CHDbase: A Comprehensive Knowledgebase for Congenital Heart Disease-related Genes and Clinical Manifestations.

Congenital heart disease (CHD) is one of themost common causes of major birth defects, with a prevalence of 1%. Although an increasing number of studies have reported the etiology of CHD, the findings scattered throughout the literature are difficult to retrieve and utilize in research and clinical practice. We therefore developed CHDbase, an evidence-based knowledgebase of CHD-related genes and clinical manifestations manually curated from 1114 publications, linking 1124susceptibility genes and 3591 variations to more than 300 CHD types and related syndromes. Metadata such as the information of each publication and the selected population and samples, the strategy of studies, and the major findings of studies were integrated with each item of the research record. We also integrated functional annotations through parsing ∼ 50 databases/tools to facilitate the interpretation of these genes and variations in disease pathogenicity. We further prioritized the significance of these CHD-related genes with a gene interaction network approach and extracted a core CHD sub-network with 163 genes. The clear genetic landscape of CHD enables the phenotype classification based on the shared genetic origin. Overall, CHDbase provides a comprehensive and freely available resource to study CHD susceptibilities, supporting a wide range of users in the scientific and medical communities. CHDbase is accessible at http://chddb.fwgenetics.org.

Simplifying Weighted Heterogeneous Networks by Extracting h-Structure via s-Degree.

In this study, we developed a method to extract the core structure of weighted heterogeneous networks by transforming the heterogeneous networks into homogeneous networks. Using the standardized z-score, we define the s-degree by summing all the z-scores of adjacent edges into base-nodes for a weighted heterogeneous network. Then, we rank all the s-degrees in decreasing order to obtain the core structure via the h-index of a base-homogeneous-network. After reducing all adjacent edges between the attribute nodes and base-nodes to the core structure, we obtain the heterogeneous core structure of the weighted network, which is called the h-structure. We find that the h-structure in a heterogeneous network contains less than 1% nodes and edges, which results in the construction of a highly effective simplification of a weighted heterogeneous network. Two practical cases, the citation network and the co-purchase network, were examined in this study.

Outcome of Patients with Complete Unilateral Cleft Lip and Palate: 20-Year Follow-Up of a Treatment Protocol.

BACKGROUND: The treatment plan for cleft lip and palate varies among centers and requires long-term evaluation of its final outcome. METHODS: A consecutive series of patients born from 1994 to 1996 were reviewed. Inclusion criteria were complete unilateral cleft lip and palate, undergoing all treatment procedures performed by the team, and continuous follow-ups until 20 years of age. Exclusion criteria were incomplete data, having microform cleft lip on the contralateral side, presence of the Simonart band, and other abnormalities. RESULTS: A total of 72 patients were included. Average age at final evaluation was 21.3 years; 83.3 percent of patients underwent one-stage rotation-advancement lip repair and 16.7 percent underwent two-stage repair with an initial adhesion cheiloplasty. All patients underwent palate repair using the two-flap method at an average age of 12.3 months. Velopharyngeal insufficiency occurred and required surgical interventions in 19.4 percent during the preschool age and in 16.7 percent at the time of alveolar bone grafting; 56.9 percent of patients underwent secondary lip/nose revision during the growing age. Regular orthodontic treatment was administered to 34.7 percent of patients between 12 and 16 years of age. Orthodontic treatment and orthognathic surgery were applied in 37.5 percent of the patients after maturity. The average number of surgical procedures to complete the treatment was 4.8 per patient. CONCLUSIONS: This treatment protocol provided generally acceptable final outcome after the 20-year follow-up. Some results were less ideal and have resulted in modifications of the planning and methods in the protocol. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Vomer flap for hard palate repair is related to favorable maxillary growth in unilateral cleft lip and palate.

OBJECTIVE: Vomer flap repair is assumed to improve maxillary growth because of reduced scarring in growth-sensitive areas of the palate. Our aim was to evaluate whether facial growth in patients with unilateral cleft lip and palate was significantly affected by the technique of hard palate repair (vomer flap versus two-flap). MATERIALS AND METHODS: For this retrospective longitudinal study, we analyzed 334 cephalometric radiographs from 95 patients with nonsyndromic complete unilateral cleft lip and palate who underwent hard palate repair by two different techniques (vomer flap versus two-flap). Clinical notes were reviewed to record treatment histories. Cephalometry was used to determine facial morphology and growth rate. The associations among facial morphology at age 20, facial growth rate, and technique of hard palate repair were assessed using generalized estimating equation analysis. RESULTS: The hard palate repair technique significantly influenced protrusion of the maxilla (SNA: ß = -3.5°, 95 % CI = -5.2-1.7; p = 0.001) and the anteroposterior jaw relation (ANB: ß = -4.2°, 95 % CI = -6.4-1.9; p = 0.001; Wits: ß = -5.7 mm, 95 % CI = -9.6-1.2; p = 0.01) at age 20, and their growth rates (SNA p = 0.001, ANB p < 0.01, and Wits p = 0.02). CONCLUSIONS: The results suggest that in patients with unilateral cleft lip and palate, vomer flap repair has a smaller adverse effect than two-flap on growth of the maxilla. This effect on maxillary growth is on the anteroposterior development of the alveolar maxilla and is progressive with age. We now perform hard palate closure with vomer flap followed by soft palate closure using Furlow palatoplasty. CLINICAL RELEVANCE: These findings may improve treatment outcome by modifying the treatment protocol for patients with unilateral cleft lip and palate.

Use of hemisphincter pharyngoplasty in the management of velopharyngeal insufficiency after pharyngeal flap: an outcome study.

Superiorly based pharyngeal flaps (PFs) are commonly used for the treatment of velopharyngeal insufficiency (VPI) in patients with cleft palate. However, failure may occur with recurrence of hypernasality and surgical revision may be necessary. Hemisphincter pharyngoplasty using either unilateral or bilateral posterior tonsillar pillars with the underlying palatopharyngeus muscle can be used to narrow the incompetent lateral portals. We retrospectively reviewed 22 patients diagnosed with VPI after PF surgery, who underwent hemisphincter pharyngoplasty from 1995 to 2007. Seventeen patients with complete speech assessment records were evaluated for the surgical outcome. Overall velopharyngeal function improvement was 88.2%. Symptoms of airway obstruction developed in 41% of the patients perioperatively. All of them improved gradually except 1 patient who needed continuous positive airway pressure mask treatment for obstructive sleep apnea. It is concluded that hemisphincter pharyngoplasty for narrowing of the incompetent portals is an effective treatment of VPI after PF.

Two-stage palate repair with delayed hard palate closure is related to favorable maxillary growth in unilateral cleft lip and palate.

BACKGROUND: Two-stage palate repair with delayed hard palate closure is generally advocated because it allows the best possible postoperative maxillary growth. Nevertheless, in the literature, it has been questioned whether maxillary growth is better following use of this protocol. The authors therefore aimed to investigate whether stage of palate repair, one-stage versus two-stage, had a significant effect on facial growth in patients with unilateral cleft lip and palate. METHODS: Seventy-two patients with nonsyndromic complete unilateral cleft lip and palate operated on by two different protocols for palate repair, one-stage versus two-stage with delayed hard palate closure, and their 223 cephalometric radiographs were available in the retrospective longitudinal study. Clinical notes were reviewed to record treatment histories. Cephalometry was used to determine facial morphology and growth rate. Generalized estimating equations analysis was performed to assess the relationship between (1) facial morphology at age 20 and (2) facial growth rate, and the stage of palate repair. RESULTS: Stage of palate repair had a significant effect on the length and protrusion of the maxilla and the anteroposterior jaw relation at age 20, but not on their growth rates. CONCLUSIONS: The data suggest that in patients with unilateral cleft lip and palate, two-stage palate repair has a smaller adverse effect than one-stage palate repair on the growth of the maxilla. This stage effect is on the anteroposterior development of the maxilla and is attributable to the development being undisturbed before closure of the hard palate (i.e., hard palate repair timing specific).

Management of velopharyngeal insufficiency in the presence of enlarged tonsils: comparing a one-stage versus two-stage treatment result.

Alterations in velopharyngeal function after removal of enlarged tonsils were noted. However, the changes varied from previous reports. The purposes of this study were to examine the effect of tonsillectomy on velopharyngeal function and to look for proper management of velopharyngeal insufficiency in the presence of enlarged tonsils. Thirty patients who received tonsillectomy at one craniofacial centre were reviewed. The influence of tonsillectomy on velopharyngeal function was examined and correlations to nasopharyngoscopic or videofluoroscopic findings were made. The outcomes between simultaneous and staged tonsillectomy and velopharyngeal surgery were compared. Tonsillectomy was found to either improve or impair velopharyngeal function in a small proportion of patients; however, it did not alter the surgical management of velopharyngeal insufficiency. Nasopharyngoscopic or videofluoroscopic findings did not predict the influence of tonsillectomy on velopharyngeal function. Finally, simultaneous tonsillectomy and velopharyngeal surgery had an efficacy and complication rate comparable to that of the staged approach.

Cleft oronasal fistula: a review of treatment results and a surgical management algorithm proposal.

BACKGROUND: Oronasal fistulas (ONF) following cleft palate repair are commonly encountered and remain a challenging problem. With reported recurrence rates between 33% and 37%, this urges us to critically evaluate the current treatment and propose a surgical management protocol. METHODS: A retrospective study of patients treated for ONF by a single surgeon between 1995 and 2005 was performed. Data regarding cleft type, age at palate repair, complications, location and size of fistula, tissue condition, surgical technique employed, and success rate were gathered. RESULTS: There were 64 patients (33 male and 31 female), and 44% of them had bilateral cleft lip and palate. Hypernasality and regurgitation were the major presenting symptoms of these patients with ONF. Fistulas mostly occurred in the hard palate area (53.1%). Severe scarring surrounding the ONF was reported in 31.2% of patients. Local flap and two-flap palatoplasty were the most common techniques (62.5%) used for closure of the ONF. Twenty-five percent of patients needed more than one repair to close the fistula. However, the overall success rate of closure was high (90.5%). Velopharyngeal (VP) function was significantly improved: only 26.8% of patients had adequate VP function before ONF closure and 64.3% patients had adequate VP function after ONF closure. However, the VP function of twenty patients remained inadequate or marginal. CONCLUSIONS: A high success rate was achieved for closure of cleft ONF, although a certain percentage of patients required re-operation. Multiple fistulas and severely scarred palates made closure difficult. Successful closure of a fistula improved VP function but VP surgery was still indicated in certain patients. Based on the findings, an algorithm for management of cleft ONF was proposed.

United States coronary mortality trends and community services associated with occupational structure, among blacks and whites, 1984-1998.

This paper examines the association between US county occupational structure, services availability, prevalence of risk factors, and coronary mortality rates by sex and race, for 1984-1998. The 3137 US counties were classified into five occupational structure categories; counties with the lowest percentages of the labor force in managerial, professional, and technical occupations were classified in category I (5-16%), counties with the highest percentages were in category V (32-59%). Directly age-adjusted coronary heart disease (CHD) mortality rates, for aged 35-64 years, (from vital statistics and Census data), per-capita services (County Business Patterns), and the prevalence of CHD risk factors (Behavioral Risk Factor Surveillance Surveys data) were calculated for each occupational structure category. CHD mortality rates and the prevalence of risk factors were inversely monotonically associated with occupational structure categories for white men and women but not among black men and women. Numbers of producer services for banking, business credit, overall business services and personnel/employment services were 2-12 times greater in category V versus I counties. Consumer services such as fruit/vegetable markets, fitness facilities, doctor offices and social services were 1.6-3 times greater in category V versus I counties. Residential racial segregation scores remained high in most areas despite declines during 1980-1990; occupational segregation by race and gender were shown indicating continued institutional racism. An ecological model for conceptualizing communities and health and the overall influence of state and national occupational structure is discussed; intervention strategies such as decreased wage disparities and 'living wage' standards and development is discussed.