CAPN5 genetic inactivation phenotype supports therapeutic inhibition trials

Small molecule pharmacological inhibition of dominant human genetic disease is a feasible treatment that does not rely on the development of individual, patient‐specific gene therapy vectors. However, the consequences of protein inhibition as a clinical therapeutic are not well‐studied. In advance of human therapeutic trials for CAPN5 vitreoretinopathy, genetic inactivation can be used to infer the effect of protein inhibition in vivo. We created a photoreceptor‐specific knockout (KO) mouse for Capn5 and compared the retinal phenotype to both wild‐type and an existing Capn5 KO mouse model. In humans, CAPN5 loss‐of‐function (LOF) gene variants were ascertained in large exome databases from 60,706 unrelated subjects without severe disease phenotypes. Ocular examination of the retina of Capn5 KO mice by histology and electroretinography showed no significant abnormalities. In humans, there were 22 LOF CAPN5 variants located throughout the gene and in all major protein domains. Structural modeling of coding variants showed these LOF variants were nearby known disease‐causing variants within the proteolytic core and in regions of high homology between human CAPN5 and 150 homologs, yet the LOF of CAPN5 was tolerated as opposed to gain‐of‐function disease‐causing variants. These results indicate that localized inhibition of CAPN5 is a viable strategy for hyperactivating disease alleles.     

Identification of cultivable microorganisms from primary endodontic infections with exposed and unexposed pulp space

This study was aimed at comparing the cultivable microorganisms in canals with periapical radiolucencies with exposed and unexposed pulp space. Microbiological samples were taken and analyzed from 45 canals with exposed pulp space, and 43 canals with unexposed pulp space. The canal contents were analyzed by aerobic/anaerobic culture, and conventional identification techniques. There were 211 isolates of bacteria belonging to 28 genera and 55 species recovered from exposed canals. In the unexposed group, 185 isolates of bacteria were recovered, of which 54 species of 28 genera were identified. Among the four most common genera, Prevotella was significantly more common in the exposed group (51/211 in the exposed group versus 30/185 in the unexposed group) (p = 0.049), while there were no differences in prevalence of Actinomyces, Peptostreptococcus, and Campylobacter between two groups of canals. In addition, Fusobacterium nucleatum and Propionibacterium acne were significantly more common in the unexposed canals (p = 0.047 and p = 0.0051, respectively). Similarity in bacterial species in these two groups suggests that pulp space exposure may not be a significant factor in determining the type of bacteria present in infected canals.     

Dental caries and chemical warfare within the mouth

To date, it appears that the dentists' war against dental caries has no end in sight due to the fact that dentists lack any genuine offensive firepower. Make no mistake, the defense has drastically improved as dentists have shifted the focus more toward the preventive aspects of dental care. But defense by itself cannot defeat the enemy; at best, it can maintain the status quo. In order to defeat the enemy, one must study and understand the enemy, to know its strengths and weaknesses, and to strike at those points of vulnerability. The aim of this research is to identify and characterize genes that are responsible for observed virulence factors in Streptococcus mutans, which is the primary pathogen involved in the development of dental caries. Once there is a more defined understanding of the many virulence factors of S. mutans, there will be a much more valuable insight into its role in the ecology of the oral cavity. Eventually, this knowledge could enable dentists to convert the bacterial "weaponry" into its own arsenal, which could then be innovatively employed as preventive, diagnostic, and therapeutic agents to treat oral bacterial-related diseases.     

Compound composite odontome associated with impacted canine. Case report

A case of compound composite odontome is reported. The classification and aetiology of odontomes is briefly discussed.     

Heterogeneity in antifungal susceptibility of clones of Candida albicans isolated on single and sequential visits from a HIV-infected southern Chinese cohort

The increased frequency and severity of candidal infections in human immunodeficiency virus (HIV)-infected individuals has prompted the wide use of antifungals, such as amphotericin B, ketoconazole, and fluconazole, resulting in the emergence of drug-resistant strains of Candida albicans. To study this phenomenon in an ethnic Chinese cohort, we isolated multiple colonies of Candida from the oral cavities of 16 HIV-infected patients on single and subsequent sequential visits over a period of 12 months. Ten of the 16 patients had sporadic episodes of oropharyngeal candidiasis (Group A), while the remainder were asymptomatic with respect to this condition (Group B). Oral rinses were collected and immediately processed in the laboratory for the isolation of C. albicans in a standard manner. A total of 433 C. albicans isolates were tested for their susceptibility to amphotericin B, ketoconazole and fluconazole by an agar diffusion method using the commercially available E-test. All tested isolates demonstrated variable susceptibility to amphotericin B, ketoconazole and fluconazole. The minimum inhibitory concentration (MIC) of the isolates for amphotericin B, ketoconazole and fluconazole ranged from <0.002-1.5 microg/ml, <0.002-4.0 microg/ml and <0.016-32 microg/ml, respectively. Sequential isolates of a few patients demonstrated variable susceptibility to all the antifungals, and no discernible MIC pattern emerged either in group A or B over time. Interestingly, significant variation in antifungal susceptibility was also noted in isolates obtained from the same patient on a single visit. Sequential yeast isolates in 9 of 16 patients (56%) demonstrated significant differences in MIC within and between visits for both amphotericin B and ketoconazole, while a lower percentage--44%(7/16)--exhibited this trait for fluconazole. Our study demonstrates the diversity in antifungal susceptibility in either commensal or "infective" oral strains of C. albicans in HIV disease, and shows the need for vigilance for the emergence of resistant strains, and for frequent antifungal susceptibility studies.     

Sleep disturbances in 22q11.2 deletion syndrome: a case with obstructive and central sleep apnea.

The 22q11.2 deletion syndrome is characterized by wide phenotypic variability, frequently involving characteristic craniofacial features, cardiac malformations, and learning difficulties. Skeletal anomalies are also common and include an obtuse angle of the cranial base, retrognathia, and cervical spine abnormalities. Despite these anomalies, sleep-disturbed breathing is not reported frequently in patients with 22q11.2 deletion syndrome. We describe a patient with an obstructive sleep disturbance that was successfully treated with a tonsillectomy followed by mandibular distraction osteogenesis. She also had central sleep apnea, initially attributed to spinal cord impingement from cervical instability. Posterior cervical fusion was associated with a decrease in the number of central apneic events.     

New scaphocephaly severity indices of sagittal craniosynostosis: a comparative study with cranial index quantifications.

OBJECTIVE: To describe a novel set of scaphocephaly severity indices (SSIs) for predicting and quantifying head- and skull-shape deformity in children diagnosed with isolated sagittal synostosis (ISS) and compare their sensitivity and specificity with those of the traditional cranial index (CI). METHODS: Computed tomography head scans were obtained from 60 patients diagnosed with ISS and 41 age-matched control patients. Volumetric reformations of the skull and overlying skin were used to trace two-dimensional planes defined in terms of skull-base plane and internal or surface landmarks. For each patient, novel SSIs were computed as the ratio of head width and length as measured on each of these planes. A traditional CI was also calculated and a receiver operating characteristic curve analysis was applied to compare the sensitivity and specificity of the proposed indices with those of CI. RESULTS: Although the CI is a sensitive measure of scaphocephaly, it is not specific and therefore not a suitable predictor of ISS in many practical applications. The SSI-A provides a specificity of 95% at a sensitivity level of 98%, in contrast with the 68% of CI. On average, the sensitivity and specificity of all proposed indices are superior to those of CI. CONCLUSIONS: Measurements of cranial width and length derived from planes that are defined in terms of internal or surface landmarks and skull-base plane produce SSIs that outperform traditional CI measurements.     

Comparison of cephalometric analysis using a non-radiographic sonic digitizer (DigiGraph Workstation) with conventional radiography

Cephalometric analysis conventionally requires radiographic exposure which may not be compatible with the growing concern over radiation hazards. Recently, the Dolphin Workstation Imaging System introduced to the dental profession a non-radiographic system, called the DigiGraph Workstation which may be an alternative to cephalometric radiography. The aims of this study were to compare the validity and reproducibility of cephalometric measurements obtained from the DigiGraph Workstation with conventional cephalometric radiographs. The sample consisted of 30 human dry skulls. Two replicated sets of lateral cephalograms were obtained with steel ball markers placed at the majority of the cephalometric landmarks. Duplicate tracings prepared from each radiograph were digitized to obtain cephalometric measurements using the computer software, Dentofacial Planner. For the DigiGraph Workstation, double sonic digitizations were repeated twice for each skull, on two occasions. Fifteen angular and one linear measurements were obtained from both methods and these findings compared using ANOVA, paired t-tests and F-tests. All, except one, cephalometric measurement showed significant differences between the two methods (P < 0.0001). The DigiGraph Workstation consistently produced higher values in 11 measurements (mean differences +0.5 to +15.7 degrees or mm) and lower values in four measurements (mean differences -0.2 to -3.5 degrees). The standard deviations of the differences between readings of both methods were large (0.4-5.8 degrees or mm). The reproducibility of the DigiGraph Workstation measurements was lower than that of the radiographic measurements. The method error of the DigiGraph Workstation ranged from 7 to 70 per cent, while that of radiographic tracings was less than 2 per cent. It was concluded that measurements obtained with the DigiGraph Workstation should be interpreted with caution.