Longitudinal analysis of microcirculatory parameters in gingival tissues after tooth extraction in patients with different risk profiles for wound healing disorders - a pilot study.

OBJECTIVES: We aimed to establish a risk profile for intraoral wound healing disorders based on measurements of microcirculation in gingival tissues. MATERIALS AND METHODS: Oxygen saturation (SO2) and blood flow in gingival tissues were measured with tissue spectrometry and laser doppler spectroscopy in 37 patients before/after tooth extractions. Patients were assigned to four groups: anamnestically and periodontally healthy patients (n = 7), anamnestically healthy but suffering from periodontitis (n = 10), anamnestically healthy but smoking and suffering from periodontitis (n = 10) and suffering from diabetes and periodontitis (n = 10). Measurements were performed at three different time points: Baseline measurement (T0), one day post extractionem (p.e.) (T1) and seven days p.e. (T2). RESULTS: Baseline SO2 values were higher in control patients (p = .038). This effect was most evident in comparison to smokers suffering from periodontitis (p = .042), followed by diabetics suffering from periodontitis (p = .09). An opposite trend was seen for blood flow. Patients suffering from periodontitis demonstrated higher blood flow values (p = .012). Five patients, which belonged to the group of smokers suffering from periodontitis, showed clinically a delayed wound healing. CONCLUSION: Differences in SO2 and blood flow of gingival tissue could be detected in different groups of patients with existing periodontitis compared to control patients. CLINICAL RELEVANCE: Lower baseline SO2 values could be a warning signal for possible wound healing disorders after oral surgery.

Modification of the van der Waals and Platteeuw model for gas hydrates considering multiple cage occupancy.

This study reviews available van der Waals- and Platteeuw-based hydrate models considering multiple occupancy of cavities. Small guest molecules, such as hydrogen and nitrogen, are known to occupy lattice cavities multiple times. This phenomenon has a significant impact on hydrate stability and thermodynamic properties of the hydrate phase. The objective of this work is to provide a comprehensive overview and required correlations for the implementation of a computationally sufficient cluster model that considers up to five guest molecules per cavity. Two methodologies for cluster size estimation are evaluated by existing nitrogen hydrate models showing accurate results for phase equilibria calculations. Furthermore, a preliminary hydrogen hydrate model is introduced and compared with the results of other theoretical studies, indicating that double occupancy of small sII cavities is improbable and four-molecule clusters are predominant in large sII cavities for pressures above 300 MPa. This work lays the foundation for further exploration and optimization of hydrate-based technologies for small guest molecules, e.g., storage and transportation, emphasizing their role in the future landscape of sustainable energy solutions.

The Small RNA-Binding Protein CcaF1 Promotes Formation of Photosynthetic Complexes in Rhodobacter sphaeroides.

In natural habitats, bacteria frequently need to adapt to changing environmental conditions. Regulation of transcription plays an important role in this process. However, riboregulation also contributes substantially to adaptation. Riboregulation often acts at the level of mRNA stability, which is determined by sRNAs, RNases, and RNA-binding proteins. We previously identified the small RNA-binding protein CcaF1, which is involved in sRNA maturation and RNA turnover in Rhodobacter sphaeroides. Rhodobacter is a facultative phototroph that can perform aerobic and anaerobic respiration, fermentation, and anoxygenic photosynthesis. Oxygen concentration and light conditions decide the pathway for ATP production. Here, we show that CcaF1 promotes the formation of photosynthetic complexes by increasing levels of mRNAs for pigment synthesis and for some pigment-binding proteins. Levels of mRNAs for transcriptional regulators of photosynthesis genes are not affected by CcaF1. RIP-Seq analysis compares the binding of CcaF1 to RNAs during microaerobic and photosynthetic growth. The stability of the pufBA mRNA for proteins of the light-harvesting I complex is increased by CcaF1 during phototrophic growth but decreased during microaerobic growth. This research underlines the importance of RNA-binding proteins in adaptation to different environments and demonstrates that an RNA-binding protein can differentially affect its binding partners in dependence upon growth conditions.

Synergy of Regenerative Periodontal Surgery and Orthodontics Improves Quality of Life of Patients with Stage IV Periodontitis: 24-Month Outcomes of a Multicenter RCT.

In stage IV periodontitis patients with pathologic tooth migration (PTM), interdisciplinary treatment includes regenerative periodontal surgery (RPS) with an application of biomaterials and orthodontic therapy (OT) to restore function, esthetics and thereby quality of life (QoL). In a 24-month randomized trial we explored the synergy between regenerative medicine and biomechanical force application. The following methods were used: Forty-three patients had been randomized to a combined treatment comprising RPS and subsequent OT starting either 4 weeks (early OT) or 6 months (late OT) post-operatively. Clinical periodontal parameters and oral health-related QoL (GOHAI) were recorded up to 24 months. We obtained the following results: Mean clinical attachment gain (∆CAL ± SD) was significantly higher with early OT (5.96 ± 2.1 mm) versus late OT (4.65 ± 1.76 mm) (p = 0.034). Pocket closure (PPD ≤ 4 mm) was obtained in 91% of defects with early OT compared to 90% with late OT. GOHAI-scores decreased significantly from 26.1 ± 7.5 to 9.6 ± 4.7 (early OT) and 25.1 ± 7.1 to 12.7 ± 5.6 (late OT). Inconclusion, teeth severely compromised by intrabony defects and PTM can be treated successfully by RPS followed by early OT with the advantage of an overall reduced treatment time. As a result of the combined periodontal-orthodontic therapy, the oral health-related QoL of patients was significantly improved. Early stimulation of wound healing with orthodontic forces had a favorable impact on the outcomes of regenerative periodontal surgery.

Clinical implementation of axial angulation of incisors in the course of routine fixed appliance treatment - a retrospective cohort study.

PURPOSE: To identify clinically relevant factors for changes in axial angulation of incisors during routine fixed appliance orthodontic treatment. METHODS: A total of 106 patients (grades 1-2 of IOTN, 64 females, 42 males; mean age: 15.5 years) from a private practice and treated with metal or ceramic brackets were included in this retrospective cohort study. The axial angulation of the upper and lower incisors was measured on lateral cephalograms before insertion of the first rectangular 0.016 × 0.022-in NiTi archwire (T0) and at the end of treatment about 8 weeks after insertion of the working 0.019 × 0.025-in stainless steel archwire (T1). Treatment-related changes according to bracket type, initial situation, premolar extraction, angle class, and skeletal vertical configuration were analyzed. RESULTS: Although statistically significant treatment-related changes were seen for both the upper incisors (+ 1.3°) and the lower incisors (- 5.2°), only in ten patients (9.4%) was the prescribed torque value of 17° for the upper incisors and in no patient for the lower incisors achieved. A negative association between the induced change of axial angulation of incisors and the initial values was detected for the upper incisors as well as for the lower incisors. A comparison of the angle classes revealed significant differences in incisor changes. At the end of therapy, only a slight change for the upper central incisors in patients in angle class I cases and a significantly greater change in patients with angle class II/2 was observed. Cases with premolar extraction ended with lower axial angulation of the incisor than cases without extraction. The individual analysis of possible influencing factors also revealed an association with the vertical skeletal configuration. CONCLUSIONS: For the first time, the presented data show clinically relevant influencing factors for incisor axial angulation changes of the upper and lower incisors in relation to the torque value of the applied brackets in the course of routine clinical practice. For the orthodontist, it remains mandatory to decide whether a customized system must be individualized in order to achieve individual therapy goals.

A Small RNA, UdsC, Interacts with the RpoHII mRNA and Affects the Motility and Stress Resistance of Rhodobacter sphaeroides.

sRNAs have an important role in the regulation of bacterial gene expression. The sRNA, UdsC, of Rhodobacter sphaeroides is derived from the 3' UTR of the RSP_7527 mRNA, which encodes a hypothetical protein. Here, we showed the effect of UdsC on the resistance of Rhodobacter sphaeroides to hydrogen peroxide and on its motility. In vitro binding assays supported the direct interaction of UdsC with the 5' UTR of the rpoHII mRNA. RpoHII is an alternative sigma factor with an important role in stress responses in R. sphaeroides, including its response to hydrogen peroxide. We also demonstrated that RpoHII controls the expression of the torF gene, which encodes an important regulator of motility genes. This strongly suggested that the observed effect of UdsC on TorF expression is indirect and mediated by RpoHII.

Post-treatment Stability in Orthodontic Retention with Twistflex Retainers-Do Patients Benefit from Additional Removable Retainers?

OBJECTIVES: To evaluate post-treatment movements of lower anterior teeth during orthodontic retention in patients with fixed twistflex retainers versus those with combined fixed and removable retainers. MATERIALS AND METHODS: This study was based on a retrospective data analysis of 57 adult patients during orthodontic retention. They were assigned to two groups: In group 1 (n = 30) the lower jaw was provided with twistflex retainers only and in group 2 (n = 27) with a twistflex combined with a removable retainer for night-time use. Orthodontic study models of the lower jaw were digitalized and superimposed. Tooth movements were analyzed at the retainer bonding (t0) and follow-up appointment ≥ six months later (t1). Rotational tooth movements (°) were measured around the x-axis (mesial/distal direction), the y-axis (buccal/lingual direction) and the z-axis (longitudinal direction, tooth axis). Translational tooth movements (mm) were registered along the x-axis (buccal/lingual direction), the y-axis (mesial/distal direction) and the z-axis (apical/coronal direction). RESULTS: Canine and incisor position changes during orthodontic retention were more pronounced in group 1 compared to group 2 except for canine rotations around the z-axis. In both groups in most of the cases stable lower incisor alignment could be found, but the proportion was significant higher in group 2 (group 1: 56.7% vs. group 2: 81.5%). Severe misalignment was present in 13.3% of the participants of group 1 and only in 7.4% of group 2. The extent of canine tipping and movements along the x- and y-axis in severe misalignment cases was significantly lower in group 2 compared to 1. CONCLUSIONS: Lower incisor alignment was more stable in patients with combined fixed and removable retainers compared to fixed retainers only. CLINICAL RELEVANCE: Based on the present findings, the routinely application of supplementary removable retainers can be recommended to enhance anterior tooth alignment in patients with fixed twistflex retainers.

Interaction of periodontitis and orthodontic tooth movement-an in vitro and in vivo study.

OBJECTIVES: The aim of this in vitro and in vivo study was to investigate the interaction of periodontitis and orthodontic tooth movement on interleukin (IL)-6 and C-X-C motif chemokine 2 (CXCL2). MATERIALS AND METHODS: The effect of periodontitis and/or orthodontic tooth movement (OTM) on alveolar bone and gingival IL-6 and CXCL2 expressions was studied in rats by histology and RT-PCR, respectively. The animals were assigned to four groups (control, periodontitis, OTM, and combination of periodontitis and OTM). The IL-6 and CXCL2 levels were also studied in human gingival biopsies from periodontally healthy and periodontitis subjects by RT-PCR and immunohistochemistry. Additionally, the synthesis of IL-6 and CXCL2 in response to the periodontopathogen Fusobacterium nucleatum and/or mechanical strain was studied in periodontal fibroblasts by RT-PCR and ELISA. RESULTS: Periodontitis caused an increase in gingival levels of IL-6 and CXCL2 in the animal model. Moreover, orthodontic tooth movement further enhanced the bacteria-induced periodontal destruction and gingival IL-6 gene expression. Elevated IL-6 and CXCL2 gingival levels were also found in human periodontitis. Furthermore, mechanical strain increased the stimulatory effect of F. nucleatum on IL-6 protein in vitro. CONCLUSIONS: Our study suggests that orthodontic tooth movement can enhance bacteria-induced periodontal inflammation and thus destruction and that IL-6 may play a pivotal role in this process. CLINICAL RELEVANCE: Orthodontic tooth movement should only be performed after periodontal therapy. In case of periodontitis relapse, orthodontic therapy should be suspended until the periodontal inflammation has been successfully treated and thus the periodontal disease is controlled again.

Numerical and biomechanical analysis of orthodontic treatment of recovered periodontally compromised patients.

OBJECTIVE: Generate a finite element (FE) model to simulate space closure and retraction mechanics for anterior maxillary teeth in periodontally compromised dentition, and compare the biomechanical effect of initial force systems with varying magnitude. MATERIALS AND METHODS: The geometry of an idealized finite element model (FEM) of a maxilla was adapted such that the teeth showed reduced periodontal support together with extruded and flared incisors. In a first step, leveling and alignment of the front teeth were simulated. In a second step, force systems for orthodontic space closure of residual spaces on both sides distal to the lateral incisors were simulated. A combined intrusion and retraction cantilever was modeled, to simulate en masse retraction mechanics with segmented arches and elastic chains. A commercial FE system was used for all model generations and simulations. RESULTS: Results of the simulations indicated that a force of 1.0 N is too high for space closure of flared front teeth in periodontally damaged dentition, as extreme strains may occur. En masse retraction using cantilever mechanics with lower forces showed a uniform intrusion and retraction movement and thus proved to be a better option for treating patients with a periodontally compromised dentition. CONCLUSION: The outcome of this study indicates that increased periodontal stresses resulting from severe attachment loss should be seriously considered by careful planning of the orthodontic mechanics and reduction of the applied forces is suggested. The presented cantilever mechanics seems to be an appropriate means for en masse retraction of periodontally compromised extruded front teeth.

Comparison of multiforce nickel-titanium wires to multistrand wires without force zones in bending and torque measurements.

PURPOSE: The aim was to compare rectangular multiforce nickel-titanium (NiTi) wires to rectangular wires with only one force zone. Both types of wires are primarily intended for use during the levelling phase of orthodontic treatment. Thus, basic mechanical properties were examined by means of a three-point bending test. Torque expression, which is dependent on both wire parameters and interslot distances, was analyzed using the Orthodontic Measurement and Simulation System (OMSS). MATERIAL/METHODS: Four multizone products were tested: DuoForce™ (Forestadent, Pforzheim, Germany), TriTanium™ (American Orthodontics, Sheboygan, WI, USA), Triple Force™ (ODS, Kisdorf, Germany), Bio-Active™ (GC, Breckerfeld, Germany), and two multistrand products without force zones: a nine-strand NiTi, TurboWire™ (Ormco, Orange, CA, USA) and an eight-strand stainless steel (SS) wire, Multibraid™ (GAC, Dentsply Sirona, York, PA, USA). All the wires had the dimension 0.40 mmâ€¯× 0.56 mm (0.016 inchâ€¯× 0.022 inch) except the nine-strand NiTi wire TurboWire™, which had a dimension of 0.43 mmâ€¯× 0.65 mm (0.017 inchâ€¯× 0.025 inch). Six different bracket systems in the 0.018 inch slot system were chosen: the conventional brackets discovery® and discovery® smart (Dentaurum, Ispringen, Germany), the active self-ligating brackets InOvation™ and InOvation™ mini (GAC, Dentsply Sirona, York, PA, USA) and the passive self-ligating brackets Carrière™ (ODS, Kisdorf, Germany) and BioPassive® (Forestadent, Pforzheim, Germany). The first set-up was a three-point bending test according to DIN EN ISO 15841. For the second experiment, the bracket products glued on a maxilla model were combined with the wire products. The torque moments arising during torqueing of the wires between +20° and -20° were measured in three positions: first incisor, canine and second bicuspid. RESULTS: Bending tests confirmed variation of the force corresponding to the force zones. The nine-strand NiTi wire TurboWireTM and the eight-strand SS wire Multibraid™ did not show any variation dependent on the tested area. Torque-moments generated by the multizone wires were higher compared to the braided wires. The nine-strand NiTi wire showed the lowest moments in spite of the higher dimension. As expected, increasing the interbracket distance reduced the torque moments. CONCLUSION: The tests verified the existence of multiple force zones in the NiTi wires for forces and moments, respectively. As the torque-moments arising from the multizone wires were rather high, it is not recommended to use these wires as a first "leveling wire" in orthodontic treatment, especially in extremely crowded cases.

Role of chaperone-assisted selective autophagy (CASA) in mechanical stress protection of periodontal ligament cells.

OBJECTIVE: The periodontal ligament (PDL) is exposed to constant mechanical forces potentiated by orthodontic tooth movement (OTM). The aim of our study was to investigate the involvement of chaperone-assisted selective autophagy (CASA) in mechanosensing and cellular adaption to forces in the PDL. MATERIALS AND METHODS: Human PDL cells were loaded with 2.5, 5, and 10% of static mechanical strain for 24 h in vitro. Untreated cells served as controls. Gene expression of HSPA8, HSPB8, BAG3, STUB1, SYNPO2 was investigated via RT-qPCR (Quantitative reverse transcription PCR). Western blot evidenced protein expression of these molecules and of Filamin A. In vivo analyses of CASA were performed via immunohistochemistry on teeth with and without OTM. RESULTS: CASA machinery genes were inherently expressed in PDL cells and exhibited transcriptional induction upon mechanical strain. Protein analyses underlined these findings, even though modulation upon force exertion also demonstrated a decrease for some molecules and loading strengths. In vivo results evidenced again the uniform upregulation of HSPA8, HSPB8, BAG3, STUB1, SYNPO2 and Filamin A in teeth with OTM compared to controls. Experiments generally evidenced a pronounced variability in the expression between donors both on the gene and protein level. CONCLUSIONS: Our study is the first to identify both the expression and functional relevance of CASA in the PDL. The data reflect its probable central role in adequate adaption to forces exerted by OTM and in mechanical stress protection of cells. Deeper knowledge of the CASA pathway will allow better assessment of predisposing factors regarding side effects during mechanical force application that can be used in orthodontic practice.

Autophagy Induces Expression of IL-6 in Human Periodontal Ligament Fibroblasts Under Mechanical Load and Overload and Effects Osteoclastogenesis in vitro.

Objective: Autophagy is an important cellular adaptation mechanism to mechanical stress. In animal experiments, inhibition of autophagy during orthodontic tooth movement triggered increased expression of inflammation-related genes and decreased bone density. The aim of this study was to investigate how autophagy affects cytokine levels of interleukin 6 (IL-6) in human periodontal ligament (hPDL) fibroblasts under mechanical pressure and the resulting influence on osteoblast communication. Methods: hPDL fibroblasts were subjected to physiologic mechanical load, constant overload, or rapamycin treatment for 16 to 24 h ± autophagy inhibitor 3-MA. Autophagosomes were quantified by flow cytometry. Gene expression of il-6 as well as IL-6 levels in the supernatant were determined with rtPCR and ELISA. To investigate the influence of mechanically-induced autophagy on cell-cell communication, an osteoblast-culture was subjected to supernatant from stimulated hPDL fibroblasts ± soluble IL-6 receptor (sIL-6R). After 24 h, osteoprotegerin (opg) and receptor activator of nuclear factor κB ligand (rankl) gene expressions were detected with rtPCR. Gene expression of a disintegrin and metalloproteinases (adam) 10 and 17 in stimulated hPDL fibroblasts was examined via rtPCR. Results: Autophagy was induced by biomechanical stress in hPDL fibroblasts in a dose-dependent manner. Mechanical load and overload increased IL-6 expression at gene and protein level. Autophagy inhibition further enhanced the effects of mechanical stimulation on IL-6 expression. Mechanical stimulation of hPDL fibroblasts downregulated adam10 and adam17 expressions. Inhibition of autophagy had stimulus-intensity depending effects: autophagy inhibition alone or additional application of physiological stress enhanced adam10 and adam17 expressions, whereas mechanical overload had adverse effects. Osteoblasts showed significantly reduced opg expression in the presence of supernatant derived of hPDL fibroblasts treated with autophagy inhibitor and sIL-6R. Conclusion: IL-6 levels were increased in response to pressure in hPDL fibroblasts, which was further enhanced by autophagy inhibition. This caused a decrease in opg expression in osteoblasts. This may serve as an explanatory model for accelerated tooth movement observed under autophagy inhibition, but may also represent a risk factor for uncontrolled bone loss.

Dose rate correction for a silicon diode detector array.

PURPOSE: A signal dependence on dose rate was reported for the ArcCHECK array due to recombination processes within the diodes. The purpose of our work was to quantify the necessary correction and apply them to quality assurance measurements. METHODS: Static 10 × 10 cm2 6-MV fields delivered by a linear accelerator were applied to the detector array while decreasing the average dose rate, that is, the pulse frequency, from 500 to 30 MU/min. An ion chamber was placed inside the ArcCHECK cavity as a reference. Furthermore, the instantaneous dose rate dependence (DRD) was studied. The position of the detector was adjusted to change the dose-per-pulse, varying the distance between the focus and the diode closest to the focus between 69.6 and 359.6 cm. Reference measurements were performed with an ion chamber placed inside a PMMA slab phantom at the same source-to-detector distances ( S D D s ) . Exponential saturation functions were fitted to the data, with different parameters to account for two generations of ArcCHECK detectors (types 2 and 3) and both DRDs. Corrections were applied to 12 volumetric modulated arc therapy plans. RESULTS: The sensitivity decreased by up to 2.8% with a decrease in average dose rate and by 9% with a decrease in instantaneous dose rate. Correcting the average DRD, the mean gamma pass rates (2%/2-mm criterion) of the treatment plans were improved by 5 percentage points (PP) for diode type 3 and 0.4 PP for type 2. Correcting the instantaneous DRD, the improvement was 8.4 PP for type 3 and 0.9 PP for type 2. CONCLUSIONS: The instantaneous DRD was identified as the prevailing effect on the diode sensitivity. We developed and validated a method to correct this behavior. The number of falsely not passed treatment plans could be considerably reduced.

Cortical representation of experimental periodontal pain: a functional magnetic resonance imaging study.

The aim of this study was to investigate central pain representations during loading of the periodontium induced by orthodontic and occlusal stress. Nineteen healthy male volunteers (25.7 ± 2.8 years) were tested on two consecutive days: after phenotyping (questionnaires) and determination of warmth (WPT) and heat (HPT) pain thresholds, functional magnetic resonance imaging was performed as event-related paradigm including 36 tooth clenchings of 3 s duration, alternating with rest periods varying between 20-30 s. The task was performed in absence (T1) and 24 h after placement of an elastic separator between the second bicuspid and the first molar on the right side of the lower jaw (T2). No significant changes in WPT and HPT were observed but pain ratings were significantly elevated at T2. Significantly elevated activation at T2, as compared to T1, was found in bilateral sensorimotor cortex, bilateral secondary sensory cortex, supplementary motor area, right rolandic operculum, and bilateral insula. Our data show for the first time in humans that periodontal stimulation, as tested by tooth clenching in the presence of an elastic separator, goes along with specific expressions of pain at behavioral and neuronal network levels. Findings supplement the existing neuroimaging literature on odontogenic pain.

A Complex Network of Sigma Factors and sRNA StsR Regulates Stress Responses in R. sphaeroides.

Adaptation of bacteria to a changing environment is often accompanied by remodeling of the transcriptome. In the facultative phototroph Rhodobacter sphaeroides the alternative sigma factors RpoE, RpoHI and RpoHII play an important role in a variety of stress responses, including heat, oxidative stress and nutrient limitation. Photooxidative stress caused by the simultaneous presence of chlorophylls, light and oxygen is a special challenge for phototrophic organisms. Like alternative sigma factors, several non-coding sRNAs have important roles in the defense against photooxidative stress. RNAseq-based transcriptome data pointed to an influence of the stationary phase-induced StsR sRNA on levels of mRNAs and sRNAs with a role in the photooxidative stress response. Furthermore, StsR also affects expression of photosynthesis genes and of genes for regulators of photosynthesis genes. In vivo and in vitro interaction studies revealed that StsR, that is under control of the RpoHI and RpoHII sigma factors, targets rpoE mRNA and affects its abundance by altering its stability. RpoE regulates expression of the rpoHII gene and, consequently, expression of stsR. These data provide new insights into a complex regulatory network of protein regulators and sRNAs involved in defense against photooxidative stress and the regulation of photosynthesis genes.

The effect of timing of orthodontic therapy on the outcomes of regenerative periodontal surgery in patients with stage IV periodontitis: A multicenter randomized trial.

AIM: To compare the outcomes after early (4 weeks post surgery) or late (6 months post surgery) orthodontic therapy (OT) following regenerative surgery of intra-bony defects (IDs). MATERIALS AND METHODS: In a multi-center, parallel-group, randomized clinical trial, 43 patients with stage IV periodontitis were randomized to receive either early (n = 23) or late OT (n = 20) following regenerative surgery of IDs. Primary outcome was change in clinical attachment level (CAL) in one target ID at 12 months after surgery. Secondary outcomes were changes of probing pocket depth (PPD), bleeding on probing (BOP), and frequency of pocket closure. RESULTS: No statistically significant differences between groups could be observed for CAL gain (5.4 mm [±2.1 mm] for early; 4.5 mm [±1.7 mm] for late OT). PPD was reduced by 4.2 mm (±1.9 mm) in the early group and by 3.9 mm (±1.5 mm) in the late group (p > .05). Pocket closure (PPD ≤ 4 mm) was obtained in 91% of defects in early compared to 85% in late OT. CONCLUSION: In the inter-disciplinary treatment of periodontitis stage IV, OT can be initiated already 4 weeks after regenerative surgery of IDs with favourable results, thus reducing the overall treatment time.

Extending the allelic spectrum at noncoding risk loci of orofacial clefting.

Genome-wide association studies (GWAS) have generated unprecedented insights into the genetic etiology of orofacial clefting (OFC). The moderate effect sizes of associated noncoding risk variants and limited access to disease-relevant tissue represent considerable challenges for biological interpretation of genetic findings. As rare variants with stronger effect sizes are likely to also contribute to OFC, an alternative approach to delineate pathogenic mechanisms is to identify private mutations and/or an increased burden of rare variants in associated regions. This report describes a framework for targeted resequencing at selected noncoding risk loci contributing to nonsyndromic cleft lip with/without cleft palate (nsCL/P), the most frequent OFC subtype. Based on GWAS data, we selected three risk loci and identified candidate regulatory regions (CRRs) through the integration of credible SNP information, epigenetic data from relevant cells/tissues, and conservation scores. The CRRs (total 57 kb) were resequenced in a multiethnic study population (1061 patients; 1591 controls), using single-molecule molecular inversion probe technology. Combining evidence from in silico variant annotation, pedigree- and burden analyses, we identified 16 likely deleterious rare variants that represent new candidates for functional studies in nsCL/P. Our framework is scalable and represents a promising approach to the investigation of additional congenital malformations with multifactorial etiology.

Regulation of Anti-Apoptotic SOD2 and BIRC3 in Periodontal Cells and Tissues.

The aim of the study was to clarify whether orthodontic forces and periodontitis interact with respect to the anti-apoptotic molecules superoxide dismutase 2 (SOD2) and baculoviral IAP repeat-containing protein 3 (BIRC3). SOD2, BIRC3, and the apoptotic markers caspases 3 (CASP3) and 9 (CASP9) were analyzed in gingiva from periodontally healthy and periodontitis subjects by real-time PCR and immunohistochemistry. SOD2 and BIRC3 were also studied in gingiva from rats with experimental periodontitis and/or orthodontic tooth movement. Additionally, SOD2 and BIRC3 levels were examined in human periodontal fibroblasts incubated with Fusobacterium nucleatum and/or subjected to mechanical forces. Gingiva from periodontitis patients showed significantly higher SOD2, BIRC3, CASP3, and CASP9 levels than periodontally healthy gingiva. SOD2 and BIRC3 expressions were also significantly increased in the gingiva from rats with experimental periodontitis, but the upregulation of both molecules was significantly diminished in the concomitant presence of orthodontic tooth movement. In vitro, SOD2 and BIRC3 levels were significantly increased by F. nucleatum, but this stimulatory effect was also significantly inhibited by mechanical forces. Our study suggests that SOD2 and BIRC3 are produced in periodontal infection as a protective mechanism against exaggerated apoptosis. In the concomitant presence of orthodontic forces, this protective anti-apoptotic mechanism may get lost.

Interplay between formation of photosynthetic complexes and expression of genes for iron-sulfur cluster assembly in Rhodobacter sphaeroides?

Formation of photosynthetic complexes leads to a higher demand for Fe-S clusters. We hypothesized that in the facultative phototrophic alpha-proteobacterium Rhodobacter sphaeroides expression of the isc-suf operon for Fe-S cluster formation may be increased under conditions that promote formation of photosynthetic complexes and that, vice versa, lack of the IscR regulator may also affect photosynthesis gene expression. To test this hypothesis, we monitored the activities of the isc-suf sense and anti-sense promoters under different growth conditions and in mutants which are impaired in formation of photosynthetic complexes. We also tested expression of photosynthesis genes in a mutant lacking the IscR regulator. Our results are not in agreement with a co-regulation of the Isc-Suf system and the photosynthetic apparatus at level of transcription. We provide evidence that, coordination of the systems occurs at post-transcriptional levels. Increased levels of isc-suf mRNAs under conditions promoting formation of photosynthetic complexes are due to higher RNA stability.