Influence of physical activity on periodontal health in patients with type 2 diabetes mellitus. A blinded, randomized, controlled trial.

OBJECTIVES: The aim was to investigate the effect of physical activity on periodontal health and HbA1c levels in patients with type 2 diabetes mellitus (T2DM) over a period of 6 months. MATERIALS AND METHODS: Thirty-seven patients with non-insulin-dependent T2DM were included in the study. The intervention group (n=20) performed physical activity over a period of 6 months. The control group (n=17) did not receive any intervention. Baseline and final examinations included dental parameters and concentrations of glycosylated hemoglobin (HbA1c) and high-sensitivity C-reactive protein (hsCRP). RESULTS: Physical activity showed a positive effect on periodontal health. Both the BOP (p= 0.005) and the severity of periodontitis (p= 0.001) were significantly reduced in the intervention group compared to the control group. Furthermore, HbA1c levels were reduced (p= 0.010) significantly in the intervention group while hsCRP levels significantly increased in the control group (p= 0.04). CONCLUSIONS: Within the limitations of this randomized, controlled trial, physical activity over a period of 6 months is a health-promoting measure for patients with T2DM and improves both periodontal health and HbA1c concentrations.

The Influence of Connection on the Microleakage Development of Implant- Supported Fixed Bridges.

PURPOSE: If bacteria penetrate through the implant-abutment connection, they may initiate inflammatory reactions in the peri-implant tissue. It seems that the type of connection plays a key role in the development of peri-implantitis. The aim of the present in vitro study was to compare the microleakage of implant-supported fixed complete arch bridges at the levels of abutment and implant. METHODS: Ten identical polyurethane model bases containing six implants each were produced using an edentulous model of the upper jaw. These models were prepared with two types of implant-supported complete arch prostheses. Five specimens were fixed at implant level and five at abutment level. The inner parts implants were inoculated with Escherichia coli (E.coli). Each implant was surrounded with closed bacteria-proof vessels to observe bacterial migration from the inner parts of implants to the nutrient solution. Samples of nutrient solution were taken at different time points up to 2 to 10 days and colony forming units were determined. RESULTS: The bacterial accumulation in the implant-supported bridges at the implant level was significantly lower than at the abutment-level (p=0.00953). CONCLUSION: For implant-supported fixed complete arch prostheses, bacterial accumulation was lower at the implant level than at the abutment-level.

Synthetic anti-endotoxin peptides interfere with Gram-positive and Gram-negative bacteria, their adhesion and biofilm formation on titanium.

AIMS: Implant-associated infections arise from the formation of bacterial biofilms, which are difficult to be treated with conventional antibiotics. Therefore, there is a need for new implant functionalizations, which inhibit biofilm formation. The aim of the present study was to characterize the effect of synthetic peptides to assess their applicability for this purpose. METHODS AND RESULTS: Two synthetic anti-endotoxin peptides, Pep19-2.5 and Pep19-4LF (Aspidasept I and II) were tested against both Gram-positive (Staphylococcus aureus and Streptococcus oralis) and Gram-negative (Pseudomonas aeruginosa and Aggregatibacter actinomycetemcomitans) bacteria associated with implant infections. Their activity was evaluated against different states of biofilm formation on the implant material titanium using CFU, live/dead fluorescence staining and confocal microscopy. Both peptides inhibited planktonic bacteria growth, impacted initial bacterial adhesion, reduced biofilm volume and increased the proportion of dead cells. Additionally, cytotoxicity analyses showed that neither peptide harmed human gingival fibroblasts nor osteoblasts at lower concentrations. CONCLUSION: A concentration-dependent antibacterial activity of both peptides against biofilms of four clinically relevant bacteria could be demonstrated. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study serve as a promising basis for the improvement of these peptides in order to finally achieve a peptide-equipped antibacterial implant surface.

Epidemiology and risk factors of peri-implantitis: A systematic review.

The purpose of this systematic review and meta-analysis was to assess the prevalence, incidence and risk factors of peri-implantitis in the current literature. An electronic search was performed to identify publications from January 1980 until March 2016 on 9 databases. The prevalence and incidence of peri-implantitis were assessed in different subgroups of patients and the prevalences were adjusted for sample size (SSA) of studies. For 12 of 111 identified putative risk factors and risk indicators, forest plots were created. Heterogeneity analysis and random effect meta-analysis were performed for selected potential risk factors of peri-implantitis. The search retrieved 8357 potentially relevant studies. Fifty-seven studies were included in the systematic review. Overall, the prevalence of peri-implantitis on implant level ranged from 1.1% to 85.0% and the incidence from 0.4% within 3 years, to 43.9% within 5 years, respectively. The median prevalence of peri-implantitis was 9.0% (SSA 10.9%) for regular participants of a prophylaxis program, 18.8% (SSA 8.8%) for patients without regular preventive maintenance, 11.0% (SSA 7.4%) for non-smokers, 7.0% (SSA 7.0%) among patients representing the general population, 9.6% (SSA 9.6%) for patients provided with fixed partial dentures, 14.3% (SSA 9.8%) for subjects with a history of periodontitis, 26.0% (SSA 28.8%) for patients with implant function time ≥5 years and 21.2% (SSA 38.4%) for ≥10 years. On a medium and medium-high level of evidence, smoking (effect summary OR 1.7, 95% CI 1.25-2.3), diabetes mellitus (effect summary OR 2.5; 95% CI 1.4-4.5), lack of prophylaxis and history or presence of periodontitis were identified as risk factors of peri-implantitis. There is medium-high evidence that patient's age (effect summary OR 1.0, 95% CI 0.87-1.16), gender and maxillary implants are not related to peri-implantitis. Currently, there is no convincing or low evidence available that identifies osteoporosis, absence of keratinized mucosa, implant surface characteristics or edentulism as risk factors for peri-implantitis. Based on the data analyzed in this systematic review, insufficient high-quality evidence is available to the research question. Future studies of prospective, randomized and controlled type including sufficient sample sizes are needed. The application of consistent diagnostic criteria (eg, according to the latest definition by the European Workshop on Periodontology) is particularly important. Very few studies evaluated the incidence of peri-implantitis; however, this study design may contribute to examine further the potential risk factors.

Streptococcus mitis and Gemella haemolysans were simultaneously found in atherosclerotic and oral plaques of elderly without periodontitis-a pilot study.

OBJECTIVES: Local infections may contribute to the initiation and progression of several clinical diseases in humans. Atherosclerotic plaques of subjects suffering from periodontitis are colonized by periopathogens; however, the presence of bacteria in atherosclerotic plaques in patients without severe forms of periodontitis is of high relevance for the general population. MATERIALS AND METHODS: Patients who were electively treated for atherosclerotic lesions of the carotid artery and without clinical signs of periodontitis were eligible for the study. Oral and atherosclerotic plaques were sampled, processed, and analyzed for their microbial composition by 454-sequencing. RESULTS: Seventeen patients were included in the analyses, and 76 % of all atherosclerotic plaque specimens were positive for bacterial DNA. In the oral plaques, 76,532 sequences were identified representing 1 phylum, 17 classes, 112 families, and 263 genera. In atherosclerotic plaques, 6112 sequences representing 1 phylum, 4 classes, 8 families, and 36 genera were found. The bacterial DNAs of the species Gemella haemolysans and Streptococcus mitis were simultaneously found in atherosclerotic as well as oral plaque samples of 3 patients. CONCLUSIONS: These results indicated that in subjects without periodontitis, the transmission of oral bacteria to atherosclerotic plaques of the carotid artery is a feasible event. CLINICAL RELEVANCE: The prevention of transient bacteremia from the oral cavity requires high levels of oral health.

Pain and discomfort following immediate and delayed loading by overdentures in the single mandibular implant study (SMIS).

OBJECTIVES: This randomized clinical trial compares immediate and delayed loading of single implants to support mandibular overdentures. The aim of this preliminary analysis is to test the hypothesis whether patients with immediate loading will experience less pain and discomfort through the intervention than patients with delayed loading. MATERIALS AND METHODS: Edentulous patients in nine German dental schools received a midline implant with a length of 11 mm. Implants with a minimum insertion torque of 30 Ncm and an implant stability quotient of ≥60 were randomly allocated to group A for immediate loading using ball attachments or to group B for delayed loading after 3 months. Patients completed questionnaires with 100-mm visual analogue scales about the items pain, pain during chewing, swelling, bleeding, and perception of the intervention at the day of surgery and 1, 2, 3, and 7 days, thereafter. Groups were compared by Wilcoxon-Mann-Whitney tests (P ≤ 0.05). RESULTS: The questionnaires of 81 patients in group A and 74 patients in group B were completed. The medians for pain and discomfort were moderate (<30). Participants of group A felt significantly more pain from the first day and more swelling from the third day after implantation than participants of group B. The individual perception of interventions showed no significant differences between groups. CONCLUSIONS: Immediate loading evoked more postoperative pain and swelling than the two stages of delayed loading. CLINICAL RELEVANCE: Immediate loading of a single mandibular midline implant supporting overdentures should be carefully considered.

Marginal fit of indirect composite inlays using a new system for manual fabrication.

AIM: This in vitro study compares a new system for manual chair side fabrication of indirect composite restorations, which uses silicone models after alginate impressions, to CAD/CAM-technology and laboratory manual production techniques. MATRIALS AND METHODS: and study design Each 10 composite inlays were fabricated using different types of production techniques: CAD/CAM- technology (A), the new inlay system (B), plaster model after alginate impression (C) or silicone impression (D). The inlays were adapted into a metal tooth and silicone replicas of the cement gaps were made and measured. Statistical analysis was performed using ANOVA and Tukey's test. Results and Statistics In group A the biggest marginal gaps (174.9µm ± 106.2µm) were found. In group B the gaps were significantly smaller (119.5 µm ± 90.6 µm) than in group A (p=0.035). Between groups C (64.6 µm ± 68.0µm) and D (58.2 µm ± 61.7 µm) no significant differences could be found (p=0.998), but the gaps were significantly smaller compared with group B. Conclusion Chairside manufacturing of composite inlays resulted in better marginal precision than CAD/CAM technology. In comparison to build restorations in a laboratory, the new system is a timesaving and inexpensive alternative. Nevertheless, production of indirect composite restorations in the dental laboratory showed the highest precision.

Synthesis of new carolacton derivatives and their activity against biofilms of oral bacteria.

Carolacton, a secondary metabolite isolated from the extracts of Sorangium cellulosum, causes membrane damage and cell death in biofilms of the caries- and endocarditis-associated bacterium Streptococcus mutans. Here, we report the total synthesis of several derivatives of carolacton. All new structural modifications introduced abolished its biological activity, including subtle ones, such as inversion of configuration at C9. However, a bicyclic bislactone derivative as well as the methyl ester of carolacton resulted in compounds with prodrug properties. Their inhibitory activity on S. mutans was proven to be based on enzymatic hydrolysis by S. mutans which provided native carolacton resulting in biofilm damage in vivo. Moreover, we demonstrate that carolacton acts also on S. gordonii, S. oralis and the periodontitis pathogen Aggregatibacter actinomycetemcomitans, causing elongated cells and growth inhibition.

Expression of antimicrobial peptides and interleukin-8 during early stages of inflammation: An experimental gingivitis study.

BACKGROUND AND OBJECTIVES: In the oral cavity, the epithelial surface is constantly exposed to a number of different microorganisms that are organized in a well-structured biofilm. The aim of this study was to monitor gingival expression of antimicrobial peptides (AMPs) and interleukin-8 (IL-8) in an early gingivitis model. MATERIAL AND METHODS: Experimental gingivitis was allowed to develop in healthy volunteers (n = 17). Bleeding on probing (BOP%) and gingival crevicular fluid volume (GCF) were assessed at baseline and day 1, 3, 5, 7 and 14. Expression of AMPs (human beta-defensin-2, hBD-2; CC-chemokine ligand 20, CCL20; psoriasin, pso/S100A7) and IL-8 was analyzed by immunohistochemistry in gingival biopsies. In addition, hBD-2 and IL-8 protein expression was monitored in GCF using the ELISA technology. RESULTS: Experimental gingivitis gradually developed with an increase in BOP scores and GCF volume over time. In GCF, elevated concentrations of hBD-2 and IL-8 were monitored at day 1, 5 and 7 (p ≤ 0.0002). Immunohistochemical analysis of gingival sections demonstrated increased staining for hBD-2 at day 3, whereas the CCL20, pso/S100A7, and IL-8 expression was increased at later time points (p < 0.05). CONCLUSION: For the first time, this study showed the time-dependent regulation of AMPs, following clinical signs of experimentally induced gingival inflammation. Differential temporal expression for AMPs may ensure a constant antimicrobial activity against changes in the bacterial composition of the growing dental biofilm.

Impact of loading protocol of a mandibular single implant-supported complete denture on oral health-related quality of life over a period of 5 years: A randomized controlled trial.

OBJECTIVES: The aim of the present study was to assess the long-term course of OHRQoL and the impact of the loading protocol in patients receiving a single mandibular implant supporting a complete denture over a period of five years. METHODS: In this multicenter RCT, a total of 158 edentulous patients were initially included and were randomly allocated immediately after placement of a mandibular midline implant to either immediate loading (IL) or to conventional loading (CL) with submerged healing. The assessment of OHRQoL was performed with the 49-item Oral Health Impact Profile (OHIP) at baseline and 1, 4, 12, 24, and 60 months after loading. At 5-year follow-up, 100 patients (mean age: 69.2 years; 45.0% female) with completed OHIP were available for analyses. A mixed-effects model with patients as random effect and an unstructured covariance matrix was developed to address repeated outcome measurement. RESULTS: The OHRQoL improved substantially after loading, indicated by a decrease of mean OHIP summary scores from 51.0 points at baseline, by 14.2 (95%-CI: 9.4 - 19.1; p<0.001) points to 37.2 points at 1-month follow-up, and by continuous improvement to 20.4 OHIP points at final follow-up. Considering constant treatment effects, the loading protocol had no significant effect on OHIP scores (-3.7, 95%-CI: -9.4 - 2.2; p = 0.204). Time effect was statistically significant with -0.21 (95%-CI: -0.28 - -0.15; p<0.001) points per month. CONCLUSION: Both the immediate and conventional loading of a single mandibular midline implant supporting a complete denture offer long-lasting high levels of OHRQoL, with no significant or clinically relevant long-term differences. CLINICAL SIGNIFICANCE: The study firstly presents long-term data for OHRQoL by investigating the loading protocol of single mandibular implant-supported complete dentures. Since immediate loading has been associated with a reduced implant survival rate for this concept, information on patient benefits is essential for evidence-based decision making.

[Clinical symptoms and diagnostic workup of allergic reactions on the oral mucosa]. / Klinische Symptomatik und Diagnostik allergischer Reaktionen der Mundschleimhaut.

Contact allergies at the oral mucosa are associated with diverse symptoms. In this article we focus on the contact allergy of delayed type. Oral mucosa changes including stomatitis or lichenoid inflammation can give first evidence for such a contact allergy. Subjective symptoms including pain, burning or dryness of the oral mucosa can be associated with a contact allergy but may also occur in other diseases which need to be excluded. The first step in the diagnosis of a contact allergy is the complete examination of the oral mucosa. Additionally, a careful history of the patient's oral care products, drugs and dental materials is important. If mucosal changes are present, a patch test is recommended for the diagnostic work up for contact allergy of delayed type. In case of a positive patch test reaction, a careful check for the clinical relevance is needed in order to have a clear recommendation for both patient and dentist e.g. if replacement of prosthetic materials is needed.

Microbial diversity of supra- and subgingival biofilms on freshly colonized titanium implant abutments in the human mouth.

Supra- and subgingival biofilm formation is considered to be mainly responsible for early implant failure caused by inflammations of periimplant tissues. Nevertheless, little is known about the complex microbial diversity and interindividual similarities around dental implants. An atraumatic assessment was made of the diversity of microbial communities around titanium implants by single strand conformation polymorphism (SSCP) analysis of the 16S rRNA gene amplicons as well as subsequent sequence analysis. Samples of adherent supra- and subgingival periimplant biofilms were collected from ten patients. Additionally, samples of sulcusfluid were taken at titanium implant abutments and remaining teeth. The bacteria in the samples were characterized by SSCP and sequence analysis. A high diversity of bacteria varying between patients and within one patient at different locations was found. Bacteria characteristic for sulcusfluid and supra- and subgingival biofilm communities were identified. Sulcusfluid of the abutments showed higher abundance of Streptococcus species than from residual teeth. Prevotella and Rothia species frequently reported from the oral cavity were not detected at the abutments suggesting a role as late colonizers. Different niches in the human mouth are characterized by specific groups of bacteria. Implant abutments are a very valuable approach to study dental biofilm development in vivo.

Stress analysis of an all-ceramic FDP loaded according to different occlusal concepts.

The aim of this study was to investigate the influence of four different occlusal concepts on stress distribution in a four-unit fixed dental prosthesis (FDP) made of zirconia. A three-dimensional finite element (FE) model was created and four model versions with between 15 and 42 contact points were developed. A force of 300 N was distributed over the chewing surface according to the different occlusal concepts and virtually applied perpendicularly to the occlusal plane in each version. Then, FE analysis was performed and stress distribution evaluated. Generally, highest tensile stresses were located at the point of load application within the veneering layer and ranged from 104 to 204 MPa. The highest tensile stresses within the framework were located at the basal side of the connectors and ranged between 12 and 39 MPa. This study shows that the distribution of occlusal contact points significantly influences the stresses induced by occlusal forces in four-unit all-ceramic fixed dental prostheses and strongly suggests that the number and distribution of occlusal contacts may be important to minimise fatigue effects caused by cycling.

Influence of the veneering process on the marginal fit of zirconia fixed dental prostheses.

Distortions in the marginal region during manufacture are detrimental to the long-term success of fixed dental prostheses (FDPs). The aim of the present in vitro study was to evaluate changes in marginal fit because of the veneering process of four-unit FDPs made from different zirconia materials. Two groups of FDPs with 10 specimens each were machined from white body zirconia blanks (VITA In-Ceram YZ Cubes, KaVo Everest ZS-Blanks) by means of computer-aided design/computer-aided manufacturing systems and subsequently sintered to their final density. The marginal and internal gaps of the frameworks were determined using a replica technique. Afterwards, frameworks were veneered with the recommended ceramics (VITA VM9, GC Initial Zr), and fitting accuracy was evaluated again. Statistical analyses were performed by Student's t-test with the level of significance chosen at 0.05. With one framework/veneering system (Everest ZS-Blanks/Initial Zr), both marginal gap (P = 0.019) and internal gap (P = 0.001) at the premolar retainer were significantly affected by the veneering process. The resulting distortions were directed towards the lumina of the retainers and the mean values of the measured gaps decreased by about 23.8 mum (marginal gap) and 27.3 mum (internal gap). For the other system (In-Ceram YZ Cubes/VM9), no distortions because of the veneering were found. The veneering of zirconia restorations may lead to significant changes in the marginal fit, while the combination of core and veneering material used influences the resulting distortions.

Short-term influence of lingual orthodontic therapy on microbial parameters and periodontal status. A preliminary study.

OBJECTIVE: To perform a preliminary study of the short-term effect of fixed, customized lingual orthodontic appliances on periodontal and microbial parameters. MATERIALS AND METHODS: The sample comprised 20 subjects (6 males and 14 females) with a mean age of 22.3 years +/- 8.6 years. Before (T(0)) and 4 weeks after placement (T(1)) of custom-made lingual appliances on the lower teeth only, plaque index (PI), probing pocket depth (PPD), and bleeding on probing (BOP) were measured. A 16S rRNA-based polymerase chain reaction (PCR) method was used to detect Aggregatibacter actinomycetemcomitans ( Aa ) and Porphyromonas gingivalis ( Pg ) in the crevicular fluid. To compare periodontal parameters on bonded lingual (testing) and unbonded palatal (control) and labial (control) sites between T(0) and T(1), the Wilcoxon test was applied. RESULTS: On the lingual aspects of bonded teeth, a significant increase of BOP (T(0): 23.4 +/- 22.5%; T(1): 46.2 +/- 23.5%; P = .001) and PI (T(0): 0.3 +/- 0.3; T(1): 1.0 +/- 0.7; P = .001) was observed, but no significant changes for PPD (T(0): 2.1 +/- 0.4 mm; T(1): 2.2 +/- 0.3 mm; P = .286) were found. On control sites, no significant changes were recorded for any periodontal parameter. Aa was found in 25% of the patients at baseline (5 subjects) and in 35% of the patients at T(1) (2 additional positive subjects), whereas Pg was found in 5% of the cohort at T(0) and at T(1) (same patient). CONCLUSIONS: Even in the short term, insertion of fixed lingual appliances induced a worsening of periodontal parameters restricted to bonded lingual sites.

Reduction of biofilm on orthodontic brackets with the use of a polytetrafluoroethylene coating.

SUMMARY: Treatment with fixed orthodontic appliances can cause enamel demineralization by increased biofilm adhesion. The purpose of the present study was to investigate whether a polytetrafluoroethylene (PTFE) coating reduces biofilm formation on orthodontic brackets. One PTFE-coated bracket and one uncoated stainless steel bracket were bonded symmetrically on the first or second (four maxillary and nine mandibular) primary molars in 13 adolescent patients (five females and eight males, aged 11.2 +/- 2.8 years; four dropouts) for 8 weeks. Quantitative biofilm formation on brackets was analysed with the Rutherford backscattering detection (RBSD) method, a scanning electron microscopy technique. A total of five RBSD micrographs were obtained per bracket with views from the buccal, mesial, distal, cervical, and occlusal aspects. A two-sided paired t-test was used to compare data. A P-value less than 0.05 was considered significant. Total biofilm formation was 4.0 +/- 3.6 per cent of the surface on the PTFE-coated brackets and 22.2 +/- 5.4 per cent on uncoated brackets. Differences between the two groups were statistically significant (P < 0.05). Pairwise comparison of biofilm formation with respect to location (buccal, mesial, distal, cervical, and occlusal) revealed a significantly lower biofilm accumulation on PTFE-coated brackets on all surfaces. The results indicate that PTFE coating of brackets reduces biofilm adhesion to a minimum and might have the potential to reduce iatrogenic side effects, e.g. decalcification during orthodontic treatment with fixed appliances.

Influence of lingual orthodontic therapy on microbial parameters and periodontal status in adults.

Insertion of fixed orthodontic appliances can induce an increase in oral biofilm and thereby cause inflammation of the periodontal tissues. The purpose of this study was to perform a longitudinal analysis of clinical and microbial parameters after insertion of lingual brackets. Bleeding on probing (BOP), plaque index (PI), and pocket probing depth (PPD) were measured in 10 adults (8 females and 2 males, aged 29.0 +/- 4.7 years) who received treatment with custom-made lingual appliances (Incognito/iBraces) before (T0) and 3 months after beginning of treatment (T1). No supportive dental prophylaxis was undertaken. In addition, a 16S rRNA-based polymerase chain reaction (PCR) method was used to detect Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) in the crevicular fluid. A Wilcoxon test was used to compare clinical parameters at the buccal (control) and lingual sites between T0 and T1. At T0, BOP was 12.4 +/- 8.2 per cent, PPD 2.1 +/- 0.3 mm, and PI 0.1 +/- 0.2 at the buccal sites and at T1 14.3 +/- 8.1 per cent, 2.1 +/- 0.2 mm and 0.1 +/- 0.2, respectively. At the lingual sites, BOP was 22.2 +/- 19.0 per cent, PPD 2.3 +/- 0.3 mm, and PI 0.1 +/- 0.2 at T0 and at T1 56.2 +/- 31.6 per cent, 2.9 +/- 0.3 mm, and 1.2 +/- 1.1, respectively. Differences between T0 and T1 were significant for clinical parameters only at the lingual sites. Aa was found in five patients at baseline and in four at T1, whereas Pg was found in one patient at T0 and in two at T1. Insertion of fixed lingual appliances without supportive dental prophylaxis induced a worsening of clinical parameters restricted to the lingual sites, whereas the relative prevalence of Aa and Pg remained unchanged.

The best from East and West? Acupuncture and medical training therapy as monotherapies or in combination for adult patients with episodic and chronic tension-type headache: study protocol for a randomized controlled trial.

BACKGROUND: This study aims to evaluate the feasibility and efficacy of a complex health intervention, based on the combination of conventional Western medicine and traditional Chinese medicine (TCM), in an outpatient department of a university hospital for patients with frequent episodic or chronic tension-type headaches. METHODS/DESIGN: This is a prospective randomized controlled pilot study with four balanced treatment arms (usual care, acupuncture, training, and training plus acupuncture). Each arm will have 24 patients. After the initial screening examination and randomization, a 6-week treatment period follows, with treatment frequencies decreasing at 2-week intervals. After completion of the intervention, two follow-up evaluations will be performed 3 and 6 months after the start of treatment. At predefined times, the various outcomes (pain intensity, health-related quality of life, pain duration, autonomic regulation, and heart rate variability) as well as the participants' acceptance of the complex treatment will be evaluated with valid assessment instruments (Migraine Disability Assessment, PHQ-D, GAD-7, and SF-12) and a headache diary. The acupuncture treatment will be based on the rules of TCM, comprising a standardized combination of acupuncture points and additional points selected according to individual pain localization. The training therapy comprises a combination of strength training, endurance training, and training to improve flexibility and coordination. Besides descriptive analyses of the samples, their comparability will be assessed using an analysis of variance (ANOVA) or chi-squared tests. Analyses will be performed on an intention-to-treat basis. Potential interaction effects will be calculated using a repeated-measures ANOVA to test the primary and secondary hypotheses. In supplementary analyses, the proportion of treatment responders (those with a 50% reduction in the frequency of pain episodes) will be determined for each treatment arm. DISCUSSION: This trial may provide evidence for the additive effects of acupuncture and medical training therapy as a combination treatment and may scientifically support the implementation of this complex health intervention. TRIAL REGISTRATION: Registered on 11 Feburary 2019. German Clinical Trials Register, DRKS00016723.

Survival and Complications of Single Dental Implants in the Edentulous Mandible Following Immediate or Delayed Loading: A Randomized Controlled Clinical Trial.

It was the aim of this 24-mo randomized controlled clinical trial to investigate whether the survival of a single median implant placed in the edentulous mandible to retain a complete denture is not compromised by immediate loading. Secondary outcomes were differences in prosthetic complications between the loading principles. Each of the 158 patients who received an implant was randomly assigned to the immediate loading group ( n = 81) or the delayed loading group ( n = 77). Recall visits were performed 1 mo after implant placement (for only the delayed loading group) and 1, 4, 12, and 24 mo after implant loading. Nine implants failed in the immediate loading group, all within the first 3 mo of implant loading, and 1 implant failed in the delayed loading group prior to loading. Noninferiority of implant survival of the immediate loading group, as compared with the delayed loading group, could not be shown ( P = 0.81). Consistent with this result, a secondary analysis with Fisher exact test revealed that the observed difference in implant survival between the treatment groups was indeed statistically significant ( P = 0.019). The most frequent prosthetic complications and maintenance interventions in the mandible were retention adjustments, denture fractures, pressure sores, and matrix exchanges. There was only 1 statistically significant difference between the groups regarding the parameter "fracture of the denture base in the ball attachment area" ( P = 0.007). The results indicate that immediate loading of a single implant in the edentulous mandible reveals inferior survival than that of delayed loading and therefore should be considered only in exceptional cases (German Clinical Trials Register: DRKS00003730).

Theoretical and experimental evidence for eliminating persister bacteria by manipulating killing timing.

Formation of a transient sub-population of bacteria, referred to as persisters, is one of the most important and least understood mechanisms that bacteria employ to evade elimination. Persister cells appear to be slow-growing bacteria that are broadly protected from a wide range of antibiotics. Using both theoretical and experimental methods, we show that alternating the application and withdrawal of antibiotics can be an effective treatment-as long as the timing of the protocol is estimated with precision. More specifically, we demonstrate that timing the alternating treatment based on theoretical predictions is confirmed using experimental observations. These results support a large class of theoretical studies that show that, even without complete understanding of the biological mechanisms, these models can provide insight into properties of the system.