Stress as a determinant of saliva-mediated adherence and coadherence of oral and nonoral microorganisms

Objective:: The mucosal secretory proteins, such as the salivary proteins, play a key role in the acquisition and regulation of the mucosal microflora. Most notably, some microorganisms utilize the host's secretory proteins to adhere to the mucosa; a first step in colonization and infection. The secretory proteins also influence colonization by affecting the binding among microorganisms, a process denoted as coadherence. Previously we reported that acute stressors cause specific changes in saliva composition. The present study investigated to what extent these changes influence saliva-mediated microbial adherence and coadherence (ex vivo). Methods:: Thirty-two male undergraduates provided unstimulated saliva before and during a control condition and two stressors: A memory test and a surgery video presentation. We used saliva-coated microplates to test the adherence of bacteria for which the oral cavity is either a natural reservoir (eg, viridans streptococci) or a portal of entry (eg, Helicobacter pylori). We also tested the saliva-mediated co-adherence between Streptococcus gordonii and the yeast Candida albicans. Correlation analyses were performed to determine the relationships between changes in microbial adherence and the concentrations of potential salivary ligands, viz. cystatin S, the mucins MUC5B and MUC7, S-IgA, lactoferrin, [alpha]-amylase, and total salivary protein. Results:: During the memory test, saliva-mediated adhesion of Streptococcus sanguis, Streptococcus gordonii, and H. pylori increased, whereas the coadherence of C. albicans with S. gordonii decreased. During the surgical video presentation the saliva-mediated adherence of H. pylori, S. sanguis, and Streptococcus mitis increased. These changes were independent of salivary flow rate, but correlated with specific changes in salivary protein composition. Conclusion:: The results show that even moderate stressors, by altering the activity of the mucosal secretory glands, may affect microbial colonization processes such as adherence and coadherence. This study hereby presents a mechanism by which stress may affect the mucosal microflora and susceptibility to infectious disease

Integration of IRF6 and Jagged2 signalling is essential for controlling palatal adhesion and fusion competence

In mammals, adhesion and fusion of the palatal shelves are essential mechanisms during the development of the secondary palate; failure of these processes leads to the congenital anomaly, cleft palate. The mechanisms that prevent pathological adhesion between the oral and palatal epithelia while permitting adhesion and subsequent fusion of the palatal shelves via their medial edge epithelia remain obscure. In humans, mutations in the transcription factor interferon regulatory factor 6 (IRF6) underlie Van der Woude syndrome and popliteal pterygium syndrome. Recently, we have demonstrated that mice homozygous for a mutation in Irf6 exhibit abnormalities of epithelial differentiation that results in cleft palate as a consequence of adhesion between the palatal shelves and the tongue. In the current paper, we demonstrate that Irf6 is essential for oral epithelial differentiation and that IRF6 and the Notch ligand Jagged2 function in convergent molecular pathways during this process. We further demonstrate that IRF6 plays a key role in the formation and maintenance of the oral periderm, spatio-temporal regulation of which is essential for ensuring appropriate palatal adhesion

Missense mutations that cause Van der Woude syndrome and popliteal pterygium syndrome affect the DNA-binding and transcriptional activation functions of IRF6

Cleft lip and cleft palate (CLP) are common disorders that occur either as part of a syndrome, where structures other than the lip and palate are affected, or in the absence of other anomalies. Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) are autosomal dominant disorders characterized by combinations of cleft lip, CLP, lip pits, skin-folds, syndactyly and oral adhesions which arise as the result of mutations in interferon regulatory factor 6 (IRF6). IRF6 belongs to a family of transcription factors that share a highly conserved N-terminal, DNA-binding domain and a less well-conserved protein-binding domain. To date, mutation analyses have suggested a broad genotype–phenotype correlation in which missense and nonsense mutations occurring throughout IRF6 may cause VWS; in contrast, PPS-causing mutations are highly associated with the DNA-binding domain, and appear to preferentially affect residues that are predicted to interact directly with the DNA. Nevertheless, this genotype–phenotype correlation is based on the analysis of structural models rather than on the investigation of the DNA-binding properties of IRF6. Moreover, the effects of mutations in the protein interaction domain have not been analysed. In the current investigation, we have determined the sequence to which IRF6 binds and used this sequence to analyse the effect of VWS- and PPS-associated mutations in the DNA-binding domain of IRF6. In addition, we have demonstrated that IRF6 functions as a co-operative transcriptional activator and that mutations in the protein interaction domain of IRF6 disrupt this activity

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

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

Signs and symptoms of temporomandibular disorders and oral parafunctions in urban Saudi arabian adolescents: a research report

BACKGROUND: The aim of this study was to evaluate the prevalence of signs and symptoms of temporomandibular disorders (TMD) and oral parafunction habits among Saudi adolescents in the permanent dentition stage. METHODS: A total of 385 (230 females and 155 males) school children age 12–16, completed a questionnaire and were examined clinically. A stratified selection technique was used for schools allocation. RESULTS: The results showed that 21.3% of the subjects exhibited at least one sign of TMD and females were generally more affected than males. Joint sounds were the most prevalent sign (13.5%) followed by restricted opening (4.7%) and opening deviation (3.9%). The amplitude of mouth opening, overbite taken into consideration, was 46.5 mm and 50.2 mm in females and males respectively. TMJ pain and muscle tenderness were rare (0.5%). Reported symptoms were 33%, headache being the most frequent symptom 22%, followed by pain during chewing 14% and hearing TMJ noises 8.7%. Difficulty during jaw opening and jaw locking were rare. Lip/cheek biting was the most common parafunction habit (41%) with females significantly more than males, followed by nail biting (29%). Bruxism and thumb sucking were only 7.4% and 7.8% respectively. CONCLUSION: The prevalence of TMD signs were 21.3% with joint sounds being the most prevalent sign. While TMD symptoms were found to be 33% as, with headache being the most prevalent. Among the oral parafunctions, lip/cheek biting was the most prevalent 41% followed by nail biting 29%

Developmental, genetic, and environmental components of lung volumes at high altitude

Vital capacity and residual lung volume (in terms of 1/min or ml/m 2 of body surface area) of 357 subjects (205 males, 152 females) was evaluated in La Paz, Bolivia, situated at 3,750 m. The sample included: (1) 37 high altitude rural natives (all male), (2) 125 high altitude urban natives (69 male, 58 female), (3) 85 Bolivians of foreign ancestry acclimatized to high altitude since birth (40 male, 45 female), (4) 63 Bolivians of foreign ancestry acclimatized to high altitude during growth (30 male, 33 female), and (5) 47 non-Bolivians of either European or North American ancestry acclimatized to high altitude during adulthood (24 male, 23 female). Results indicate that (1) all samples studied, irrespective of origin or acclimatization status, have larger lung volumes than those predicted from sea level norms; (2) the high altitude rural natives have significantly greater lung volumes (vital capacity and residual lung volume) than the high altitude urban natives and all the non-native high altitude samples; (3) males acclimatized to high altitude since birth or during growth attain similar lung volumes as high altitude urban natives and higher residual lung volumes than subjects acclimatized to high altitude during adulthood but lower than the high altitude rural natives; (4) females acclimatized to high altitude since birth or during growth attain similar lung volumes as subjects acclimatized to high altitude during adulthood; (5) age at arrival to high altitude is inversely related to residual lung volume but not vital capacity; (6) among subjects acclimatized to high altitude during growth, approximately 20–25% of the variability in residual lung volume can be explained by developmental factors; (7) among high altitude rural and urban natives, it appears that approximately 20–25% of the variability in residual lung volume at high altitude can be explained by genetic traits associated with skin reflectance and genetic traits shared by siblings; and (8) vital capacity, but not the residual lung volume, is inversely related to occupational activity level. Together these data suggest that the attainment of vital capacity at high altitude is influenced more by environmental factors, such as occupational activity level, and body composition than developmental acclimatization. On the other hand, the attainment of an enlarged residual volume is related to both developmental acclimatization and genetic factors. Am. J. Hum. Biol. 9:191–203, 1997. © 1997 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38564/1/5_ftp.pd