Reproducibility of electrical caries measurements: A technical problem?

The currently available instrument for electrical detection of occlusal caries lesions {[}Electronic Caries Monitor (ECM)] uses a site-specific measurement with co-axial air drying. The reproducibility of this method has been reported to be fair to good. It was noticed that the measurement variation of this technique appeared to be non-random. It was the aim of this study to analyse how such a non-random reproducibility pattern arises and whether it could be observed for other operators and ECM models. Analysis of hypothetical measurement pairs showed that the pattern was related to measurements at the high and low end of the measurement range for the instrument. Data sets supplied by other researchers to a varying degree showed signs of a similar non-random pattern. These data sets were acquired at different locations, by different operators and using 3 different ECM models. The frequency distribution of measurements in all cases showed a single or double end-peaked distribution shape. It was concluded that the pattern was a general feature of the measurement method. It was tentatively attributed to several characteristics such as a high value censoring, insufficient probe contact and unpredictable probe contact. A different measurement technique, with an improved probe contact, appears to be advisable. Copyright (C) 2005 S. Karger AG, Basel

Disease relevance of rare VPS13B missense variants for neurodevelopmental Cohen syndrome

Autosomal recessive Cohen syndrome is a neurodevelopmental disorder characterized by postnatal microcephaly, intellectual disability, and a typical facial gestalt. Genetic variants in VPS13B have been found to cause Cohen syndrome, but have also been linked to autism, retinal disease, primary immunodeficiency, and short stature. While it is well established that loss-of-function mutations of VPS13B cause Cohen syndrome, the relevance of missense variants for the pathomechanism remains unexplained. Here, we investigate their pathogenic effect through a systematic re-evaluation of clinical patient information, comprehensive in silico predictions, and in vitro testing of previously published missense variants. In vitro analysis of 10 subcloned VPS13B missense variants resulted in full-length proteins after transient overexpression. 6/10 VPS13B missense variants show reduced accumulation at the Golgi complex in the steady state. The overexpression of these 6/10 VPS13B missense variants did not rescue the Golgi fragmentation after the RNAi-mediated depletion of endogenous VPS13B. These results thus validate 6/10 missense variants as likely pathogenic according to the classification of the American College of Medical Genetics through the integration of clinical, genetic, in silico, and experimental data. In summary, we state that exact variant classification should be the first step towards elucidating the pathomechanisms of genetically inherited neuronal diseases

Left ventricular noncompaction in children: the role of genetics, morphology, and function for outcome

Left ventricular noncompaction (LVNC) is a ventricular wall anomaly morphologically characterized by numerous, excessively prominent trabeculations and deep intertrabecular recesses. Accumulating data now suggest that LVNC is a distinct phenotype but must not constitute a pathological phenotype. Some individuals fulfill the morphologic criteria of LVNC and are without clinical manifestations. Most importantly, morphologic criteria for LVNC are insufficient to diagnose patients with an associated cardiomyopathy (CMP). Genetic testing has become relevant to establish a diagnosis associated with CMP, congenital heart disease, neuromuscular disease, inborn error of metabolism, or syndromic disorder. Genetic factors play a more decisive role in children than in adults and severe courses of LVNC tend to occur in childhood. We reviewed the current literature and highlight the difficulties in establishing the correct diagnosis for children with LVNC. Novel insights show that the interplay of genetics, morphology, and function determine the outcome in pediatric LVNC

Effects of dental probing on occlusal surfaces - A scanning electron microscopy evaluation

The aim of this clinical-morphological study was to investigate the effects of dental probing on occlusal surfaces by scanning electron microscopy (SEM). Twenty sound occlusal surfaces of third molars and 20 teeth with initial carious lesions of 17- to 26-year-old patients (n = 18) were involved. Ten molars of each group were probed with a sharp dental probe (No. 23) before extraction; the other molars served as negative controls. After extraction of the teeth, the crowns were separated and prepared for the SEM study. Probing-related surface defects, enlargements and break-offs of occlusal pits and fissures were observed on all occlusal surfaces with initial carious lesions and on 2 sound surfaces, respectively. No traumatic defects whatsoever were visible on unprobed occlusal surfaces. This investigation confirms findings of light-microscopic studies that using a sharp dental probe for occlusal caries detection causes enamel defects. Therefore, dental probing should be considered as an inappropriate procedure and should be replaced by a meticulous visual inspection. Critical views of tactile caries detection methods with a sharp dental probe as a diagnostic tool seem to be inevitable in undergraduate and postgraduate dental education programmes. Copyright (c) 2007 S. Karger AG, Basel

An in vitro comparison between two methods of electrical resistance measurement for occlusal caries detection

Because of different measurement techniques and the easier design of the CRM prototype, this in vitro study aimed to compare the diagnostic performance and reproducibility of two electrical methods (Electronic Caries Monitor III, ECM and Cariometer 800, CRM) for occlusal caries detection, and to evaluate the effect of staining/ discoloration of fissures on diagnostic performance. Hundred and seventeen third molars with no apparent occlusal cavitation were selected. Six examiners inspected all specimens independently, using the CRM, and a subgroup of 4 using the ECM. Histological validation using a stereomicroscope was performed after hemisectioning. Intra- and interexaminer reproducibility was assessed by Lin's concordance correlation coefficient (CCC) and Bland and Altman analysis. Diagnostic performance parameters included sensitivity (SE), specificity (SP) and area under the ROC curve (A(z)). The CCC yielded an intra- and interexaminer reproducibility of 0.69/0.62 (ECM) and of 0.79/0.74 (CRM). The mean intra- and interexaminer 95% range of measurements (range between Bland and Altman limits of agreement) given in percentages of the instrument reading were 67%/65% for the ECM and 28%/33% for the CRM. A(z) at the D3-4 level was 0.74 (ECM) and 0.78 (CRM). The CRM showed at least equivalent diagnostic performance to the ECM. However, improvement is still desirable. Diagnostic performance appeared to be enhanced in discolored lesions; however, this may be related to sample lesion distribution characteristics. Copyright (C) 2006 S. Karger AG, Basel

Somatic neurofibromatosis type 1 (NF1) inactivation events in cutaneous neurofibromas of a single NF1 patient

Neurofibromatosis type 1 (NF1) (MIM#162200) is a relatively frequent genetic condition that predisposes to tumor formation. The main types of tumors occurring in NF1 patients are cutaneous and subcutaneous neurofibromas, plexiform neurofibromas, optic pathway gliomas, and malignant peripheral nerve sheath tumors. To search for somatic mutations in cutaneous (dermal) neurofibromas, whole-exome sequencing (WES) was performed on seven spatially separated tumors and two reference tissues (blood and unaffected skin) from a single NF1 patient. Validation of WES findings was done using routine Sanger sequencing or Sequenom IPlex SNP genotyping. Exome sequencing confirmed the existence of a known familial splice-site mutation NM_000267.3:c.3113+1G>A in exon 23 of NF1 gene (HGMD ID CS951480) in blood, unaffected skin, and all tumor samples. In five out of seven analyzed tumors, we additionally detected second-hit mutations in the NF1 gene. Four of them were novel and one was previously observed. Each mutation was distinct, demonstrating the independent origin of each tumor. Only in two of seven tumors we detected an additional somatic mutation that was not associated with NF1. Our study demonstrated that somatic mutations of NF1 are likely the main drivers of cutaneous tumor formation. The study provides evidence for the rareness of single base pair level alterations in the exomes of benign NF1 cutaneous tumors.European Journal of Human Genetics advance online publication, 8 October 2014; doi:10.1038/ejhg.2014.210

Midwall fibrosis and cardiac mechanics: rigid body rotation is a novel marker of disease severity in pediatric primary dilated cardiomyopathy

BACKGROUND: Midwall fibrosis (MWF) detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) predicts adverse outcome in adults with dilated cardiomyopathy (DCM). Its relevance in children and adolescents is relatively unknown. Left ventricular (LV) strain, rotation and twist are important parameters of cardiac function; yet, their role in pediatric heart failure is understudied. This study aimed to evaluate MWF and cardiac mechanics in pediatric DCM. METHODS: Patients ≤21 years with primary DCM were prospectively enrolled and underwent standardized CMR including LGE. All participants were categorized according to the presence or absence of MWF (MWF+ vs. MWF–). Cardiac mechanics were assessed using CMR feature tracking. Impaired LV twist with apex and base rotating in the same direction was termed rigid body rotation (RBR). RESULTS: In total, 17 patients (median age 11.2 years) were included. MWF was present in seven patients (41%). Median N-terminal pro brain natriuretic peptide (NT-proBNP) was higher (5,959 vs. 242 pg/ml, p = 0.887) and LV ejection fraction (LVEF) lower (28 vs. 39%, p = 0.536) in MWF+ vs. MWF– patients, yet differences were not statistically significant. MWF+ patients had reduced global longitudinal (GLS), circumferential (GCS) and radial strain (GRS), again without statistical significance (p = 0.713, 0.492 and 1.000, respectively). A relationship between MWF and adverse outcome was not seen (p = 0.637). RBR was more common in MWF+ (67 vs. 50%), and was associated with the occurrence of adverse events (p = 0.041). Patients with RBR more frequently were in higher New York Heart Association classes (p = 0.035), had elevated NT-proBNP levels (p = 0.002) and higher need for catecholamines (p = 0.001). RBR was related to reduced GLS (p = 0.008), GCS (p = 0.031), GRS (p = 0.012), LV twist (p = 0.008), peak apical rotation (p < 0.001), and LVEF (p = 0.001), elevated LV end-diastolic volume (p = 0.023) and LV end-systolic volume (p = 0.003), and lower right ventricular stroke volume (p = 0.023). CONCLUSIONS: MWF was common, but failed to predict heart failure. RBR was associated with clinical and biventricular functional signs of heart failure as well as the occurrence of adverse events. Our findings suggest that RBR may predict outcomes and may serve as a novel marker of disease severity in pediatric DCM. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, identifier: NCT03572569

Comparison of four different treatment strategies in teeth with molar-incisor hypomineralization-related enamel breakdown–A retrospective cohort study

Background There is little information available on the longevity of non-invasive glass ionomer cement (GIC) and composite restorations as well as conventional composite and ceramic restorations placed on permanent teeth with enamel breakdowns due to molar-incisor hypomineralization (MIH). Aim To compare the longevity of the abovementioned treatment procedures. Design Of 377 identified MIH patients, 118 individuals received restorative treatment and were invited for clinical examination, including caries and MIH status. Finally, survival data from 204 MIH-related restorations placed on 127 teeth were retrospectively collected from 52 children, monitored between 2010 and 2018. Descriptive and explorative analyses were performed, including Kaplan-Meier estimators and the Cox regression model. Results The mean patient observation time was 42.9 months (SD = 35.1). The cumulative survival probabilities after 36 months—7.0% (GIC, N = 28), 29.9% (non-invasive composite restoration, N = 126), 76.2% (conventional composite restoration, N = 27) and 100.0% (ceramic restoration, N = 23)—differed significantly in the regression analysis. Conclusions Conventional restorations were associated with moderate-to-high survival rates in MIH teeth. In contrast, non-invasive composite restorations, which were predominately used in younger or less cooperative children, were linked to lower survival rates

The diagnostic accuracy of a laser fluorescence device and digital radiography in detecting approximal caries lesions in posterior permanent teeth: an in vivo study

The aim of this in vivo study was to test the diagnostic accuracy of a pen-type laser fluorescence (LFpen) device in detecting approximal caries lesions, in posterior permanent teeth, at the cavitation and non-cavitation thresholds, and compare it with that of digital bitewing radiography. Thirty patients (aged 18–37), who attended the Faculty of Dentistry at Damascus University for a dental examination, were consecutively screened. Ninety approximal surfaces of posterior permanent teeth without frank cavitations, enamel hypoplasia or restorations were selected and examined using the LFpen (DIAGNOdent pen) and digital bitewing radiography. The reference standard was the visual-tactile inspection, after performing temporary tooth separation, using orthodontic rubber rings, placed for 7 days. The status of included approximal surfaces was recorded as intact/sound, with white/brown spots or cavitated. One trained examiner performed all examinations. There were statistically significant differences in LFpen readings between the three types of approximal surface status (P < 0.001). The optimal cut-off values for detecting approximal caries lesions in posterior permanent teeth were >16 and 8 at the cavitation and non-cavitation thresholds respectively. The sensitivity, specificity and accuracy (measured by the area under the receiver-operating characteristic curve) were 100, 85 and 95 and 92, 90 and 95% at the cavitation and non-cavitation thresholds respectively. The intra-class correlation coefficient for intra-examiner reliability was 0.95. The diagnostic accuracy of the LFpen was significantly higher than that of digital bitewing radiography (P < 0.001). The LFpen’s diagnostic performance was accurate and significantly better than digital bitewing radiography in detecting approximal caries lesions, in posterior permanent teeth. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10103-017-2157-2) contains supplementary material, which is available to authorized users