaire, and Family Environment Scale. RESULTS: Construct validity of the PAT-CV was supported by significant correlations ( P < .001) between PAT-CV total and subscale scores and the validated measures. PAT-CV total scores categorized 59.9% of families within the universal risk group, 32.3% within the targeted risk group, and 7.8% within the clinical range. Good criterion validity was indicated by significantly higher scores ( P < .0001) obtained on the validated measures for those in the targeted and clinical risk groups. Internal consistency (Cronbach's α = 0.86) and test-retest reliability for the PAT-CV total score ( r = 0.77, P < .0001) were acceptable. CONCLUSIONS: The PAT-CV appears to be a reliable and valid screening instrument for psychosocial risk. Accurate identification of risk and implementation of appropriate interventions may contribute to improvements in medical and psychosocial outcomes.

Body Image Dissatisfaction, Breastfeeding Experiences, and Self-Efficacy in Postpartum Women with and Without Eating Disorder Symptoms.

BACKGROUND: Women during the postpartum period undergo significant changes which affect body image, eating behaviors, and, potentially, breastfeeding. There is limited research about relationships among these variables, particularly related to breastfeeding experiences and self-efficacy. RESEARCH AIMS: To determine: (1) the associations between eating disorder symptoms and body image, breastfeeding self-efficacy, and breastfeeding experiences; and (2) the differences in body image, breastfeeding self-efficacy, breastfeeding experiences, and breastfeeding status of postpartum women with and without clinically significant eating disorder symptoms. METHODS: A secondary data analysis using a 2-group correlational, cross-sectional online survey design was used. Participants with infants 2-6 months old who had breastfed their infant at least once (N = 204) were recruited nationally to complete a cross-sectional survey assessing breastfeeding and postpartum physical and mental health using validated measures. Linear and logistic regression evaluated differences between participants with and without eating disorder symptoms regarding their body image, breastfeeding experience and self-efficacy, and breastfeeding status (continued vs. discontinued) at 2 months postpartum. RESULTS: Clinical eating disorder symptoms were reported by 9.8% (n = 20). Participants with clinical eating disorder symptoms reported lower appearance evaluations (B = -0.53, 95% CI [-0.93, -0.14]) and body image satisfaction (B = -0.55, 95% CI [-0.87, -0.23]); reduced odds of breastfeeding at 2 months postpartum (AOR = 0.15, 95% CI [0.04, 0.56]); and lower breastfeeding self-efficacy (B = -7.70, 95% CI [-14.82, -0.58] relative to participants without clinical symptoms. No differences between groups were observed for breastfeeding experiences. CONCLUSIONS: Participants with clinically significant eating disorder symptoms are at risk for early breastfeeding discontinuation and lower breastfeeding self-efficacy. Our findings have implications for future research and clinical care practices, including screening for body image concerns and eating disorder symptoms and supporting breastfeeding self-efficacy.

Cloning and functional expression of invertebrate connexins from Halocynthia pyriformis.

Unlike many other ion channels, unrelated gene families encode gap junctions in different animal phyla. Connexin and pannexin genes are found in deuterostomes, while protostomal species use innexin genes. Connexins are often described as vertebrate genes, despite the existence of invertebrate deuterostomes. We have cloned connexin sequences from an invertebrate chordate, Halocynthia pyriformis. Invertebrate connexins shared 25-40% sequence identity with human connexins, had extracellular domains containing six invariant cysteine residues, coding regions that were interrupted by introns, and formed functional channels in vitro. These data show that gap junction channels based on connexins are present in animals that predate vertebrate evolution.

Cilnidipine is a novel slow-acting blocker of vascular L-type calcium channels that does not target protein kinase C.

Cilnidipine is a novel dihydropyridine (DHP) antagonist. However, its pharmacological effects on vascular DHP-sensitive L-type channels and protein kinase C (PKC)-mediated arterial contraction is incompletely understood. To address this issue, we studied the effects of cilnidipine on multi-subunit, C-class L-type Ca2+ channels in rat aortic A7r5 cells, as well as on Ca2+ channel (L-type) alpha1C-b and (T-type) alpha1G subunits in the Xenopus oocyte expression system. Cilnidipine dose- and time-dependently inhibited Ba2+ currents in A7r5 cells, with half-maximal inhibitions (IC50) at 10 nmol/l after 10 min. Unlike classical pharmacological Ca2+ channel blockers, cilnidipine's block of Ca2+ currents did not reach steady-state levels within 10 min, indicating steady-state half-maximal inhibition of native, multi-subunit L-type channels at < 10 nmol/l. In contrast, smooth muscle alpha1Cb currents were blocked by cilnidipine at much higher doses (steady-state IC50, 20 micromol/l) whereas alpha1G currents were not inhibited by cilnidipine (30 micromol/l). Cilnidipine dose-dependently inhibited depolarization- and Ca2+-induced contractions of rat aortic rings, with an IC50 of 10 nmol/l at 10 min. However, the onset of the effects was very slow, with approximately 71% inhibition by 3 nmol/l cilnidipine after 90 min exposure to cilnidipine. In contrast, cilnidipine did not inhibit phorbol 12-myristate-13-acetate (100 nmol/l)-mediated contractions. We conclude that cilnidipine represents an extremely slow-acting DHP that targets multi-subunit L-type channels, but not PKC in arterial smooth muscle. Because cilnidipine is less potent in cells expressing the pore-forming alpha1C-b subunit, the data further suggest that this unique slow-acting mechanism of cilnidipine is mediated by a complex interaction of cilnidipine with alpha1C-b and accessory channel subunits.

"Zebrafishing" for novel genes relevant to the glomerular filtration barrier.

Data for genes relevant to glomerular filtration barrier function or proteinuria is continually increasing in an era of microarrays, genome-wide association studies, and quantitative trait locus analysis. Researchers are limited by published literature searches to select the most relevant genes to investigate. High-throughput cell cultures and other in vitro systems ultimately need to demonstrate proof in an in vivo model. Generating mammalian models for the genes of interest is costly and time intensive, and yields only a small number of test subjects. These models also have many pitfalls such as possible embryonic mortality and failure to generate phenotypes or generate nonkidney specific phenotypes. Here we describe an in vivo zebrafish model as a simple vertebrate screening system to identify genes relevant to glomerular filtration barrier function. Using our technology, we are able to screen entirely novel genes in 4-6 weeks in hundreds of live test subjects at a fraction of the cost of a mammalian model. Our system produces consistent and reliable evidence for gene relevance in glomerular kidney disease; the results then provide merit for further analysis in mammalian models.

Nephrogenesis is induced by partial nephrectomy in the elasmobranch Leucoraja erinacea.

The mammalian kidney responds to partial nephrectomy with glomerular and tubular hypertrophy, but without renal regeneration. In contrast, renal regeneration in lower vertebrates is known to occur. Understanding the underlying mechanisms of renal regeneration is highly important; however, a serviceable animal model has not been developed. A neonephrogenic zone has been identified in the European lesser spotted dogfish, Scyliorhinus caniculus (Hentschel H. Am J Anat 190: 309-333, 1991), as well as in the spiny dogfish Squalus acanthias and the little skate, Leucoraja erinacea. The zone features the production of new nephrons complete with a countercurrent system. To analyze this nephrogenic region of elasmobranch fish further, a renal reduction model was established. The neonephrogenic zone in the adult kidney of the little skate resembles the embryonic metanephric kidney and contains stem cell-like mesenchymal cells, tips of the branching collecting duct system, and outgrowth of the arterial system. Four stages of nephron development were analyzed by serial sections and defined: stage I, aggregated mesenchymal cells; stage II, S-shaped body-like structure with high-prismatic epithelial cells; stage III, segmental nephron segregation; stage IV, functioning nephron. The stages were analyzed after partial nephrectomy. In addition, cell proliferation was assessed by incorporation of bromo-deoxyuridine (BrdU). New nephrons developed in animals undergoing partial nephrectomy. Growth was greatly stimulated in the nephrogenic zone, both in the remnant tissue and in the contralateral kidney within 10 wk. Mesenchymal cell aggregates increased significantly per renal cross-section compared with controls (stage I, 0.64 +/- 0.28 versus 0.27 +/- 0.25; P < 0.005; n = 10 animals per group). The same was the case for S-shaped body-like cysts (stage II, 0.24 +/- 0.19 versus 0.08 +/- 0.09; P < 0.02). Cellular proliferation in the neonephrogenic zone of the contralateral kidney was also greatly enhanced (14.42 +/- 3.26 versus 2.64 +/- 1.08 BrdU-positive cells per cross-section, P < 0.001). It is concluded that the skate possesses a nephrogenic zone containing stem cell-like mesenchymal cells during its entire life. Partial nephrectomy induces renal growth by accelerating nephrogenesis. This unique model may facilitate understanding renal regeneration.