Evaluating LINE-1 methylation in cleft lip tissues and its association with early pregnancy exposures

Aim: To pilot investigation of methylation of long interspersed nucleotide element-1 in lip tissues from infants with nonsyndromic cleft lip, and its association with maternal periconceptional exposures. Methods: The lateral and medial sides of the cleft lips of 23 affected infants were analyzed for long interspersed nucleotide element-1 methylation by bisulfite conversion and pyrosequencing. Results: The medial side showed 1.8% higher methylation compared with the lateral side; p = 0.031, particularly in male infants (2.7% difference; p = 0.011) or when the mothers did not take folic acid during periconceptional period (2.4% difference; p = 0.011). These results were not statistically significant when Bonferroni adjustment was used. Conclusion: The observed differences in DNA methylation, although nonsignificant after correction for multiple comparisons, suggest that differential regulation of the two sides may impact lip fusion and warrant larger-scale replication

Methods to estimate access to care and the effect of interventions on the outcomes of congenital disorders

In the absence of intervention, early-onset congenital disorders lead to pregnancy loss, early death, or disability. Currently, lack of epidemiological data from many settings limits the understanding of the burden of these conditions, thus impeding health planning, policy-making, and commensurate resource allocation. The Modell Global Database of Congenital Disorders (MGDb) seeks to meet this need by combining general biological principles with observational and demographic data, to generate estimates of the burden of congenital disorders. A range of interventions along the life course can modify adverse outcomes associated with congenital disorders. Hence, access to and quality of services available for the prevention and care of congenital disorders affects both their birth prevalence and the outcomes for affected individuals. Information on this is therefore important to enable burden estimates for settings with limited observational data, but is lacking from many settings. This paper, the third in this special issue on methods used in the MGDb for estimating the global burden of congenital disorders, describes key interventions that impact on outcomes of congenital disorders and methods used to estimate their coverage where empirical data are not available

The orthodontic-oral surgery interface. Part one: A service evaluation and overview of the diagnosis and management of common anomalies

Introduction: Complex dental anomalies often require multidisciplinary management in secondary care. These anomalies may present to general dental practitioners in the first instance, therefore it is important that all clinicians are aware of such anomalies and their management. / Aims: This service evaluation aimed to profile the dental anomalies presenting to the multidisciplinary joint dento-alveolar clinic at a district general hospital and to outline the management of the common anomalies. / Method: This two-part series details a service evaluation and profiles the dental anomalies presenting to the joint dento-alveolar clinic at a district general hospital. In addition, the features and management of the common dental anomalies are outlined. / Results: Fifty-four percent of patients were female, with a mean age of 17 years. The most common anomalies were impacted canines (49%), followed by supernumerary teeth (16%) and impacted premolars (10%). Other anomalies accounted for only a small percentage of referrals. / Conclusion: A wide range of anomalies presented to the joint dento-alveolar clinic. It is important for all clinicians to be aware of such anomalies, their diagnosis and management. Part one and two of this article therefore provide an overview of the common anomalies and highlight their management

Estimating the birth prevalence and pregnancy outcomes of congenital malformations worldwide

Congenital anomaly registries have two main surveillance aims: firstly to define baseline epidemiology of important congenital anomalies to facilitate programme, policy and resource planning, and secondly to identify clusters of cases and any other epidemiological changes that could give early warning of environmental or infectious hazards. However, setting up a sustainable registry and surveillance system is resource-intensive requiring national infrastructure for recording all cases and diagnostic facilities to identify those malformations that that are not externally visible. Consequently, not all countries have yet established robust surveillance systems. For these countries, methods are needed to generate estimates of prevalence of these disorders which can act as a starting point for assessing disease burden and service implications. Here, we describe how registry data from high-income settings can be used for generating reference rates that can be used as provisional estimates for countries with little or no observational data on non-syndromic congenital malformations

A multidisciplinary treatment of congenitally missing maxillary lateral incisors: a 14-year follow-up case report

Absence of the maxillary lateral incisor creates an aesthetic problem which can be managed in various ways. The condition requires careful treatment planning and consideration of the options and outcomes following either space closure or prosthetic replacement. Recent developments in restorative dentistry have warranted a re-evaluation of the approach to this clinical situation. Factors relating both to the patient and the teeth, including the presentation of malocclusion and the effect on the occlusion must be considered. The objective of this study was to describe the etiology, prevalence and alternative treatment modalities for dental agenesis and to present a clinical case of agenesis of the maxillary lateral incisors treated by the closure of excessive spaces and canine re-anatomization. A clinical case is presented to illustrate the interdisciplinary approach between orthodontics and restorative dentistry for improved esthetic results. In this report, the treatment of a girl with a Class II malocclusion of molars and canines with missing maxillary lateral incisors and convex facial profile is shown. Treatment was successfully achieved and included the space closure of the areas corresponding to the missing upper lateral incisors, through movement of the canines and the posterior teeth to mesial by fixed appliances as well as the canines transformation in the maxillary lateral incisors. This is a 14-year follow-up case report involving orthodontics and restorative dentistry in which pretreatment, posttreatment, and long-term follow-up records for the patient are presented

An assessment of orofacial clefts in Tanzania

<p>Abstract</p> <p>Background</p> <p>Clefts of the lip (CL), the palate (CP), or both (CLP) are the most common orofacial congenital malformations found among live births, accounting for 65% of all head and neck anomalies. The frequency and pattern of orofacial clefts in different parts of the world and among different human groups varies widely. Generally, populations of Asian or Native American origin have the highest prevalence, while Caucasian populations show intermediate prevalence and African populations the lowest. To date, little is known regarding the epidemiology and pattern of orofacial clefts in Tanzania.</p> <p>Methods</p> <p>A retrospective descriptive study was conducted at Bugando Medical Centre to identify all children with orofacial clefts that attended or were treated during a period of five years. Cleft lip and/or palate records were obtained from patient files in the Hospital's Departments of Surgery, Paediatrics and medical records. Age at presentation, sex, region of origin, type and laterality of the cleft were recorded. In addition, presence of associated congenital anomalies or syndromes was recorded.</p> <p>Results</p> <p>A total of 240 orofacial cleft cases were seen during this period. Isolated cleft lip was the most common cleft type followed closely by cleft lip and palate (CLP). This is a departure from the pattern of clefting reported for Caucasian and Asian populations, where CLP or isolated cleft palate is the most common type. The distribution of clefts by side showed a statistically significant preponderance of the left side (43.7%) (χ²= 92.4, p < 0.001), followed by the right (28.8%) and bilateral sides (18.3%). Patients with isolated cleft palate presented at very early age (mean age 1.00 years, SE 0.56). Associated congenital anomalies were observed in 2.8% of all patients with orofacial clefts, and included neural tube defects, Talipes and persistent ductus arteriosus.</p> <p>Conclusions</p> <p>Unilateral orofacial clefts were significantly more common than bilateral clefts; with the left side being the most common affected side. Most of the other findings did not show marked differences with orofacial cleft distributions in other African populations.</p

The effect of systematic pediatric care on neonatal mortality and hospitalizations of infants born with oral clefts

<p>Abstract</p> <p>Background</p> <p>Cleft lip and/or palate (CL/P) increase mortality and morbidity risks for affected infants especially in less developed countries. This study aimed at assessing the effects of systematic pediatric care on neonatal mortality and hospitalizations of infants with cleft lip and/or palate (CL/P) in South America.</p> <p>Methods</p> <p>The intervention group included live-born infants with isolated or associated CL/P in 47 hospitals between 2003 and 2005. The control group included live-born infants with CL/P between 2001 and 2002 in the same hospitals. The intervention group received systematic pediatric care between the 7^thand 28^thday of life. The primary outcomes were mortality between the 7^thand 28^thday of life and hospitalization days in this period among survivors adjusted for relevant baseline covariates.</p> <p>Results</p> <p>There were no significant mortality differences between the intervention and control groups. However, surviving infants with associated CL/P in the intervention group had fewer hospitalization days by about six days compared to the associated control group.</p> <p>Conclusions</p> <p>Early systematic pediatric care may significantly reduce neonatal hospitalizations of infants with CL/P and additional birth defects in South America. Given the large healthcare and financial burden of CL/P on affected families and the relatively low cost of systematic pediatric care, improving access to such care may be a cost-effective public policy intervention.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00097149">NCT00097149</a></p

Description of the methodology used in an ongoing pediatric care interventional study of children born with cleft lip and palate in South America [NCT00097149]

BACKGROUND: The contribution of birth defects, including cleft lip and palate, to neonatal and infant mortality and morbidity is substantial. As other mortality and morbidity causes including infections, hygiene, prematurity, and nutrition are eradicated in less developed countries, the burden of birth defects will increase proportionally. METHODS/DESIGN: We are using cleft lip and palate as a sentinel birth defect to evaluate its burden on neonatal and infant health and to assess the effectiveness of systematic pediatric care during the first month and first two years of life in decreasing this burden. The neonatal intervention, consisting of weekly pediatric evaluation and referral to appropriate care, is delivered to about 696 infants born with cleft lip and/or palate in 47 hospitals in South America. Neonatal mortality in this group will be compared to that in a retrospective control group of about 464 infants born with cleft lip and/or palate in the same hospitals. The subgroup of infants with isolated clefts of both the lip and palate (about 264) is also randomized into two groups, intervened and non-intervened, and further followed up over 2 years. Intervened cases are evaluated by pediatricians every three months and referred for appropriate care. The intervened and non-intervened cases will be compared over study outcomes to evaluate the intervention effectiveness. Non-intervened cases are matched and compared to healthy controls to assess the burden of cleft lip and palate. Outcomes include child's neurological and physical development and family social and economic conditions. DISCUSSION: Large-scale clinical trials to improve infant health in developing countries are commonly suggested, making it important to share the methods used in ongoing studies with other investigators implementing similar research. We describe here the content of our ongoing pediatric care study in South America. We hope that this may help researchers targeting this area to plan their studies more effectively and encourage the development of similar research efforts to target other birth defects or infant outcomes such as prematurity and low birth weight

Social, Structural and Behavioral Determinants of Overall Health Status in a Cohort of Homeless and Unstably Housed HIV-Infected Men

Background: Previous studies indicate multiple influences on the overall health of HIV-infected persons; however, few assess and rank longitudinal changes in social and structural barriers that are disproportionately found in impoverished populations. We empirically ranked factors that longitudinally impact the overall health status of HIV-infected homeless and unstably housed men. Methods and Findings: Between 2002 and 2008, a cohort of 288 HIV+ homeless and unstably housed men was recruited and followed over time. The population was 60 % non-Caucasian and the median age was 41 years; 67 % of study participants reported recent drug use and 20 % reported recent homelessness. At baseline, the median CD4 cell count was 349 cells/ml and 18 % of eligible persons (CD4,350) took antiretroviral therapy (ART). Marginal structural models were used to estimate the population-level effects of behavioral, social, and structural factors on overall physical and mental health status (measured by the SF-36), and targeted variable importance (tVIM) was used to empirically rank factors by their influence. After adjusting for confounding, and in order of their influence, the three factors with the strongest negative effects on physical health were unmet subsistence needs, Caucasian race, and no reported source of instrumental support. The three factors with the strongest negative effects on mental health were unmet subsistence needs, not having a close friend/confidant, and drug use. ART adherence.90 % ranked 5th for its positive influence on mental health, and viral loa