Impact of dental restorations and removable prostheses on potentially malignant oral mucosal disorders in the general population.

STATEMENT OF PROBLEM: Dental restorations and removable dental prostheses have been considered as risk factors for potentially malignant disorders of the oral mucosa. It remains unclear whether amalgam, composite resins, and prosthesis materials can induce potentially malignant disorders. PURPOSE: The purpose of this clinical study was to determine the relationship between the presence of amalgam and composite resin restorations, crowns and fixed partial dentures, and removable prostheses in potentially malignant disorders. MATERIAL AND METHODS: The data of 6041 participants in the population-based Studies of Health in Pomerania (SHIP) were accessed. Potentially malignant disorders had been clinically diagnosed by calibrated dentists and documented with photographs. Dental treatment was subdivided into restored and replaced teeth. Dental restorations were subclassified as buccal composite resin or amalgam restorations. Prosthetic treatment was subclassified into removable partial or complete prostheses and definitive restorations with crowns and fixed partial dentures. RESULTS: In the maxilla, participants with removable prostheses had a higher incidence of potentially malignant disorders than participants not undergoing treatment with removable prostheses (OR 2.12; 95% CI: 1.08-4.18), but not in the mandible (OR 1.30; 95% CI: 0.67-2.53). The surfaces with composite resin restorations were associated with a slightly higher risk of mucosal lesions than those without the restorations (OR 1.04; 95% CI: 1.01-1.07). No significant association was found between amalgam restorations and mucosal lesions. CONCLUSIONS: Participants with removable prostheses have a higher risk of potentially malignant disorders. Composite resin restorations are associated with a higher risk of mucosal lesions, whereas no significant association was found between amalgam restorations and mucosal lesions.

Prevalence and risk factors of potentially malignant disorders of the mucosa in the general population: Mucosa lesions a general health problem?

AIM: Oral cancer mostly develops from oral mucosa regions with morphological alterations transforming malignant. These visible precancerous mucosa lesions are named potentially malignant disorders (PMD). We aimed to analyze the prevalence of PMD and its risk factors for PMD in a population-based sample in Northern Germany. MATERIAL AND METHODS: Data of 6078 individuals from the population-based Study of Health in Pomerania (SHIP) was used. PMD were photographically documented and periodontal health was assessed in a standardized procedure. RESULTS: PMD were observed in 54 individuals (0.9%). The most prevalent PMD was homogenous leukoplakia (n = 37) followed by Lichen ruber (n = 9). Smoking (Odds Ratio (OR) 2.70; 95% confidence interval (CI): 1.24-5.87), male sex (OR 3.32; 95%-CI: 1.77-6.21), type 2 diabetes mellitus (OR 2.07; 95%-CI: 1.08-3.98) and body mass index (OR 1.09; CI 1.04-1.14) were significantly associated with PMD, with the corresponding area under the curve (AUC) being 0.696 (CI: 0.655; 0.737). CONCLUSION: Our results suggest a clinically relevant prevalence of PMD in the population. We identified male sex, type 2 diabetes mellitus, current smoking, and obesity as risk factors. We recommend photographic documentation and intensified training of medical and dental staff to detect and monitor PMD.

Do Third Molars Contribute to Systemic Inflammation? Results From a Population-Based Study From Northeast Germany.

PURPOSE: Erupted and impacted third molars have been reported to contribute to systemic inflammation. This study investigated the systemic effect of third molars on serum levels of inflammatory parameters and on inflammatory messenger peptide hormones in a general population sample. MATERIALS AND METHODS: Data of 2,151 participants from the Study of Health in Pomerania were included in this study. Erupted or impacted third molars were assessed with whole-body magnetic resonance imaging at 1.5 T and associated with biomarkers of inflammation, lipid metabolism, glucose metabolism, and peptide hormones by linear regression. Models were adjusted for age, gender, smoking status, education, and type 2 diabetes mellitus. RESULTS: Neither erupted nor impacted third molars were associated with high-sensitivity C-reactive protein, white blood cell count, or fibrinogen as markers for systemic inflammation. Participants with erupted third molars had markedly lower serum levels of leptin (ß coefficient, -2.47; 95% confidence interval [CI], -4.47 to -0.48), angiopoietin-2 (ß coefficient, -135.1; 95% CI, 248.6 to -21.5), and ratio of angiopoietin-2 to tyrosine kinase with immunoglobulin-like loop epidermal growth factor homology domain 2 (ß coefficient, -6.57; 95% CI, -13.06 to -00.7) than participants without third molars. No such associations were observed for impacted third molars. CONCLUSION: The present results did not substantiate a relation between third molars and an increase in systemic inflammatory markers. Therefore, dental practitioners should be careful when considering this as the only indication for removal of third molars, especially in medically compromised patients. The results of this study showed that participants with erupted third molars had lower levels of messenger peptide hormones, such as leptin and angiopoetin-2.

New insights in the link between malocclusion and periodontal disease.

AIM: We aimed to investigate associations between malocclusions and periodontal disease by comparing it to that of smoking in subjects recruited from the population-based cross-sectional study "Study of Health in Pomerania." MATERIALS AND METHODS: Sagittal intermaxillary relationship, variables of malocclusion and socio-demographic parameters of 1,202 dentate subjects, 20-39 years of age, were selected. Probing depth (PD) and attachment loss (AL) were assessed at four sites by tooth in a half-mouth design. Analyses were performed with multilevel models on subject, jaw and tooth level. RESULTS: Distal occlusion determined in the canine region, ectopic position of canines, anterior spacing, deep anterior overbite and increased sagittal overjet were associated with AL (p-value <0.05). Associations between malocclusions and PD: deep anterior overbite with gingival contact (odds ratio [OR] = 1.40, 95% CI: 1.08-1.82; p-value = 0.0101) and anterior crossbite (OR = 1.75, 95% CI: 1.29-2.38; p-value = 0.0003). Regarding crowding, only severe anterior crowding was compatible with a moderate to large association with PD (OR = 1.93, 95% CI: 0.89-4.20). Compared to smoking, the overall effect of malocclusions was about one half for AL and one-third for PD. CONCLUSION: Malocclusions or morphologic parameters were associated with periodontal disease.

De Novo Missense Mutations in DHX30 Impair Global Translation and Cause a Neurodevelopmental Disorder.

DHX30 is a member of the family of DExH-box helicases, which use ATP hydrolysis to unwind RNA secondary structures. Here we identified six different de novo missense mutations in DHX30 in twelve unrelated individuals affected by global developmental delay (GDD), intellectual disability (ID), severe speech impairment and gait abnormalities. While four mutations are recurrent, two are unique with one affecting the codon of one recurrent mutation. All amino acid changes are located within highly conserved helicase motifs and were found to either impair ATPase activity or RNA recognition in different in vitro assays. Moreover, protein variants exhibit an increased propensity to trigger stress granule (SG) formation resulting in global translation inhibition. Thus, our findings highlight the prominent role of translation control in development and function of the central nervous system and also provide molecular insight into how DHX30 dysfunction might cause a neurodevelopmental disorder.

Triterpenes for Well-Balanced Scar Formation in Superficial Wounds.

Triterpenes are demonstrably effective for accelerating re-epithelialisation of wounds and known to improve scar formation for superficial lesions. Among the variety of triterpenes, betuline is of particular medical interest. Topical betuline gel (TBG) received drug approval in 2016 from the European Commission as the first topical therapeutic agent with the proven clinical benefit of accelerating wound healing. Two self-conducted randomized intra-individual comparison clinical studies with a total of 220 patients involved in TBG treatment of skin graft surgical wounds have been screened for data concerning the aesthetic aspect of wound healing. Three months after surgery wound treatment with TBG resulted in about 30% of cases with more discreet scars, and standard of care in about 10%. Patients themselves appreciate the results of TBG after 3 months even more (about 50%) compared to standard of care (about 10%). One year after surgery, the superiority of TBG counts for about 25% in comparison with about 10%, and from the patients' point of view, for 25% compared to 4% under standard of care. In the majority of wound treatment cases, there is no difference visible between TBG treatment and standard of care after 1 year of scar formation. However, in comparison, TBG still offers a better chance for discreet scars and therefore happens to be superior in good care of wounds.

Impact of depressive symptoms on prosthetic status--results of the study of health in Pomerania (SHIP).

OBJECTIVES: Previous investigations have confirmed that every fifth dental patient suffers from clinically significant depressive symptoms. However, the putative impact of depressive symptoms on the prosthetic status has not been addressed in these studies. The objective of this study was to investigate the association between depressive symptoms and prosthetic status based on data from the Study of Health in Pomerania (SHIP-0). METHODS: Data from 2,135 participants aged 30 to 59 years were analyzed. A classification (six classes regarding the number and position of missing teeth per jaw) was used to identify the degree of prosthetic status (no/suboptimal/optimal tooth replacement). The presence of depressive symptoms was assessed with a modified version of von Zerssen's complaints scale. Screening for lifetime diagnoses of mental disorders was performed with the Composite International Diagnostic-Screener (CID-S). Multivariable logistic regressions including several confounders were calculated. RESULTS: A significant protective dose-response effect of depressive symptoms on prosthetic status was found only in men for the lower jaw [0-1 depressive symptoms: odds ratio (OR) = 3.84, 95 % confidence interval (CI, 1.65-8.92), p < 0.01; 2-3: OR = 2.87 (CI, 1.22-6.74), p < 0.05; reference, ≥8; adjusted for age, school education, smoking status, household income, marital status, living without a partner, risky alcohol consumption, obesity, diabetes, and physical activity]. There was no such association in women or for the upper jaw. The analyses using the CID-S confirmed these results. CONCLUSIONS: In the lower jaw, men with depressive symptoms had a better prosthetic status than men without depressive symptoms suggesting a higher level of concern regarding their personal health. CLINICAL RELEVANCE: If dentists might have an opportunity to identify men with depressive symptoms they can provide a wide range of treatment options that may enhance patients' self-esteem and contribute to the patient' well-being. Furthermore, depressive symptoms could indicate a discrepancy between self-perception of the dental health and the actual status which influence the dentists' treatment decision making.

Synthesis of two SAPAP3 isoforms from a single mRNA is mediated via alternative translational initiation.

In mammalian neurons, targeting and translation of specific mRNAs in dendrites contribute to synaptic plasticity. After nuclear export, mRNAs designated for dendritic transport are generally assumed to be translationally dormant and activity of individual synapses may locally trigger their extrasomatic translation. We show that the long, GC-rich 5'-untranslated region of dendritic SAPAP3 mRNA restricts translation initiation via a mechanism that involves an upstream open reading frame (uORF). In addition, the uORF enables the use of an alternative translation start site, permitting synthesis of two SAPAP3 isoforms from a single mRNA. While both isoforms progressively accumulate at postsynaptic densities during early rat brain development, their levels relative to each other vary in different adult rat brain areas. Thus, alternative translation initiation events appear to regulate relative expression of distinct SAPAP3 isoforms in different brain regions, which may function to influence synaptic plasticity.

Refining definitions of periodontal disease and caries for prediction models of incident tooth loss.

AIM: To assess the suitability of different definitions of caries and periodontitis for inclusion in tooth loss prediction models. MATERIALS AND METHODS: The Study of Health in Pomerania (SHIP) is a population-based cohort study conducted in 1997-2001 (SHIP-0) and 2002-2006 (SHIP-1). This sample comprised 2,780 subjects aged 20-81 years with complete information on dental and periodontal status [DMFS status, clinical attachment loss (CAL) and probing depth (PD)]. Analyses on five-year tooth loss were limited to half-mouth data. RESULTS: The predictive value of tested definitions was markedly age- and gender-dependent: in 20-39-aged men, the number of decayed or filled surfaces best predicted the number of lost teeth, whereas in young women CAL≥4 mm performed best. In older subjects, periodontal definitions were superior to caries definitions: mean CAL performed best in 40-59-year olds, whereas AL- or PD-related definitions predicted best in 60-81-year olds. On tooth level, mean CAL was the superior definition to assess 5-year incident tooth loss in all strata except for young men. CONCLUSIONS: Caries parameters best predicted incident tooth loss in men aged 20-39 years; in the intermediate and oldest age group and in young women, mean AL was most informative. Therefore, prediction models need to be developed for different age and gender groups.

Inositol-1,4,5-trisphosphate 3-kinase A regulates dendritic morphology and shapes synaptic Ca2+ transients.

Inositol-1,4,5-trisphosphate 3-kinase-A (itpka) accumulates in dendritic spines and seems to be critically involved in synaptic plasticity. The protein possesses two functional activities: it phosphorylates inositol-1,4,5-trisphosphate (Ins(1,4,5)P(3)) and regulates actin dynamics by its F-actin bundling activity. To assess the relevance of these activities for neuronal physiology, we examined the effects of altered itpka levels on cell morphology, Ins(1,4,5)P(3) metabolism and dendritic Ca(2+) signaling in hippocampal neurons. Overexpression of itpka increased the number of dendritic protrusions by 71% in immature primary neurons. In mature neurons, however, the effect of itpka overexpression on formation of dendritic spines was weaker and depletion of itpka did not alter spine density and synaptic contacts. In synaptosomes of mature neurons itpka loss resulted in decreased duration of Ins(1,4,5)P(3) signals and shorter Ins(1,4,5)P(3)-dependent Ca(2+) transients. At synapses of itpka deficient neurons the levels of Ins(1,4,5)P(3)-5-phosphatase (inpp5a) and sarcoplasmic/endoplasmic reticulum calcium ATPase pump-2b (serca2b) were increased, indicating that decreased duration of Ins(1,4,5)P(3) and Ca(2+) signals results from compensatory up-regulation of these proteins. Taken together, our data suggest a dual role for itpka. In developing neurons itpka has a morphogenic effect on dendrites, while the kinase appears to play a key role in shaping Ca(2+) transients at mature synapses.

Mutations in TOPORS: a rare cause of autosomal dominant retinitis pigmentosa in continental Europe?

Mutations in TOPORS cause autosomal dominant retinitis pigmentosa (adRP). Examination of 160 adRP patients from continental Europe revealed nine exonic single nucleotide variants, eight of which reside in the coding region; three synonymous single nucleotide polymorphisms (SNPs; c.2319T > C, c.2991T > C and c.1560A > G), three nonsynonymous SNPs (c.58C > T/p.P20S, c.74C >G/p.S25W and c.1730C > A/p.S577Y) and two novel missense mutations (c.1205A > C/p.Q402P and c.1818T > G/p.S606R). Whether the latter two variants represent adRP causing mutations awaits further analysis.

Occupational exposure to ionizing radiation is associated with autoimmune thyroid disease.

CONTEXT: The thyroid gland is a potential target organ for radiation-related damage. OBJECTIVE: The aim of the analysis was to investigate the association between occupational exposure to ionizing radiation and autoimmune thyroid disease (AITD). DESIGN: Our design was the cross-sectional Study of Health in Pomerania. SETTING: The setting was the general community. SUBJECTS: Analyses were performed in a population-based sample of 4299 subjects. Among them, 160 persons reported a history of occupational exposure to ionizing radiation. MAIN OUTCOME MEASURE: AITD was defined as the combined presence of hypoechogenicity in thyroid ultrasound and antithyroxiperoxidase antibodies greater than 200 IU/ml. RESULTS: Females with occupational exposure to ionizing radiation had more often AITD than nonexposed females (10.0 vs. 3.4%; P < 0.05). This association persisted after adjustment for relevant confounders (odds ratio, 3.46; 95% confidence interval, 1.16-10.31; P < 0.05). In males, there were too few subjects who fulfilled the criteria of AITD, but the association between the exposure to radiation and hypoechogenicity of the thyroid gland barely missed statistical significance (odds ratio, 2.20; 95% confidence interval, 0.92-5.26; P = 0.08). In both females and males, subjects who reported a length of exposure of more than 5 yr exhibited the highest risk of the endpoints. CONCLUSIONS: We conclude that occupational exposure to ionizing radiation is related to the risk of AITD. The usage of thyroid protection shields by radiation workers is strongly recommended.