Finite Element Analysis of Fixed Orthodontic Retainers.

The efficacy of retainers is a pivotal concern in orthodontic care. This study examined the biomechanical behaviour of retainers, particularly the influence of retainer stiffness and tooth resilience on force transmission and stress distribution. To do this, a finite element model was created of the lower jaw from the left to the right canine with a retainer attached on the oral side. Three levels of tooth resilience and variable retainer bending stiffness (influenced by retainer type, retainer diameter, and retainer material) were simulated. Applying axial or oblique (45° tilt) loads on a central incisor, the force transmission increased from 2% to 65% with increasing tooth resilience and retainer stiffness. Additionally, a smaller retainer diameter reduced the uniformity of the stress distribution in the bonding interfaces, causing concentrated stress peaks within a small field of the bonding area. An increase in retainer stiffness and in tooth resilience as well as a more oblique load direction all lead to higher overall stress in the adhesive bonding area associated with a higher risk of retainer bonding failure. Therefore, it might be recommended to avoid the use of retainers that are excessively stiff, especially in cases with high tooth resilience.

Tooth mobility restriction by multistranded and CAD/CAM retainers-an in vitro study.

OBJECTIVES: Orthodontic retainers should restrict physiological tooth mobility as little as possible. While this has been investigated for multistranded retainers, there is a lack of data for novel CAD/CAM retainers. To address this, the present study compared the restriction of physiological tooth mobility in multistranded retainers and different CAD/CAM retainers. MATERIAL/METHODS: One group of multistranded (n = 8) and five groups of CAD/CAM retainers (nickel-titanium (NiTi), titanium grade 5 (Ti5), polyetheretherketone (PEEK), zirconia (ZrO2), and cobalt-chromium (CoCr); each n = 8) bonded from canine to canine were investigated for their influence on vertical and horizontal tooth mobility using an in vitro model of a lower arch in a universal testing machine. Load-deflection curves were determined and statistically analysed. RESULTS: All retainers restricted tooth mobility to varying extents. The retainers had less of an influence on vertical tooth mobility, with less of a difference between retainers (14%-38% restriction). In contrast, significant (P ≤ 0.05) differences were observed between retainers in the restriction of horizontal tooth mobility. ZrO2 retainers had the greatest impact, restricting horizontal tooth mobility by 82% (68 ± 20 µm/100N), followed by CoCr (75%, 94 ± 26 µm/100N) and PEEK (73%, 103 ± 28 µm/100N) CAD/CAM retainers, which had comparable effects on horizontal tooth mobility. Ti5 (54%, 175 ± 66 µm/100N) and NiTi (34%, 248 ± 119 µm/100N) CAD/CAM retainers had less of an influence on horizontal tooth mobility, and were comparable to multistranded retainers (44%, 211 ± 77 µm/100N). LIMITATIONS: This is an in vitro study, so clinical studies are needed to draw clinical conclusions. CONCLUSIONS: Multistranded and CAD/CAM retainers have different effects on tooth mobility in vitro. These effects should be further explored in future in vivo studies.

A new CAD/CAM tooth mobility simulating model for dental in vitro investigations.

OBJECTIVES: To validate a new tooth mobility simulating in vitro model for biomechanical tests of dental appliances and restorations. MATERIAL AND METHODS: Load-deflection curves for teeth in CAD/CAM models (n = 10/group, 6 teeth/model) of the anterior segment of a lower jaw with either low tooth mobility (LM) or high tooth mobility (HM) were recorded with a universal testing device and a Periotest device. All teeth were tested before and after different ageing protocols. Finally, vertical load capacity (Fmax) was tested in all teeth. RESULTS: At F = 100 N load, vertical/horizontal tooth deflections before ageing were 80 ± 10 µm/400 ± 40 µm for LM models and 130 ± 20 µm/610 ± 100 µm for HM models. Periotest values were 1.6 ± 1.4 for LM models and 5.5 ± 1.5 for HM models. These values were within the range of physiological tooth mobility. No visible damage occurred during ageing and simulated ageing had no significant effect on tooth mobility. Fmax values were 494 ± 67 N (LM) and 388 ± 95 N (HM). CONCLUSION: The model is practical, easy to manufacture and can reliably simulate tooth mobility. The model was also validated for long-term testing, so is suitable for investigating various dental appliances and restorations such as retainers, brackets, dental bridges or trauma splints. CLINICAL RELEVANCE: Using this in-vitro model for high standardised investigations of various dental appliances and restorations can protect patients from unnecessary burdens in trials and practice.

Influence of Individual Bracket Base Design on the Shear Bond Strength of In-Office 3D Printed Brackets-An In Vitro Study.

(1) Background: Novel high-performance polymers for medical 3D printing enable in-office manufacturing of fully customized brackets. Previous studies have investigated clinically relevant parameters such as manufacturing precision, torque transmission, and fracture stability. The aim of this study is to evaluate different design options of the bracket base concerning the adhesive bond between the bracket and tooth, measured as the shear bond strength (SBS) and maximum force (Fmax) according to DIN 13990. (2) Methods: Three different designs for printed bracket bases were compared with a conventional metal bracket (C). The following configurations were chosen for the base design: Matching of the base to the anatomy of the tooth surface, size of the cross-sectional area corresponding to the control group (C), and a micro- (A) and macro- (B) retentive design of the base surface. In addition, a group with a micro-retentive base (D) matched to the tooth surface and an increased size was studied. The groups were analyzed for SBS, Fmax, and adhesive remnant index (ARI). The Kruskal-Wallis test with a post hoc test (Dunn-Bonferroni) and Mann-Whitney U test were used for statistical analysis (significance level: p < 0.05). (3) Results: The values for SBS and Fmax were highest in C (SBS: 12.0 ± 3.8 MPa; Fmax: 115.7 ± 36.6 N). For the printed brackets, there were significant differences between A and B (A: SBS 8.8 ± 2.3 MPa, Fmax 84.7 ± 21.8 N; B: SBS 12.0 ± 2.1 MPa, Fmax 106.5 ± 20.7 N). Fmax was significantly different for A and D (D: Fmax 118.5 ± 22.8 N). The ARI score was highest for A and lowest for C. (4) Conclusions: This study shows that conventional brackets form a more stable bond with the tooth than the 3D-printed brackets. However, for successful clinical use, the shear bond strength of the printed brackets can be increased with a macro-retentive design and/or enlargement of the base.

Comparison of six different CAD/CAM retainers vs. the stainless steel twistflex retainer: an in vitro investigation of survival rate and stability.

PURPOSE: To compare failure rates and maximum load capacity (Fmax) of six different computer-aided design/computer-aided manufacturing (CAD/CAM) retainers with those of the hand-bent five-stranded stainless steel twistflex retainer. MATERIALS AND METHODS: Six groups (n = 8 per group) of commercially available CAD/CAM retainers (cobalt-chromium [CoCr], titanium grade 5 [Ti5], nickel-titanium [NiTi], zirconia [ZrO2], polyetheretherketone [PEEK], and gold) and twistflex retainers were tested for long-term sufficiency and for Fmax using a self-developed in vitro model. All retainer models underwent a simulated ageing process of about 15 years (1,200,000 chewing cycles with a force magnitude of 65 N at 45° followed by storage in water at 37 °C for 30 days). If retainers did not debond or break during ageing, their Fmax was determined in a universal testing machine. Data were statistically analysed using Kruskal-Wallis and Mann-Whitney U­tests. RESULTS: Twistflex retainers did not fail (0/8) during ageing and had the highest Fmax (445 N ± 51 N). Ti5 retainers were the only CAD/CAM retainers that also did not fail (0/8) and had similar Fmax values (374 N ± 62 N). All other CAD/CAM retainers had higher failure rates during ageing and significantly lower Fmax values (p < 0.01; ZrO2: 1/8, 168 N ± 52 N; gold: 3/8, 130 N ± 52 N; NiTi: 5/8, 162 N ± 132 N; CoCr: 6/8, 122 N ± 100 N; PEEK: 8/8, 65 ± 0 N). Failure was due to breakage in the NiTi retainers and debonding in all other retainers. CONCLUSION: Twistflex retainers remain the gold standard regarding biomechanical properties and long-term sufficiency. Of the CAD/CAM retainers tested, Ti5 retainers seem to be the most suitable alternative. In contrast, all other CAD/CAM retainers investigated in this study showed high failure rates and had significantly lower Fmax values.

Concept for the Treatment of Class III Anomalies with a Skeletally Anchored Appliance Fabricated in the CAD/CAM Process-The MIRA Appliance.

OBJECTIVE: Intermaxillary elastics, anchored skeletally, represent a promising concept for treatment in adolescent patients with skeletal Class III anomalies. A challenge in existing concepts is the survival rate of the miniscrews in the mandible or the invasiveness of the bone anchors. A novel concept, the mandibular interradicular anchor (MIRA) appliance, for improving skeletal anchorage in the mandible, will be presented and discussed. CLINICAL CASE: In a ten-year-old female patient with a moderate skeletal Class III, the novel MIRA concept, combined with maxillary protraction, was applied. This involved the use of a CAD/CAM-fabricated indirect skeletal anchorage appliance in the mandible, with interradicularly placed miniscrews distal to each canine (MIRA appliance), and a hybrid hyrax in the maxilla with paramedian placed miniscrews. The modified alt-RAMEC protocol involved an intermittent weekly activation for five weeks. Class III elastics were worn for a period of seven months. This was followed by alignment with a multi-bracket appliance. DISCUSSION: The cephalometric analysis before and after therapy shows an improvement of the Wits value (+3.8 mm), SNA (+5°), and ANB (+3°). Dentally, a transversal postdevelopment in the maxilla (+4 mm) and a labial tip of the maxillary (+3.4°) and mandibular anterior teeth (+4.7°) with gap formation is observed. CONCLUSION: The MIRA appliance represents a less invasive and esthetic alternative to the existing concepts, especially with two miniscrews in the mandible per side. In addition, MIRA can be selected for complex orthodontic tasks, such as molar uprighting and mesialization.

Precision of slot widths and torque transmission of in-office 3D printed brackets : An in vitro study.

PURPOSE: To investigate a novel in-office three-dimensionally (3D) printed polymer bracket regarding slot precision and torque transmission. METHODS: Based on a 0.022″ bracket system, stereolithography was used to manufacture brackets (N = 30) from a high-performance polymer that met Medical Device Regulation (MDR) IIa requirements. Conventional metal and ceramic brackets were used for comparison. Slot precision was determined using calibrated plug gages. Torque transmission was measured after artificial aging. Palatal and vestibular crown torques were measured from 0 to 20° using titanium-molybdenum (T) and stainless steel (S) wires (0.019â€³â€¯× 0.025″) in a biomechanical experimental setup. The Kruskal-Wallis test with post hoc test (Dunn-Bonferroni) was used for statistical analyses (significance level p < 0.05). RESULTS: The slot sizes of all three bracket groups were within the tolerance range according to DIN 13996 (ceramic [C]: 0.581 ± 0.003 mm; metal [M]: 0.6 ± 0.005 mm; polymer [P]: 0.581 ± 0.010 mm). The maximum torque values of all bracket-arch combinations were above the clinically relevant range of 5-20 Nmm (PS: 30 ± 8.6 Nmm; PT: 27.8 ± 14.2 Nmm; CS: 24 ± 5.6 Nmm; CT: 19.9 ± 3.8 Nmm; MS: 21.4 ± 6.7 Nmm; MT: 16.7 ± 4.6 Nmm). CONCLUSIONS: The novel, in-office manufactured polymer bracket showed comparable results to established bracket materials regarding slot precision and torque transmission. Given its high individualization possibilities as well as enabling an entire in-house supply chain, the novel polymer brackets bear high potential of future usage for orthodontic appliances.

Diagnostic compatibility of various fixed orthodontic retainers for head/neck MRI and dental MRI.

OBJECTIVES: To evaluate the diagnostic MRI compatibility of different fixed orthodontic retainers using a high-resolution 3D-sequence optimized for artifact reduction. MATERIALS AND METHODS: Maxillary and mandibular retainers made of five different materials were scanned in vitro and in vivo at 3 T MRI using an MSVAT-SPACE sequence. In vitro, artifact volumes were determined for all maxillary and mandibular retainers (AVmax; AVmand). In vivo, two independent observers quantified the extent of artifacts based on the visibility of 124 dental and non-dental landmarks using a five-point rating scale (1 = excellent, 2 = good, 3 = acceptable, 4 = poor, 5 = not visible). RESULTS: Rectangular-steel retainers caused the largest artifacts (AVmax/AVmand: 18,060/15,879 mm3) and considerable diagnostic impairment in vivo (mean landmark visibility score ± SD inside/outside the retainer areas: 4.8 ± 0.8/2.9 ± 1.6). Smaller, but diagnostically relevant artifacts were observed for twistflex steel retainers (437/6317 mm3, 3.1 ± 1.7/1.3 ± 0.7). All retainers made of precious-alloy materials produced only very small artifact volumes (titanium grade 1: 70/46 mm3, titanium grade 5: 47/35 mm3, gold: 23/21 mm3) without any impact on image quality in vivo (each retainer: visibility scores of 1.0 ± 0.0 for all landmarks inside and outside the retainer areas). CONCLUSIONS: In contrast to steel retainers, titanium and gold retainers are fully compatible for both head/neck and dental MRI when using MSVAT-SPACE. CLINICAL RELEVANCE: This study demonstrates that titanium and gold retainers do not impair the diagnostic quality of head/neck and dental MRI when applying an appropriate artifact-reduction technique. Steel retainers, however, are not suitable for dental MRI and can severely impair image quality in head/neck MRI of the oral cavity.

Fit of anterior restorations made of 3D-printed and milled zirconia: An in-vitro study.

OBJECTIVES: To evaluate the fit of zirconia veneers made by either 3D printing or milling. METHODS: A typodont maxillary central incisor was prepared for a 0.5-mm-thick veneer and was reproduced 36 times from resin. Restorations were designed with a 20-µm-wide marginal and a 60-µm-wide internal cement gap, and were made from 3D-printed zirconia (LithaCon 3Y 210, Lithoz, n = 24) and milled zirconia (Cercon ht, DentsplySirona, n = 12). For milled zirconia, a drill compensation was needed to give the milling bur access to the intaglio surface. The restorations were cemented, cross-sectioned, and the cement gap size was analyzed by two raters. Inter-rater reliability was studied at 12 3D-printed veneers (intraclass correlation coefficient, ICC, mixed model, absolute agreement). Twelve remaining 3D-printed restorations were compared with 12 milled restorations regarding fit at three locations: marginally, labially, and at the incisal edge (Mann-Whitney U-tests, α<0.05). RESULTS: Inter-rater reliability was excellent, with an ICC single-measure coefficient of 0.944 (95%-confidence interval: [0.907; 0.966]). Gap sizes (mean ± SD / maximum) were 55 ± 9 / 143 µm at the margins, 68 ± 14 / 130 µm labially, and 78 ± 19 / 176 µm at the incisor edge for 3D-printed veneers. For milled veneers, gap sizes were 44 ± 11 / 141 µm at the margins, 85 ± 19 / 171 µm labially, and 391 ± 26 / 477 µm at the incisor edge. At the margins, the milled veneers outperformed the 3D-printed restorations (p = 0.011). The cement gap at the incisor edge was significantly smaller after 3D printing (p < 0.001). CONCLUSIONS: 3D-printed zirconia restorations showed clinically acceptable mean marginal gaps below 100 µm. Because drill compensation could be omitted with 3D printing, the fit at the sharp incisal edge was significantly tighter than with milling. CLINICAL SIGNIFICANCE: The fit of 3D-printed ceramic anterior restorations meets clinical standards. In addition, 3D printing is associated with a greater geometrical freedom than milling. With regard to fit this feature allows tighter adaptation even after minimally invasive preparation.

In vivo assessment of artefacts in MRI images caused by conventional twistflex and various fixed orthodontic CAD/CAM retainers.

PURPOSE: To assess magnetic resonance imaging (MRI) artefacts caused by different computer-aided design/computer-aided manufacturing (CAD/CAM) retainers in comparison with conventional hand bent stainless steel twistflex retainers in vivo. MATERIALS AND METHODS: MRI scans (3 Tesla) were performed on a male volunteer with different CAD/CAM retainers (cobalt-chromium, CoCr; nickel-titanium, NiTi; grade 5 titanium, Ti5) and twistflex retainers inserted. A total of 126 landmarks inside and outside the retainer area (RA; from canine to canine) were evaluated by two blinded radiologists using an established five-point visibility scoring (1: excellent, 2: good, 3: moderate, 4: poor, 5: not visible). Friedman and two-tailed Wilcoxon tests were used for statistical analysis (significance level: p < 0.05). RESULTS: Twistflex retainers had the strongest impact on the visibility of all landmarks inside (4.0 ± 1.5) and outside the RA (1.7 ± 1.2). In contrast, artefacts caused by CAD/CAM retainers were limited to the dental area inside the RA (CoCr: 2.2 ± 1.2) or did not impair MRI-based diagnostics in a clinically relevant way (NiTi: 1.0 ± 0.1; Ti5: 1.4 ± 0.6). CONCLUSION: The present study on a single test person demonstrates that conventional stainless steel twistflex retainers can severely impair the diagnostic value in head/neck and dental MRI. By contrast, CoCr CAD/CAM retainers can cause artefacts which only slightly impair dental MRI but not head/neck MRI, whereas NiTi and Ti5 CAD/CAM might be fully compatible with both head/neck and dental MRI.

Orthodontic shear bond strength and ultimate load tests of CAD/CAM produced artificial teeth.

OBJECTIVES: To investigate whether artificial CAD/CAM processed (computer-aided design/manufacturing) teeth could be a feasible option for the production of dental in vitro models for biomechanical testing. MATERIAL AND METHODS: Disks (n = 10 per group) made from two different CAD/CAM-materials, one fiber-reinforced composite (FRC; Trinia, Bicon) and one polymethylmethacrylate-based resin (PMMA; Telio CAD, Ivoclar Vivadent), as well as bovine teeth (n = 10), were tested for their shear bond strength (SBS) and scored according to the adhesive remnant index (ARI). In addition, CAD/CAM-manufactured lower incisor teeth were tested for their ultimate load (Fu). RESULTS: With regard to SBS, both PMMA (17.4 ± 2.2 MPa) and FRC (18.0 ± 2.4 MPa) disks showed no significant difference (p = 0.968) compared to bovine disks (18.0 ± 5.4 MPa). However, the samples differed with regard to their failure mode (PMMA: ARI 4, delamination failure; FRC: ARI 0 and bovine: ARI 1.6, both adhesive failure). With regard to Fu, FRC-based teeth could withstand significantly higher loads (708 ± 126 N) than PMMA-based teeth (345 ± 109 N) (p < 0.01). CONCLUSION: Unlike PMMA-based teeth, teeth made from FRC showed sufficiently high fracture resistance and comparable SBS. Thus, FRC teeth could be a promising alternative for the production of dental in vitro models for orthodontic testing. CLINICAL RELEVANCE: CAD/CAM-processed teeth made from FRC enable the use of standardized geometry and constant material properties. Using FRC teeth in dental in vitro studies has therefore the potential to identify differences between various treatment options with rather small sample sizes, while remaining close to the clinical situation.

DIPS (Dystonia Image-based Programming of Stimulation: a prospective, randomized, double-blind crossover trial).

INTRODUCTION: Deep brain stimulation of the internal globus pallidus is an effective treatment for dystonia. However, there is a large variability in clinical outcome with up to 25% non-responders even in highly selected primary dystonia patients. In a large cohort of patients we recently demonstrated that the variable clinical outcomes of pallidal DBS for dystonia may result to a large degree by the exact location and stimulation volume within the pallidal region. Here we test a novel approach of programing based on these insights: we first defined probabilistic maps of anti-dystonic effects by aggregating individual electrode locations and volumes of tissue activated of > 80 patients collected in a multicentre effort. We subsequently modified the algorithms to be able to test all possible stimulation settings of de novo patients in silico based on the expected clinical outcome and thus potentially predict the best possible stimulation parameters for the individual patients. METHODS: Within the framework of a BMBF-funded study, this concept of a computer-based prediction of optimal stimulation parameters for patients with dystonia will be tested in a randomized, controlled crossover study. The main parameter for clinical efficacy and primary endpoint is based on the blinded physician rating of dystonia severity reflected by Clinical Dystonia Rating Scales for both interventions (best clinical settings and model predicted settings) after 4 weeks of continuous stimulation. The primary endpoint is defined as "successful treatment with model predicted settings" (yes or no). The value is "yes" if the motor symptoms with model predicted settings are equal or better (tolerance 5% of absolute difference in percentages) to clinical settings. Secondary endpoints will include measures of quality of life, calculated energy consumption of the neurostimulation system and physician time for programming. PERSPECTIVE: We envision, that computer-guided deep brain stimulation programming in silico might provide optimal stimulation settings for patients with dystonia without the burden of months of programming sessions. The study protocol is designed to evaluate which programming method is more effective in controlling motor symptom severity and improving quality of life in dystonia (best clinical settings and model predicted settings). Trial registration Registered with ClinicalTrials.gov on Oct 27, 2021 (NCT05097001).

Influence of Preventive Tooth Extractions on Quality of Life in Patients with Antiresorptive Intake-A Prospective Longitudinal Study.

BACKGROUND: To find out whether preventive tooth extractions in patients on antiresorptive therapy have a direct impact on the patients' overall quality of life (QoL); Methods: QoL using the five-level version of the EuroQol Group's EQ-5D instrument (EQ-5D-5L) was longitudinally assessed in N = 114 prospectively enrolled patients with indication of preventive tooth extraction over a period of 12 months. Patients were stratified as high-risk (malignant disease with bone metastasis or multiple myeloma, with monthly high-dose antiresorptive therapy delivered intravenously [bisphosphonate] or subcutaneously [denosumab]) and low-risk/osteoporosis patients (weekly low-dose antiresorptive therapy administered orally [bisphosphonate] or half-yearly subcutaneously [denosumab]). The measurement time points were 4 weeks preoperatively (T0), 2 months (T1) and 1 year postoperatively (T2), respectively. RESULTS: EQ-5D-5L index scores fell in a range from -0.21 to 1.00 in the low-risk group to 0.15 to 1.00 in the high-risk group. The t-test comparing the baseline index scores of both groups showed EQ-5D-5L index score in the low-risk group (0.708 ± 0.292) to be significantly smaller (p = 0.037) than in the high-risk group (0.807 ± 0.19). ANCOVA showed no significant differences in EQ-5D-5L index scores between the groups at T1 and T2. CONCLUSIONS: Preventive tooth extractions in patients undergoing antiresorptive treatment have no negative effect on QoL. Therefore, if indicated, preventive tooth extraction should not be omitted. Patient-oriented outcome measures are important to obtain a good risk-benefit balance for patient-specific treatment.

Mechanical properties of CAD/CAM-fabricated in comparison to conventionally fabricated functional regulator 3 appliances.

Manufacturing of Fränkel's functional regulator 3 (FR3) is complicated and requires extensive knowledge from the dental technician. To determine whether FR3s produced by CAD/CAM techniques (CAD-FR3) meet similar mechanical properties like conventional FR3s (Con-FR3), for each of 10 patient cases, three CAD-FR3 designs (palatal connector cross-section 3 × 3 mm, 4 × 1 mm or 5 × 2 mm) and one Con-FR3 were subjected to cyclic loading and subsequent fracture testing in a universal testing device. Transversal load capacity (Fmax(FR3)) and stiffness were compared among the different CAD-FR3 designs and Con-FR3s using Friedman and Wilcoxon tests with a significance level of α = 0.05. All CAD-FR3 designs had significantly higher mean Fmax(FR3) (p ≤ 0.007) and stiffness (p ≤ 0.005) than the Con-FR3s. The CAD-FR33×3 had the highest mean Fmax(FR3) (98.2 ± 26.2 N) and stiffness (37.1 ± 15.5 N/mm), closely followed by the CAD-FR35×2 (Fmax(FR3): 90.3 ± 24.7 N; stiffness: 30.0 ± 12.3 N/mm). Among the CAD appliances, CAD-FR34×1 had the lowest values (p ≤ 0.007 for all pairwise tests) with Fmax(FR3) of 45.8 ± 17.9 N and stiffness of 12.5 ± 7.3 N/mm. CAD-FR3s have superior mechanical properties in comparison to Con-FR3s if certain design parameters are followed. Further clinical investigations have to examine if they can serve as an alternative in practice.

Expression of apoptosis repressor with caspase recruitment domain (ARC) in familial adenomatous polyposis (FAP) adenomas and its correlation with DNA mismatch repair proteins, p53, Bcl-2, COX-2 and beta-catenin.

BACKGROUND: Colorectal familial adenomatous polyposis (FAP) adenomas exhibit a uniform pathogenetic basis caused by a germline mutation in the adenomatous polyposis gene (APC), but the molecular changes leading to their development are incompletely understood. However, dysregulated apoptosis is known to substantially affect the development of colonic adenomas. One of the key regulatory proteins involved in apoptosis is apoptosis repressor with caspase recruitment domain (ARC). METHODS: The expression of nuclear and cytoplasmic ARC in 212 adenomas from 80 patients was analyzed by immunohistochemistry. We also compared expression levels of ARC with the expression levels of p53, Bcl-2, COX-2, and MMR proteins. Statistical analyses were performed by Spearman's rank correlation and linear regression test. RESULTS: ARC was overexpressed in the nuclei and cytoplasm of most FAP adenomas investigated. Cytoplasmic ARC staining was moderately stronger (score 2) in 49.1% (n = 104/212) and substantially stronger (score 3) in 32.5% (n = 69/212) of adenomas compared to non-tumorous colorectal mucosa. In 18.4% (n = 39/212) of adenomas, cytoplasmic ARC staining was equivalent to that in non-tumorous mucosa. Nuclear expression of ARC in over 75% of cells was present in 30.7% (n = 65/212) of investigated adenomas, and nuclear expression in 10-75% of cells was detected in 62.7% (n = 133/212). ARC expression in under 10% of nuclei was found in 6.6% (n = 14/212) of adenomas. The correlation between nuclear ARC expression and cytoplasmic ARC expression was highly significant (p = 0.001). Moreover, nuclear ARC expression correlated positively with overexpression of Bcl-2, COX-2 p53 and ß-catenin. Cytoplasmic ARC also correlated with overexpression of Bcl-2. Sporadic MMR deficiency was detected in very few FAP adenomas and showed no correlation with nuclear or cytoplasmic ARC. CONCLUSIONS: Our results demonstrated that both cytoplasmic and nuclear ARC are overexpressed in FAP adenomas, thus in a homogenous collective. The highly significant correlation between nuclear ARC and nuclear ß-catenin suggested that ARC might be regulated by ß-catenin in FAP adenomas. Because of its further correlations with p53, Bcl-2, and COX-2, nuclear ARC might play a substantial role not only in carcinomas but also in precursor lesions. Video Abstract.

Evaluation of magnetic resonance imaging artifacts caused by fixed orthodontic CAD/CAM retainers-an in vitro study.

OBJECTIVES: Magnetic resonance imaging (MRI) image quality can be severely impaired by artifacts caused by fixed orthodontic retainers. In clinical practice, there is a trend towards using computer-aided design/computer-aided manufacturing (CAD/CAM) retainers. This study aimed to quantify MRI artifacts produced by these novel CAD/CAM retainers. MATERIAL AND METHODS: Three CAD/CAM retainers and a stainless-steel retainer ("Twistflex"; clinical reference standard) were scanned in vitro at 3-T MRI using a high-resolution 3D sequence. The artifact diameters and three-dimensional artifact volumes (AV) were determined for all mandibular (AVmand) and maxillary (AVmax) retainers. Moreover, the corresponding ratio of artifact volume to retainer volume (AV/RVmand, AV/RVmax) was calculated. RESULTS: Twistflex caused large artifact volumes (AVmand: 13530 mm3; AVmax: 15642 mm3; AV/RVmand: 2602; AV/RVmax: 2235). By contrast, artifact volumes for CAD/CAM retainers were substantially smaller: whereas artifact volumes for cobalt-chromium retainers were moderate (381 mm3; 394 mm3; 39; 31), grade-5 titanium (110 mm3; 126 mm3; 12; 12) and nickel-titanium (54 mm3; 78 mm3; 12; 14) both produced very small artifact volumes. CONCLUSION: All CAD/CAM retainers caused substantially smaller volumes of MRI artifacts compared to Twistflex. Grade-5 titanium and nickel-titanium CAD/CAM retainers showed the smallest artifact volumes. CLINICAL RELEVANCE: CAD/CAM retainers made from titanium or nickel-titanium may not relevantly impair image quality in head/neck and dental MRI. Artifacts caused by cobalt-chromium CAD/CAM retainers may mask nearby dental/periodontal structures. In contrast, the large artifacts caused by Twistflex are likely to severely impair diagnosis of oral and adjacent pathologies.

Accuracy of laser-melted patient-specific implants in genioplasty - A three-dimensional retrospective study.

PURPOSE: To assess the accuracy of laser-melted patient-specific implants (PSI) with regard to a preoperative virtual treatment plan for genioplasty based on a new analysis method without the use of landmarks. MATERIALS AND METHODS: A retrospective evaluation of a cohort of Class II and Class III patients who had undergone virtually planned orthognathic surgery (including genioplasty) was carried out. The preoperative virtual treatment plan and the postoperative outcome were fused to calculate the translational and rotational discrepancies between the 3D planning and the actual surgical outcome. RESULTS: The accuracy of left/right positioning was 0.25 ± 0.28 mm (p < 0.001), that of anterior/posterior positioning was 0.70 ± 0.64 mm (p < 0.001), and that of up/down-positioning was 0.45 ± 0.38 mm (p < 0.001). The rotational discrepancies were less than 2 deg. The virtually planned and postoperative positions of the chin differed significantly from each other (p < 0.001 for all rotational and translational discrepanices). CONCLUSION: The findings demonstrate that PSIs can transfer the planned virtual genioplasty into the operation theatre with small but significant deviations. However, since no conclusions can be drawn from the results regarding surgical success in terms of shaping the soft tissue profile as well as the esthetic result, no superiority of PSI over traditional plate osteosynthesis can be demonstrated.

KCNJ6 variants modulate reward-related brain processes and impact executive functions in attention-deficit/hyperactivity disorder.

KCNJ6, encoding a potassium channel subunit, regulates the excitability of dopaminergic neurons and is expressed in attention-deficit/hyperactivity disorder (ADHD)-relevant brain regions. As a potential ADHD risk gene, KCNJ6, therefore, may contribute to the endophenotypic variation of the disorder. The impact of two SNPs, rs7275707 and rs6517442, both located in the transcriptional control region of KCNJ6, on reporter gene expression was explored in cultured cells. The KCNJ6 variants were then tested for association with ADHD and personality traits in a family-based sample (165 affected children) and an adult case-control sample (450 patients, 426 controls). Furthermore, the genotypic influence on performance in an n-back task and a cued continuous performance test (cCPT) was investigated by electroencephalography recordings. Finally, rs6517442 function was assessed by a reward anticipation paradigm using functional magnetic resonance imaging. Different haplotypes of rs7275707 and rs6517442 significantly influenced KCNJ6 gene expression proving their functional relevance on the molecular level. In the family-based children sample rs7275707 was associated with ADHD (p = .038). Moreover, rs7275707 showed association with the personality trait of Reward Dependence (p = .031). In the ADHD group, both rs7275707 and rs6517442 influenced the Go-centroid location in the cCPT and the N200 amplitude in the n-back task. Furthermore, ventral striatal activation was impacted by rs6517442 during reward anticipation. Our data indicate that functional variants of KCNJ6 influence brain activity during reward-related and executive processes supporting the view of a differential, age-dependent modulatory impact of dopamine-related brain processes in ADHD risk.

Rationale and design of the Mineralocorticoid Receptor Antagonists in End-Stage Renal Disease Study (MiREnDa).

BACKGROUND: End-stage renal disease (ESRD) patients exhibit an extraordinarily high annual mortality secondary to cardiac and vascular causes, particularly sudden cardiac death (SCD). Left ventricular (LV) hypertrophy is a frequent finding and constitutes an independent predictor of mortality risk in these patients. Mineralocorticoid receptor antagonists (MRAs) are cardioprotective in heart failure patients and effectively reduce LV mass, but are considered inappropriate in patients with severe renal impairment, given their potential to cause hyperkalaemia. Recent data from small clinical studies suggest that MRAs may be safe in patients undergoing regular haemodialysis, but cardiovascular (CV) protection in these patients is unclear. We here review the literature on CV effects of MRA in dialysis patients and report the design of the Mineralocorticoid Receptor antagonists in End-stage renal Disease (MiREnDa) trial. METHODS: The MiREnDa trial is a prospective randomized, placebo-controlled, double-blind, parallel group, multi-centre, intervention study investigating the effects of spironolactone (50 mg daily) compared with placebo in maintenance haemodialysis patients. The change in LV mass index (LVMI) as assessed by cardiac magnet resonance imaging (CMR) constitutes the primary efficacy end point. Secondary end points include changes in LV geometry and function, office and 24-h ambulatory blood pressure, cardiac arrhythmias, vascular function parameters, measures of heart failure and quality of life. Pre-dialysis potassium levels and the incidence of threatening hyperkalaemia (pre-dialysis potassium ≥6.5 mmol/L) constitute safety end points. CONCLUSIONS: MiREnDa will investigate CV efficacy and safety of spironolactone in haemodialysis patients [clinical trials.gov NCT01691053].

Influence of a genetic variant of the neuronal growth associated protein Stathmin 1 on cognitive and affective control processes: an event-related potential study.

Stathmin 1 (STMN1) is a neuronal growth associated protein (NGAP) that is involved in microtubule dynamics and plays an important role in neurite outgrowth and synaptic plasticity. It is highly expressed in the amygdala, but also in different areas of the neocortex including the frontal lobe. Based on previous findings regarding an impact of STMN1 on fear processing, the present study aimed at extending the evidence concerning its functional role to include the domain of executive (frontal lobe) functions. To this end, a group of 59 healthy volunteers stratified for the single-nucleotide polymorphism rs182455 of the STMN1 gene was examined by means of three experimental paradigms probing different aspects of cognitive-affective functioning. Event-related potential measures of cognitive response control, emotional interference processing, and action monitoring were analyzed. STMN1 genotype significantly affected the NoGo-anteriorization (NGA)-a neurophysiological marker of cognitive response control associated with medial prefrontal cortex activation-as well as the modulation of the P300 by the valence of emotional Stroop stimuli. In both cases, carriers of the rs182455 C-allele showed altered cognitive-affective processing; effects appeared to be more pronounced in females. Our findings indicate a functional impact of STMN1 on cognitive and affective control processes, thereby complementing previous evidence on its role in fear processing. Based on these results, an influence of STMN1 should be considered in studies aiming at the etiopathogenesis of a broad range of neuropsychiatric disorders with dysfunctional networking, including neurodegenerative disorders as well as schizophrenia, autism spectrum disorders, anxiety disorders, depression, and ADHD.