Selective vs stepwise removal of deep carious lesions in primary molars: 24 months follow-up from a randomized controlled trial.

OBJECTIVES: For well-defined deep (> 2/3 dentin extension) carious lesions, selective (SE) or stepwise (SW) carious tissue removals have been recommended, while there is limited comparative evidence for both. We compared SE and SW over 24 months in a randomized controlled trial. METHODS: A two-arm superiority trial was conducted comparing SW/SE in primary molars without pulpal symptoms but well-defined deep lesions. Seventy-four children (1 molar/child) aged 3-9 years were recruited. In a first step, peripheral carious tissue was removed until hard dentin remained, while in proximity to the pulp, leathery dentin was left. An adhesive compomer restoration was placed and restorations re-examined after 6 months. In SW, re-entry and removal to firm dentin was conducted pulpo-proximally, followed by re-restoration. Molars were re-evaluated for a total of 24 months. Our primary outcome was success (absence of restorative/endodontic complications or pulp exposures). Secondary outcomes included total treatment and opportunity costs and restoration quality, assessed using modified USPHS criteria. RESULTS: After 24 months, 63 molars (31 SE, 32 SW) were re-assessed. Four failures occurred (2 exposures in SW; 2 pulpal complications in SE, 1 of them leading to extraction, p > 0.05). Restoration integrity was satisfying in both groups (USPHS A/B/C in 21/8/0 SE and 23/7/0 SW, p > 0.05). Treatment and opportunity costs were significantly higher in SW than SE (mean 171 ± 51 vs. 106 ± 90; p < 0.001). CONCLUSIONS: After 2 years, SE and SW showed similar efficacy for managing deep carious lesions in primary molars. The higher costs for SW should be considered during decision-making. CLINICAL SIGNIFICANCE: In primary molars with well-defined deep carious lesions SE was less costly and similarly efficacious like SW. From a cost and applicability perspective, SW may need to be indicated restrictively, e.g., for very deep (> 3/4 dentin extension) lesions only. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02232828.

Selective vs stepwise removal of deep carious lesions in primary molars: 12-Months results of a randomized controlled pilot trial.

OBJECTIVES: For deep carious lesions, selective or stepwise carious tissue removal (SE, SW) seem advantageous compared with non-selective removal. For primary molars, there is insufficient evidence comparing SE against SW. This randomized pilot trial compared SE and SW over 12 months. METHODS: A two-arm superiority trial was conducted comparing SE and SW in primary molars with deep lesions but without pulpal symptoms. We recruited 74 children (one molar/child) aged 3-9 years. In both groups, peripheral carious tissue removal was performed at T1 to hard dentin. In proximity to the pulp, leathery dentin was left followed by an adhesive compomer restoration. Blinded re-examination was performed after six months (T2). Molars allocated to SW were re-entered, removal to firm dentin carried out pulpo-proximally, and again restored. After another 6 months, all molars were re-examined (T3). Our primary outcome was success, defined as no restorative/endodontic complications (including pulp exposure) leading to reinterventions. Secondary outcomes included total treatment and opportunity costs. Patients', dentists' and parents' subjective assessments were recorded. This trial was registered (ClinicalTrials.gov/NCT02232828). RESULTS: After 12 months a total of 72 children (36 SE, 36 SW) were analyzed. Three failures occurred (2 exposures in SW, 1 pulpal complication leading to extraction in SE) (p > 0.05). The subjective evaluation by patients, parents or dentists did not differ significantly. Combined treatment and opportunity costs were significantly higher in SW (mean;SD: 186;61 Euro) than SE (100;59) (p < 0.001). CONCLUSIONS: The significantly increased costs for performing SW instead of SE in deep carious lesions in primary molars may not be justified. CLINICAL SIGNIFICANCE: For primary molars with deep lesions, but vital pulps, SE was less costly at similar efficacy compared with SW. Dentists' decision-making should consider this alongside further clinical aspects.

Oral manifestations, dental management, and a rare homozygous mutation of the PRDM12 gene in a boy with hereditary sensory and autonomic neuropathy type VIII: a case report and review of the literature.

BACKGROUND: Hereditary sensory and autonomic neuropathy type VIII is a rare autosomal recessive inherited disorder. Chen et al. recently identified the causative gene and characterized biallelic mutations in the PR domain-containing protein 12 gene, which plays a role in the development of pain-sensing nerve cells. Our patient's family was included in Chen and colleagues' study. We performed a literature review of the PubMed library (January 1985 to December 2016) on hereditary sensory and autonomic neuropathy type I to VIII genetic disorders and their orofacial manifestations. This case report is the first to describe the oral manifestations, and their treatment, of the recently discovered hereditary sensory and autonomic neuropathy type VIII in the medical and dental literature. CASE PRESENTATION: We report on the oral manifestations and dental management of an 8-month-old white boy with hereditary sensory and autonomic neuropathy-VIII over a period of 16 years. Our patient was homozygous for a mutation of PR domain-containing protein 12 gene and was characterized by insensitivity to pain and thermal stimuli, self-mutilation behavior, reduced sweat and tear production, absence of corneal reflexes, and multiple skin and bone infections. Oral manifestations included premature loss of teeth, associated with dental traumata and self-mutilation, severe soft tissue injuries, dental caries and submucosal abscesses, hypomineralization of primary teeth, and mandibular osteomyelitis. CONCLUSIONS: The lack of scientific knowledge on hereditary sensory and autonomic neuropathy due to the rarity of the disease often results in a delay in diagnosis, which is of substantial importance for the prevention of many complications and symptoms. Interdisciplinary work of specialized medical and dental teams and development of a standardized treatment protocols are essential for the management of the disease. There are many knowledge gaps concerning the management of patients with hereditary sensory and autonomic neuropathy-VIII, therefore more research on an international basis is needed.

Drugs related to the etiology of molar incisor hypomineralization: A systematic review.

BACKGROUND: Molar incisor hypomineralization (MIH) is an idiopathic syndrome that has been associated with several etiologic factors. The authors' objective was to systematically review studies in which the investigators had studied how the etiology of MIH was related to medication intake. TYPES OF STUDIES REVIEWED: The search covered a period from January 1, 1965, to September 29, 2014. The search revealed 1,042 articles, to which the authors applied eligibility criteria and selected 20 studies for review. The authors considered 9 of the 20 studies to be high quality. The drugs used in these studies were chemotherapeutic drugs, antibiotics, asthma drugs, antiepileptic drugs, antiviral drugs, antifungal drugs, and antiparasitic drugs. RESULTS: Two reviewers independently performed risk-of-bias assessment and data extraction. The investigators of all of the studies had reported enamel defects, but only 2 sets of investigators had used the term "molar incisor hypomineralization." Owing to the different methodologies used by the investigators of the selected studies, the authors could not perform a meta-analysis of the study results. CONCLUSIONS: More well-designed prospective studies are needed to clarify the relationship between MIH and medication. PRACTICAL IMPLICATIONS: It would be convenient to establish a preventive protocol in patients with a potential risk of developing MIH to avoid the complications that are characteristic of this disease.

Transcriptional regulator PRDM12 is essential for human pain perception.

Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families. Prdm proteins are a family of epigenetic regulators that control neural specification and neurogenesis. We determined that Prdm12 is expressed in nociceptors and their progenitors and participates in the development of sensory neurons in Xenopus embryos. Moreover, CIP-associated mutants abrogate the histone-modifying potential associated with wild-type Prdm12. Prdm12 emerges as a key factor in the orchestration of sensory neurogenesis and may hold promise as a target for new pain therapeutics.

Selective or stepwise removal of deep caries in deciduous molars: study protocol for a randomized controlled trial.

BACKGROUND: For treating deep caries lesions, selective or stepwise (one- and two-step) incomplete excavation seems advantageous compared with complete caries removal. However, current evidence regarding the success, as defined by not requiring any retreatments, or survival of teeth after different excavations is insufficient for definitive recommendation, especially when treating deciduous teeth. Moreover, restoration integrity has not been comparatively analyzed longitudinally, and neither patients', dentists' or parents' preferences nor the clinical long-term costs emanating from both initial and retreatments have been reported yet. METHODS/DESIGN: The planned study is a prospective multicenter, two-arm parallel group, randomized controlled clinical trial comparing selective and stepwise excavation in deciduous molars with deep, active caries lesions without pulpal symptoms. We will recruit 300 children aged between three and nine-years-old with a minimum of one such molar. Patients participating in another study, or those with systemic diseases, disabilities or known allergies to used materials as well patients with teeth expected to exfoliate within the next 18 months will be excluded. After inclusion, sequence generation will be performed. Initial treatment will follow dental routine. During excavation, leathery, moist and reasonably soft dentin will be left in proximity to the pulp followed by adhesive restoration of the cavity. Afterwards, patients', dentists' and parents' subjective assessment of the treatment will be recorded using visual analogue or Likert scales. Re-examination will be performed after six months, and only then teeth will be allocated to one of the two interventions. Selectively excavated teeth will not be treated further, whilst for stepwise caries removal, a second excavation will be performed until only hard dentin remains. Clinical re-evaluations will be performed after 12, 24 and 36 months. Restorations will be reassessed using modified Ryge criteria. Objectively or subjectively required retreatments will determine success and survival. Retreatments will be evaluated both subjectively and regarding generated costs. DISCUSSION: Based on the results of the trial, decision-making for treating deep caries lesions in deciduous molars based on multiple criteria should be feasible. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02232828 (registered on 29 November 2014).

Multidisciplinary treatment options of tooth avulsion considering different therapy concepts.

BACKGROUND: Avulsion of permanent front teeth is a rare accident, mostly affecting children between seven and nine years of age. Replanted and splinted, these teeth often develop inflammation, severe resorption or ankylosis affecting alveolar bone development and have to be extracted sooner or later. OBJECTIVES: The purpose of this study was to evaluate different therapy concepts to create a structured concept for the treatment of avulsions. RESULTS: Based on existing therapy concepts, a concept for different initial conditions (dry time, age, growth, tooth, hard and soft tissues) was developed and is presented here. CONCLUSION: A great deal of research has been performed during recent years and guidelines for the management of avulsions have been published. With the help of this literature it is possible to identify the best treatment procedure for each tooth. CLINICAL RELEVANCE: The prognosis of avulsed teeth can be improved by considering evidence-based therapy concepts. Resorption, ankylosis and tooth loss could be minimized.

Effects of air-polishing devices with different abrasives on bovine primary and second teeth and deciduous human teeth.

OBJECTIVE: The present study investigates the effect of air polishing using different combinations of devices and abrasive powders on bovine secondary and primary dentition and on human deciduous teeth. MATERIALS AND METHODS: Lower incisors of freshly slaughtered calves and cows were partially embedded in polyurethane and polished flat. Human deciduous incisors and second molars were subjected to the same procedure. These various tooth types (bovine secondary, bovine primary, human deciduous) were then randomly assigned to 22 groups containing 10 teeth each. The specimens in each group were treated by a specific combination of an air-polishing device (n=2; PROPHYflex 3®, Air-Flow® Handy 2+) and an abrasive (n=3; Air-Flow® Pulver Classic, ClinPro™ Prophy Powder, PROPHYpearls®) applied from a distance of 5±0.5 mm at maximum setting for 60 s. Additional groups of specimens were polished with CCS® 40 or Cleanic® pastes applied with a rotating brush at low speed. A Perthometer PCV profilometer was used to analyze the degrees of surface roughness and enamel reduction in each group. RESULTS: PROPHYpearls® created significantly (p<0.05; t-test) more surface roughness and enamel reduction than both Air-Flow® and ClinPro™. There was no significant difference between the latter two abrasives. Any surface changes created by blasting or polishing were significantly (p<0.05; t-test) smaller on the bovine secondary teeth than on bovine primary or human deciduous teeth, with no significant difference between the latter two. The degrees of surface roughness induced by air polishing surpassed the effect of CCS® 40 paste but resembled the effect of Cleanic® paste. CONCLUSION: Both Air-Flow® Handy 2+ and PROPHYflex 3® are appropriate devices to remove plaque and discoloration from the surface of deciduous teeth. PROPHYpearls® powder is excessively aggressive.

Modeling neuronal activity in relation to experimental voltage-/patch-clamp recordings.

A mechanism-based, Hodgkin-Huxley-type modeling approach is proposed that allows connecting the key parameters of experimental voltage-/patch-clamp data directly to the major control values of the model. The objective of this paper is to facilitate the use of mathematical modeling in supplement to electrophysiological recordings. Typical recordings from current-clamp, whole-cell voltage-clamp, and single-channel patch-clamp experiments are illustrated by means of a simplified computer model designed for life science education. These examples demonstrate that the "rate constants", on which the original Hodgkin-Huxley equations are built up, are difficult, in most experiments even impossible, to extract from experimental data. As the combination of the two exponential rate constants leads to sigmoid activation curves, they can be replaced by sigmoid voltage dependencies, mostly presented in form of Boltzmann functions. Conversely, connecting whole-cell and single-channel patch-clamp simulations, the Boltzmann functions, can be related to exponentially voltage dependent probability factors of ion channel transition rates. The thereby introduced small variability of the activation values suggests that the power functions of the activation variables in the current equations can be neglected. Eliminating the rate constants and the power functions can be physiologically justified and makes the model easier to handle, especially in context with experimental data. Further possibilities of dimension reduction as well as model extensions are discussed. This article is part of a Special Issue entitled Neural Coding 2012.

Noise-induced precursors of tonic-to-bursting transitions in hypothalamic neurons and in a conductance-based model.

The dynamics of neurons is characterized by a variety of different spiking patterns in response to external stimuli. One of the most important transitions in neuronal response patterns is the transition from tonic firing to burst discharges, i.e., when the neuronal activity changes from single spikes to the grouping of spikes. An increased number of interspike-interval sequences of specific temporal correlations was detected in anticipation of temperature induced tonic-to-bursting transitions in both, experimental impulse recordings from hypothalamic brain slices and numerical simulations of a stochastic model. Analysis of the modelling data elucidates that the appearance of such patterns can be related to particular system dynamics in the vicinity of the period-doubling bifurcation. It leads to a nonlinear response on de- and hyperpolarizing perturbations introduced by noise. This explains why such particular patterns can be found as reliable precursors of the neurons' transition to burst discharges.

Temperature-dependent stochastic dynamics of the Huber-Braun neuron model.

The response of a four-dimensional mammalian cold receptor model to different implementations of noise is studied across a wide temperature range. It is observed that for noisy activation kinetics, the parameter range decomposes into two regions in which the system reacts qualitatively completely different to small perturbations through noise, and these regions are separated by a homoclinic bifurcation. Noise implemented as an additional current yields a substantially different system response at low temperature values, while the response at high temperatures is comparable to activation-kinetic noise. We elucidate how this phenomenon can be understood in terms of state space dynamics and gives quantitative results on the statistics of interspike interval distributions across the relevant parameter range.

On the role of subthreshold currents in the Huber-Braun cold receptor model.

We study the role of the strength of subthreshold currents in a four-dimensional Hodgkin-Huxley-type model of mammalian cold receptors. Since a total diminution of subthreshold activity corresponds to a decomposition of the model into a slow, subthreshold, and a fast, spiking subsystem, we first elucidate their respective dynamics separately and draw conclusions about their role for the generation of different spiking patterns. These results motivate a numerical bifurcation analysis of the effect of varying the strength of subthreshold currents, which is done by varying a suitable control parameter. We work out the key mechanisms which can be attributed to subthreshold activity and furthermore elucidate the dynamical backbone of different activity patterns generated by this model.

A computational study of the interdependencies between neuronal impulse pattern, noise effects and synchronization.

Alterations of individual neurons dynamics and associated changes of the activity pattern, especially the transition from tonic firing (single-spikes) to bursts discharges (impulse groups), play an important role for neuronal information processing and synchronization in many physiological processes (sensory encoding, information binding, hormone release, sleep-wake cycles) as well as in disease (Parkinson, epilepsy). We have used Hodgkin-Huxley-type model neurons with subthreshold oscillations to examine the impact of noise on neuronal encoding and thereby have seen significant differences depending on noise implementation as well as on the neuron's dynamic state. The importance of the individual neurons' dynamics is further elucidated by simulation studies with electrotonically coupled model neurons which revealed mutual interdependencies between the alterations of the network's coupling strength and neurons' activity patterns with regard to synchronization. Remarkably, a pacemaker-like activity pattern which revealed to be much more noise sensitive than the bursting patterns also requires much higher coupling strengths for synchronization. This seemingly simple pattern is obviously governed by more complex dynamics than expected from a conventional pacemaker which may explain why neurons more easily synchronize in the bursting than in the tonic firing mode.

Propagation effects of current and conductance noise in a model neuron with subthreshold oscillations.

We have examined the effects of current and conductance noise in a single-neuron model which can generate a variety of physiologically important impulse patterns. Current noise enters the membrane equation directly while conductance noise is propagated through the activation variables. Additive Gaussian white noise which is implemented as conductance noise appears in the voltage equations as an additive and a multiplicative term. Moreover, the originally white noise is turned into colored noise. The noise correlation time is a function of the system's control parameters which may explain the different effects of current and conductance noise in different dynamic states. We have found the most significant, qualitative differences between different noise implementations in a pacemaker-like, tonic firing regime at the transition to chaotic burst discharges. This reflects a dynamic state of high physiological relevance.

Dental findings in patients with ectodermal dysplasia.

BACKGROUND: Ectodermal dysplasia is an inherited disease causing malformations of all tissues originating from the ectoderm. The significance of this disease lies in severe hypodontia, and an accompanying hypoplasia of the alveolar process. The clinical situation is aggravated by a significant xerostomia. It was the aim of this study to document the distribution of hypodontia and tooth malformation. Furthermore, we aimed to elucidate the clinical impact of these findings. PATIENTS AND METHODS: Records of 30 patients (19 males, 11 females) suffering from ectodermal dysplasia were included. Their age ranged between 7 and 23 years. All patients had been examined clinically and radiographically. In every patient, a record was made of which teeth were missing or malformed, and which deciduous teeth persisted. Additionally, the entire treatment procedure was assessed. RESULTS: The third molars were missing in all of the patients. The number of aplastic permanent teeth ranged from 2 to 26. The maxillary lateral incisors were most frequently absent, followed by the mandibular central incisors. The most stable teeth were the central incisors of the upper jaw, and the canines and first molars in both jaws. However, the maxillary central incisors and canines were the teeth most affected by malformation. Deciduous canines and second molars were the most often persisting teeth due to agenesis of the maxillary lateral permanent incisors and mandibular second premolars. In two-thirds of the patients, missing teeth were replaced by removable dentures. Half of the patients received orthodontic treatment. CONCLUSIONS: Hypodontia and malformation are almost regular dental characteristics in patients suffering from ectodermal dysplasia. The distribution of absent teeth deviates remarkably from the general population. Treatment requires an interdisciplinary approach including orthodontics, prosthodontics and oral surgery.