Mouth development

WIREs Developmental Biology published by Wiley Periodicals, Inc. A mouth is present in all animals, and comprises an opening from the outside into the oral cavity and the beginnings of the digestive tract to allow eating. This review focuses on the earliest steps in mouth formation. In the first half, we conclude that the mouth arose once during evolution. In all animals, the mouth forms from ectoderm and endoderm. A direct association of oral ectoderm and digestive endoderm is present even in triploblastic animals, and in chordates, this region is known as the extreme anterior domain (EAD). Further support for a single origin of the mouth is a conserved set of genes that form a ‘mouth gene program’ including foxA and otx2. In the second half of this review, we discuss steps involved in vertebrate mouth formation, using the frog Xenopus as a model. The vertebrate mouth derives from oral ectoderm from the anterior neural ridge, pharyngeal endoderm and cranial neural crest (NC). Vertebrates form a mouth by breaking through the body covering in a precise sequence including specification of EAD ectoderm and endoderm as well as NC, formation of a ‘pre-mouth array,’ basement membrane dissolution, stomodeum formation, and buccopharyngeal membrane perforation. In Xenopus, the EAD is also a craniofacial organizer that guides NC, while reciprocally, the NC signals to the EAD to elicit its morphogenesis into a pre-mouth array. Human mouth anomalies are prevalent and are affected by genetic and environmental factors, with understanding guided in part by use of animal models.National Institute of Dental and Craniofacial Research (U.S.) (Grant RO1 DE021109

A defect in early myogenesis causes Otitis media in two mouse models of 22q11.2 Deletion Syndrome

Otitis media (OM), the inflammation of the middle ear, is the most common disease and cause for surgery in infants worldwide. Chronic Otitis media with effusion (OME) often leads to conductive hearing loss and is a common feature of a number of craniofacial syndromes, such as 22q11.2 Deletion Syndrome (22q11.2DS). OM is more common in children because the more horizontal position of the Eustachian tube (ET) in infants limits or delays clearance of middle ear effusions. Some mouse models with OM have shown alterations in the morphology and angle of the ET. Here, we present a novel mechanism in which OM is caused not by a defect in the ET itself but in the muscles that control its function. Our results show that in two mouse models of 22q11.2DS (Df1/+ and Tbx1(+/-)) presenting with bi- or unilateral OME, the fourth pharyngeal arch-derived levator veli palatini muscles were hypoplastic, which was associated with an earlier altered pattern of MyoD expression. Importantly, in mice with unilateral OME, the side with the inflammation was associated with significantly smaller muscles than the contralateral unaffected ear. Functional tests examining ET patency confirmed a reduced clearing ability in the heterozygous mice. Our findings are also of clinical relevance as targeting hypoplastic muscles might present a novel preventative measure for reducing the high rates of OM in 22q11.2DS patients

Epidemic spread of ST1-MRSA-IVa in a neonatal intensive care unit, Italy.

BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has recently emerged as an important pathogen in neonatal intensive care units (NICUs). The purposes of this study were to characterize methicillin-resistant isolates from an outbreak in a NICU, to examine the genetic traits and clonality of CA-MRSA, and to review the characteristics and outcomes of the neonatal cases and investigate the routes of entry and transmission of the MRSA outbreak strain in the NICU under study. METHODS: The study NICU practiced an active surveillance program for multidrug-resistant organisms, including weekly cultures for detection of MRSA from nasal swabs among all the admitted neonates. All first isolates from surveillance cultures and all clinical isolates were submitted for susceptibility testing and genotyping. Data from each infant’s medical records were prospectively included in a database, and the clinical features and outcomes of the colonized/infected infants were assessed. RESULTS: A total of 14 infants were colonized or infected by a strain of ST1-MRSA-IVa between April and August 2011. The CA-MRSA strain appeared to have been introduced to the NICU by an infected infant transferred from another hospital. The outbreak was successfully contained by multifaceted infection control interventions. CONCLUSIONS: The results of this study confirm that NICU is a healthcare setting with a critical permeability to CA-MRSA. Active surveillance including molecular typing can help to detect and monitor the spread of antimicrobial drug-resistant organisms, and thus trigger timely control interventions

Cystic fibrosis mice carrying the missense mutation G551D replicate human genotype phenotype correlations

We have generated a mouse carrying the human G551D mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR) by a one-step gene targeting procedure. These mutant mice show cystic fibrosis pathology but have a reduced risk of fatal intestinal blockage compared with 'null' mutants, in keeping with the reduced incidence of meconium ileus in G551D patients. The G551D mutant mice show greatly reduced CFTR-related chloride transport, displaying activity intermediate between that of cftr(mlUNC) replacement ('null') and cftr(mlHGU) insertional (residual activity) mutants and equivalent to approximately 4% of wild-type CFTR activity. The long-term survival of these animals should provide an excellent model with which to study cystic fibrosis, and they illustrate the value of mouse models carrying relevant mutations for examining genotype-phenotype correlations

Dysphonia secondary to traumatic avulsion of the vocal fold in infants

Objective: Airway compromise due to paediatric intubation injuries is well documented; however, intubation injuries may also cause severe voice disorders. We report our experience and review the world literature on the voice effects of traumatic paediatric intubation. Case series: We report five cases of children referred to Great Ormond Street Hospital for Children who suffered traumatic avulsion of the vocal fold at the time of, or secondary to, endotracheal intubation. All children had significant dysphonia and underwent specialist voice therapy. Conclusions: The mechanisms of injury, risk factors and management of the condition are discussed. Children suffering traumatic intubation require follow up throughout childhood and beyond puberty as their vocal needs and abilities change. At the time of writing, none of the reported patients had yet undergone reconstructive or medialisation surgery. However, regular specialist voice therapy evaluation is recommended for such patients, with consideration of phonosurgical techniques including injection laryngoplasty or thyroplasty

The effect of posture in premature infants on the arterial oxygen saturation, fraction of inspired oxygen and abdominal distension

Background: Putting infants in a posture that reduces oxygen requirement and the complications of the continuous positive airway pressure method is very important. This study aimed at examining the effect of the posture on the arterial oxygen saturation, fraction of inspired oxygen (FIO2) and abdominal distension in premature infants with the respiratory distress syndrome under nasal continuous positive airway pressure. Materials and Methods: In this clinical trial study, 41 premature infants were selected by the simple random sampling and one-group before-after design. The amounts of arterial oxygen saturation, FIO2 and abdominal distension in supine and prone positions were recorded in a data-collection form. Results: There was a significant difference between the mean FIO2 and between the mean abdominal circumference in the prone and supine positions (P=0.022, P<0.001, respectively). There was no significant difference in the mean of arterial oxygen saturation between the two positions (P=0.749). Conclusion: According to the results of the present study, the neonates’ abdominal distension and FIO2 decreased in the prone position. Thus, this supportive, free of charge and effective method can be recommended for these neonates