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In genomic selection (GS) DNA markers and trait data are integrated in a model that then predicts genomic-estimated breeding values (GEBV’s) for individuals using DNA marker information alone, improving breeding efficiency. We assessed a genomic breeding strategy (APWFGS) for improving dry matter yield (DMY) in perennial ryegrass. In APWFGS the best-performing half-sibling families (HS) are identified using phenotypic data and GS is used to select the best individuals within those HS. Four selections were made from three breeding populations: Base (random sample of plants from all HS), HSP (random sample from the six phenotypically-best HS), APWFGS and APWFGS-L (top or bottom 5% of plants, respectively, selected by GEBV from the six HS). Selected plants were polycrossed, creating 12 experimental synthetics that were evaluated as sown rows for DMY (n=7 harvests) in field trials at two locations over 18 months. In each population, mean DMY across locations and harvests showed a trend of APWFGS> HSP>Base. Averaged across all populations, APWFGS increased DMY by 43% (P

The evolution of peptidomimetic hybrid molecules for preoperative imaging and guided surgery targeting the prostate-specific membrane antigen (PSMA) significantly progressed over the past few years, and some approaches are currently being evaluated for further clinical translation. However, accumulation in nonmalignant tissue such as kidney, bladder, spleen, or liver might limit tumor-to-background contrast for precise lesion delineation, particularly in a surgical setting. To overcome these limitations, a rational linker design aims at the development of a second generation of PSMA-11–based hybrid molecules with an enhanced pharmacokinetic profile and improved imaging contrast. Methods: A selection of rationally designed linkers was introduced to the PSMA-targeting hybrid molecule Glu-urea-Lys-HBED-CC-IRDye800CW, resulting in a second-generation peptidomimetic hybrid molecule library. The biologic properties were investigated in cell-based assays. In a preclinical proof-of-concept study with the radionuclide (68)Ga, the impact of the modifications was evaluated by determination of specific tumor uptake, pharmacokinetics, and fluorescence imaging in tumor-bearing mice. Results: The modified hybrid molecules carrying various selected linkers revealed high PSMA-specific binding affinity and effective internalization. The highest tumor-to-background contrast of all modifications investigated was identified for the introduction of a histidine- (H) and glutamic acid (E)–containing linker ((HE)(3)-linker) between the PSMA-binding motif and the chelator. In comparison to the parental core structure, uptake in nonmalignant tissue was significantly reduced to a minimum, as exemplified by an 11-fold reduced spleen uptake from 38.12 ± 14.62 percentage injected dose (%ID)/g to 3.47 ± 1.39 %ID/g (1 h after injection). The specific tumor uptake of this compound (7.59 ± 0.95 %ID/g, 1 h after injection) was detected to be significantly higher than that of the parental tracer PSMA-11. These findings confirmed by PET and fluorescence imaging are accompanied by an enhanced pharmacokinetic profile with accelerated background clearance at early time points after injection. Conclusion: The novel generation of PSMA-targeting hybrid molecules reveals fast elimination, reduced background organ enrichment, and high PSMA-specific tumor uptake meeting the key demands for potent tracers in nuclear medicine and fluorescence-guided surgery. The approach’s efficacy in improving the pharmacokinetic profile highlights the strengths of rational linker design as a powerful tool in strategic hybrid-molecule development.

Objectives To investigate plaque inhibition of 0.1% octenidine mouthwash (OCT) vs. placebo over 5 days in the absence of mechanical plaque control. Materials and methods For this randomized, placebo-controlled, double-blind, parallel group, multi-center phase 3 study, 201 healthy adults were recruited. After baseline recording of plaque index (PI) and gingival index (GI), collection of salivary samples, and dental prophylaxis, subjects were randomly assigned to OCT or placebo mouthwash in a 3:1 ratio. Rinsing was performed twice daily for 30 s. Colony forming units in saliva were determined before and after the first rinse. At day 5, PI, GI, and tooth discoloration index (DI) were assessed. Non-parametric van Elteren tests were applied with a significance level of p Results Treatment with OCT inhibited plaque formation more than treatment with placebo (PI: 0.36 vs. 1.29; p p = 0.003) and salivary bacterial counts (2.73 vs. placebo 0.24 lgCFU/ml; p p = 0.0011). Mild tongue staining and dysgeusia occurred. Conclusions OCT 0.1% mouthwash inhibits plaque formation over 5 days. It therefore can be recommended when regular oral hygiene is temporarily compromised. Clinical relevance When individual plaque control is compromised, rinsing with octenidine mouthwash is recommended to maintain healthy oral conditions while side effects are limited.

Dysfunctional mitochondria are linked to several neurodegenerative diseases. Metabolic defects, a symptom which can result from dysfunctional mitochondria, are also present in spinocerebellar ataxia type 3 (SCA3), also known as Machado–Joseph disease, the most frequent, dominantly inherited neurodegenerative ataxia worldwide. Mitochondrial dysfunction has been reported for several neurodegenerative disorders and ataxin-3 is known to deubiquitinylate parkin, a key protein required for canonical mitophagy. In this study, we analyzed mitochondrial function and mitophagy in a patient-derived SCA3 cell model. Human fibroblast lines isolated from SCA3 patients were immortalized and characterized. SCA3 patient fibroblasts revealed circular, ring-shaped mitochondria and featured reduced OXPHOS complexes, ATP production and cell viability. We show that wildtype ataxin-3 deubiquitinates VDAC1 (voltage-dependent anion channel 1), a member of the mitochondrial permeability transition pore and a parkin substrate. In SCA3 patients, VDAC1 deubiquitination and parkin recruitment to the depolarized mitochondria is inhibited. Increased p62-linked mitophagy, autophagosome formation and autophagy is observed under disease conditions, which is in line with mitochondrial fission. SCA3 fibroblast lines demonstrated a mitochondrial phenotype and dysregulation of parkin-VDAC1-mediated mitophagy, thereby promoting mitochondrial quality control via alternative pathways.

This study aimed to investigate associations between psychosocial factors, obesity, and oral health in a study population of 10- to 18-year-old adolescents who participated in the LIFE Child study. Psychosocial information (socioeconomic status (SES) based on parents’ education, occupation and household income, Strengths and Difficulties Questionnaire (SDQ), health-related quality of life) and physical activity behavior were obtained. Nutritional status was classified based on age- and sex-adjusted body mass index into underweight, overweight, normal weight and obese. Clinical dental examinations were performed and scored with respect to caries experience (CE), oral hygiene (OH), and periodontal status (periodontal health score: PERIO-S). Age-adjusted regression analysis under the assumption of a double Poisson distribution was performed with and without adjusting for SES (α = 5%). A total of 1158 study participants (590 girls, 568 boys; mean age 13.2 ± 2.3 years) were included (17.2% were classified as obese). CE was 20% higher for moderate and 60% higher for low SES compared to high SES (p < 0.05). PERIO-S was 10% higher for moderate and 30% higher for low compared to high SES (p < 0.05). Poor OH was associated with higher CE (Ratio R = 2.3, p < 0.0001) and PERIO-S (R = 3.1, p < 0.0001). Physical activity in a sports club was associated with lower CE-S and PERIO-S (R = 0.85, p < 0.001). Obesity was associated with increased CE (R = 1.3, p < 0.001) compared to normal weight. For low but not high SES, more reported difficulties were associated with higher CE. In conclusion, low SES, poor OH, and obesity are associated with unfavorable oral health conditions, whereas physical activity and high SES are potentially protective.

Aberrant O-GlcNAcylation, a protein posttranslational modification defined by the O-linked attachment of the monosaccharide N-acetylglucosamine (O-GlcNAc), has been implicated in neurodegenerative diseases. However, although many neuronal proteins are substrates for O-GlcNAcylation, this process has not been extensively investigated in polyglutamine disorders. We aimed to evaluate the enzyme O-GlcNAc transferase (OGT), which attaches O-GlcNAc to target proteins, in Machado-Joseph disease (MJD). MJD is a neurodegenerative condition characterized by ataxia and caused by the expansion of a polyglutamine stretch within the deubiquitinase ataxin-3, which then present increased propensity to aggregate. By analyzing MJD cell and animal models, we provide evidence that OGT is dysregulated in MJD, therefore compromising the O-GlcNAc cycle. Moreover, we demonstrate that wild-type ataxin-3 modulates OGT protein levels in a proteasome-dependent manner, and we present OGT as a substrate for ataxin-3. Targeting OGT levels and activity reduced ataxin-3 aggregates, improved protein clearance and cell viability, and alleviated motor impairment reminiscent of ataxia of MJD patients in zebrafish model of the disease. Taken together, our results point to a direct interaction between OGT and ataxin-3 in health and disease and propose the O-GlcNAc cycle as a promising target for the development of therapeutics in the yet incurable MJD.

Periodontitis is an inflammatory disease of high prevalence and, thus, of potential relevance to the management of blood donation.The aim of this cross-sectional study was to assess periodontal health and its associations to common blood parameters, as well as questionnaire-based periodontitis screening in blood donors.Generally healthy blood donors were recruited and underwent oral examination. Thereby, the decayed-, missing- and filled-teeth index (DMF-T) and periodontal status, including periodontal probing depth and clinical attachment loss, were assessed. Based on periodontal status, periodontitis severity was classified into no/mild, moderate or severe. Six yes/no questions regarding periodontal complaints and history were asked. Furthermore, common blood parameters were analysed.A total of 148 participants (mean age 53·33 years) were included. The DMF-T was 15·28 ± 6·44. Nearly three quarters of participants suffered from a periodontitis (moderate 59·5% and severe 14·8%, total periodontitis 74·3%). Periodontitis severity was associated with the history of dental visits caused by periodontal complaints (P 0·01) and previous periodontal therapy (P 0·01). Only procalcitonin was initially found to be associated with blood periodontitis severity (P = 0·02). This observation was not confirmed by post-hoc testing between subgroups (PThe prevalence of periodontitis in German blood donors is high. However, further studies with sensitive testing of bacteria in peripheral blood are required in order to determine the relevance of this result for the safety of blood components.

The aim of this cross-sectional study was to investigate associations between salivary active matrix-metalloproteinase 8 (aMMP-8) and periodontitis severity, potentially periodontal pathogenic bacteria as well as blood parameters in generally healthy participants. Therefore, 188 participants with a mean age of 48.9 ± 8 years were examined. The periodontitis severity was assessed based on periodontal probing depth and clinical attachment loss. Both, aMMP-8 and microbiological analysis were performed using a validated, commercially available test system. Blood values were utilized from regular differential blood count. The aMMP-8 findings were associated with the periodontitis severity (P 0.05). In conclusion, salivary aMMP-8 findings seem to reflect periodontal disease severity as a result of an immunoreaction, especially against bacteria with high periodontal pathogenic potential.

Objective To investigate the genetic and epigenetic differences between human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) and HPV-negative OPSCC. Methods Microarray data of HPV-positive and -negative OPSCC were retrieved from NCBI GEO datasets. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) were identified by performing differential expression analysis. A functional enrichment analysis was performed to explore the biological processes and signaling pathways that DEGs and DE-miRNAs were involved in, respectively. A protein-protein interaction (PPI) network of DEGs was constructed to identify hub genes. miRNA-target network and miRNA-miRNA functional synergistic network were each constructed in order to identify risk-marker miRNAs. An miRNA-target-pathway network was constructed in order to explore the function of identified risk-marker miRNAs. Results Microarray data from 3 datasets (GSE39366, GSE40774, and GSE55550) was included and analyzed. The PPI network identified 3 hub genes (VCAM1, UBD, and RPA2). MiR-107 and miR-142-3p were found to play the most significant role in both the DE-miRNA-target network as well as in the miRNA-miRNA functional synergistic network. MiR-107 was involved in HPV-induced tumorigenesis by targeting many genes (CAV1, CDK6, MYB, and SERPINB5) and regulating the p53 signaling pathway, the PI3K-Akt signaling pathway, and the autophagy pathway. In addition, miR-142-3p was implicated in HPV-induced tumorigenesis by targeting the PPFIA1 gene and regulating transcriptional dysregulation and other cancerous pathways. Conclusion Three genes (VCAM1, UBD, and RPA2), two miRNAs (miR-107 and miR-142-3p), and four pathways (p53, PI3K-Akt, autophagy, and transcription dysregulation in cancer) were identified to play critical roles in distinguishing HPV-positive OPSCC from HPV-negative OPSCC.

Aberrant O-GlcNAcylation, a protein posttranslational modification defined by the O-linked attachment of the monosaccharide N-acetylglucosamine (O-GlcNAc), has been implicated in neurodegenerative diseases. However, although many neuronal proteins are substrates for O-GlcNAcylation, this process has not been extensively investigated in polyglutamine disorders. We aimed to evaluate the enzyme O-GlcNAc transferase (OGT), which attaches O-GlcNAc to target proteins, in Machado–Joseph disease (MJD). MJD is a neurodegenerative condition characterized by ataxia and caused by the expansion of a polyglutamine stretch within the deubiquitinase ataxin-3, which then present increased propensity to aggregate. By analyzing MJD cell and animal models, we provide evidence that OGT is dysregulated in MJD, therefore compromising the O-GlcNAc cycle. Moreover, we demonstrate that wild-type ataxin-3 modulates OGT protein levels in a proteasome-dependent manner, and we present OGT as a substrate for ataxin-3. Targeting OGT levels and activity reduced ataxin-3 aggregates, improved protein clearance and cell viability, and alleviated motor impairment reminiscent of ataxia of MJD patients in zebrafish model of the disease. Taken together, our results point to a direct interaction between OGT and ataxin-3 in health and disease and propose the O-GlcNAc cycle as a promising target for the development of therapeutics in the yet incurable MJD.

International audience; When data on the degradation of a chemical substance have been collected in a number of environmental media (e.g., in different soils), two strategies can be followed for data evaluation. Currently, each individual dataset is evaluated separately, and representative degradation parameters are obtained by calculating averages of the kinetic parameters. However, such averages often take on unrealistic values if certain degradation parameters are ill-defined in some of the datasets. Moreover, the most appropriate degradation model is selected for each individual dataset, which is time consuming and then requires workarounds for averaging parameters from different models. Therefore, a simultaneous evaluation of all available data is desirable. If the environmental media are viewed as random samples from a population, an advanced strategy based on assumptions about the statistical distribution of the kinetic parameters across the population can be used. Here, we show the advantages of such simultaneous evaluations based on nonlinear mixed-effects models that incorporate such assumptions in the evaluation process. The advantages of this approach are demonstrated using synthetically generated data with known statistical properties and using publicly available experimental degradation data on two pesticidal active substances. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

This study investigated utilisation behaviour of the dentist compared to general practitioners (GP) and medical specialists in a German cohort under consideration of risk indicators for irregular dental attendance.Analysis of the results of the population-based LIFE-Adult-Study (Leipzig, Germany) was performed. A total of 2231 participants of the LIFE-Adult-Study were randomly selected to complete the relevant questionnaire, considering medical attendance behaviour. Associations of self-reported medical conditions, including dentaland medical attendance, sociodemographic factors, as well as self-reported general health status and oral health complaints were determined.Of the 2231 participants who were included in the analysis, 14.2% reported not to have visited the dentist during the preceding 12 months. There could be shown a more selective utilisation behaviour towards medical services in smokers, men, low socioeconomic status and depression. Women were more likely to attend the dentist than men (OR = 1.8, CI = 1.4-2.3). Smoking (OR = 0.7, CI = 0.6-1.0), low socioeconomic status (OR = 0.6, CI = 0.4-0.8) and depression (OR = 0.6, CI = 0.4-0.9) were related to less dental attendance. Additionally, persons who do not visit the dentist regularly showed less attendance of the GP as well as medical specialists (p0.05). Depression could be shown to be an additional risk factor for unfavourable utilisation behaviour towards the dentist.The results showed differences in dental and medical attendance, depending on different patient-related factors. Focusing attention towards high-risk groups might improve dental as well as medical utilisation behaviour, and therefore health status as well.

Objectives This in vivo study compared the antibacterial effect of a self-etch adhesive with and without the brominated monomer 12-methacryloyloxydodecyl-pyridinium bromide (MDPB) on carious dentin after selective caries removal. Methods 10 patients showing deep primary carious lesions at two posterior teeth without pulpal symptoms were included. At visit I, carious tissue was selectively removed and carious dentin was sampled with a sterile roundbur (Komet No. 18). One cavity was restored with composite (SDR, Ceram X; DENTSPLY DeTrey) using an MDPB-containing self-etch adhesive (Clearfil Protect Bond, Kuraray Noritake; PB). The other restoration served as a control (Clearfil SE Bond II, Kuraray Noritake; SE). At visit II after 8 weeks, carious dentin was sampled again. Bacterial growth in carious dentin was differentiated using microbial cultivation. Bacterial DNA from intact cells and cell-free DNA were quantified using 16S rRNA gene-based real-time PCR and the microbial community composition was analyzed by amplicon deep-sequencing. Wilcoxon test was applied for statistical analysis. Results Both treatments showed a decrease of intact bacterial cells in carious dentin at visit II compared to visit I (PB: visit I: 1.1*106, visit II: 1.7*105 (p = 0.03); SE: visit I: 1.1*107, visit II = 2.4*105 (p = 0.002)). No statistically significant reduction of cell-free bacterial DNA was detected (PB: visit I: 6.1*105, visit II: 1.6*105 (p = 0.08); SE: visit I: 5.3*105, visit II: 2.9*105 (p = 0.10)). The decrease of intact cell-derived (p = 0.371) and cell-free DNA (p = 0.455) did not differ significantly between PB and SE. Lactobacillus was most abundant within the microbial community at both visits. Alpha-diversity was not affected by treatment and samples showed high intra- and interindividual diversity. Conclusion and clinical significance Both self-etch adhesives have an antibacterial effect due to a decrease of bacterial DNA after selective caries removal. However, the results do not reveal any additional antibacterial effect by MDPB. The study is registered with the German Clinical Trials Register (DRKS00011532).

Objective The aim of this in vitro study was to evaluate the ability of optical coherence tomography (OCT) to display calculus on root surfaces. Material and methods Ten teeth with calculus on the root surface were embedded in resin, omitting the root surface. A region of interest (ROI) was marked by small drill holes coronally and apically of the calculus and imaged by spectral-domain optical coherence tomography ([SD OCT], Telesto SP5, centre wavelength 1310 nm) and light microscopy (LM). To evaluate the impact of different fluids on calculus visualisation, using OCT, root surfaces were covered by a layer of NaCl and blood and displayed by OCT. Subsequently, teeth were completely covered with resin and sectioned for histological evaluation. Within the ROI, lengths of root surface and calculus were measured by LM and OCT, and the ratio [%] was calculated. In addition, at three sites of each ROI, agreement of presence and length of calculus was evaluated. Both methods were compared using Pearson’s correlation. Results Regarding the presence of calculus, agreement between LM and OCT was strong (κi = 0.783, p = 0.033), and measurements regarding the length of the calculus were strongly correlated (ri >0.906; pi Conclusion Calculus on the root surface can be displayed by SD-OCT, which therefore may be suited as imaging technology for subgingival calculus in periodontal pockets.

Objectives To analyze bioinformatic datasets for detecting genetic and epigenetic mechanisms shared by chronic periodontitis (CP) and oral squamous cell carcinoma (OSCC). Materials and methods Datasets from GEO and TCGA databases reporting mRNAs, miRNAs or methylation expression in human CP and OSCC tissues were analyzed. Differential expression, functional enrichment and protein-protein interaction (PPI) network analyses were performed. Differentially expressed miRNAs (DEmiRNAs) and genes (DEG) in CP and OSCC were determined. DEmiRNA-target and DEmiRNA-DEG networks were constructed. Directly and indirectly interacting cross-talk genes were screened, and their prediction accuracy and association with OSCC prognosis was determined. Results 3 DE-miRNAs (miR-375, miR-3609 and miR-3652) expressed in both CP and OSCC critically regulated most DEGs. Among 12 directly interacting cross-talk genes, NCAPH was significantly related with the prognosis of OSCC. NR2F2 had highest differential expression in CP and OSCC. Among 4 cross-talk genes (FN1, MPPED1, NDEL1, and NR2F2) differentially expressed in CP, 3 (FN1, MPPED1, NDEL1) were also expressed in OSCC. Among 12 indirectly interacting cross-talk genes differentially expressed in OSCC, 3 genes (CDCA8, HIST1H3J, and RAD51) were significantly related to its prognosis. Significant pathways involved in CP and OSCC included: chemokine receptors, class I PI3K signaling events, epithelial-to-mesenchymal transition and signaling events by VEGFR1 and VEGFR2, EGF receptor (ErbB1). Conclusion Bioinformatic analysis of available datasets implicated 1 directly interacting cross-talk gene (NCAPH), 4 indirectly interacting cross-talk genes (NCAPH, NR2F2, FN1, and MPPED1) and 3 DE-miRNAs (hsa-miR-375, miR-3609 and miR-3652) as shared genetic and epigenetic expression patterns between CP and OSCC.

The aim of this study was the investigation of concentration and prevalence of selected periodontal pathogenic bacteria and concentration of active matrix metalloproteinase-8 (aMMP-8) within a group of patients with inflammatory bowel diseases (IBD) and to compare the results with a group of healthy control subjects (HC).Fifty-nine IBD patients with Crohn`s disease (CD, n = 30) or ulcerative colitis (UC, n = 29) and 59 HC were included in this cross-sectional study. Based on periodontal probing depth (PD) and clinical attachment level (CAL), periodontitis was classified as healthy/mild, moderate, or severe. aMMP-8 was analyzed from gingival crevicular fluid using enzyme linked immunosorbent assay. Eleven selected periodontal pathogenic bacteria were analyzed in subgingival plaque samples using polymerase chain reaction.IBD patients showed higher CAL (P 0.01), more severe periodontitis (P = 0.04), gingival bleeding (P 0.01) and aMMP-8 concentration (P 0.01) than HC. Only in CD, increasing severity of periodontitis was associated with an increase in aMMP-8 concentration (P = 0.02). The prevalences of Eubacterium nodatum and Eikenella corrodens were significantly lower in IBD compared to HC (P = 0.01). Additionally, the prevalence of Eikenella corrodens was significantly higher in CD compared to the UC group (P = 0.04). Further statistically significant differences in selected bacteria between IBD and HC or CD and UC groups could not be found (P 0.05).The results reveal changes in host immune response of IBD patients in terms of aMMP-8. Only in CD increasing aMMP-8 was associated with severity of periodontal disease. The role of periodontal pathogenic bacteria in the interrelationship between IBD and periodontitis remains unclear.

Recent literature reveals worse periodontal health condition in ankylosing spondylitis (AS). However, roles of AS-related parameters, periodontal condition, and their association appear unclear. This cross-sectional study aimed at investigating dental and periodontal health as well as potentially periodontal pathogenic bacteria in patients with AS compared to healthy control subjects (HC). Dental examination comprised dental findings (DMF-T), periodontal probing depth (PPD), bleeding on probing, clinical attachment loss (CAL), papillary bleeding index, and microbiological analysis based on polymerase chain reaction of selected potentially periodontal pathogenic bacteria. Classification of periodontitis severity was based on PPD and/or CAL and divided into no/mild, moderate, and severe periodontitis. 52 participants with AS and 52 HC were included. 96% of the AS group and 75% of HC had moderate to severe periodontitis (moderate: AS = 26, HC = 34; severe: AS = 23, HC = 5; p

Antimicrobial peptides (AMPs) play a critical role in controlling innate and acquired immune responses. Local dysregulation of AMP is implicated in the pathogenesis of periodontal diseases as a response to periodontal pathogen challenge. Changes in AMP expression also characterize tobacco smoking, diabetes mellitus, obesity and rheumatoid arthritis, which are established risk factors of periodontal diseases, suggesting AMP may act as putative mechanistic links between these. The aim was to evaluate and summarize critically the current evidence pertaining to interrelationships between AMPs, periodontal diseases and selected periodontal disease risk factors. General and theme specific keywords were used to search the PUBMED database for studies relevant to AMP, periodontal diseases, smoking, diabetes mellitus, obesity and rheumatoid arthritis and critically reviewed. A total of 131 abstracts and 119 full text articles were screened for relevance; 13 studies were selected for inclusion after critical review. Local AMP dysregulation characteristic to periodontal diseases appears to occur within a broader landscape of complex systemic immune perturbations independently induced by smoking, metabolic and rheumatoid disease. The nature of these interactions and mechanistic pathways involved are inadequately understood. AMPs could be possible mechanistic interlinks between periodontal diseases and its risk factors. However, such evidence is very limited and more in vivo and in vitro studies are necessary to clarify the nature of such relationships. A greater understanding of AMPs as shared mediators is essential for unraveling their value as therapeutic or biomarker candidates.

The aim of this randomized clinical study was to detect the effect of an instruction within a group using oscillating-rotating (OR), sonic-active (SA), or manual toothbrushes (MTB) in young, oral healthy adults.One hundred fifty participants were randomly assigned into six groups (n = 25): with (OR-I, SA-I, MTB-I) and without instruction (OR-NI, SA-NI, MTB-NI). Participants in I subgroups received one standardized instruction of the toothbrush system. At baseline (t0), after 2 (t1), 4 (t2), and 12 weeks (t3), plaque indices including modified Quigley-Hein Index (QHI) and Marginal Plaque Index (MPI) as well as inflammation indices including Papilla Bleeding Index (PBI) and Gingival Index (GI) were assessed. Kruskal-Wallis test, Friedman test, and chi-square or Fisher's exact test (p 0.05) were used for statistical analysis.One hundred thirty-one participants completed the follow-up and were analyzed: OR-I = 21, OR-NI = 22, SA-I = 22, SA-NI = 22, MTB-I = 22, and MTB-NI = 22. Within groups between t0 and t3, OR and SA systems showed a significant plaque reduction, irrespective of instruction (pThe used toothbrush as well as the presence or absence of a single brush-specific instruction has no influence on plaque removal and reduction of gingival inflammation in young, oral healthy adults in an observation period of 12 weeks.A single instruction might bring no benefit in this patient group, independently of the used toothbrush system.

68Ga-Glu-urea-Lys-(Ahx)-HBED-CC (68Ga-PSMA-11) represents a successful radiopharmaceutical for PET/CT imaging of prostate cancer. Further optimization of the tumor-to-background contrast might significantly enhance the sensitivity of PET/CT imaging and the probability of detecting recurrent prostate cancer at low PSA values. This study describes the advantage of histidine (H)/glutamic acid (E) and tryptophan (W)/glutamic acid (E) containing linkers on the pharmacokinetic properties of 68Ga-PSMA-11. The tracers were obtained by a combination of standard Fmoc-based solid-phase synthesis and copper(I)-catalyzed azide–alkyne cycloaddition. Their 68Ga complexes were compared to the clinical reference 68Ga-PSMA-11 with respect to cell binding, effective internalization, and tumor targeting properties in LNCaP-bearing balb/c nu/nu mice. The introduction of (HE)i (i = 1–3) or (WE)i (i = 1–3) into PSMA-11 resulted in a significantly changed biodistribution profile. The uptake values in kidneys, spleen, liver, and ...