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Introduction: The aim was to evaluate the suitability of paper points or endodontic nickel-titanium files to sample microorganisms for in vivo investigation of endodontic microbiota by 16S ribosomal DNA (rDNA) sequencing., Methods: Forty-five patients presenting clinical and radiological signs of apical periodontitis were recruited for sampling, giving their written informed consent. Glide paths were assessed using C-Pilot Files and K-Files under electronic root canal length control under aseptic conditions. Microbial samples were taken from 84 root canals in duplicate, the first sample with a sterile paper point (size 15), the second with a sterile file (size 20/.06). After DNA extraction, the hypervariable region V4 of the bacterial 16 S rRNA gene was amplified and sequenced (Illumina MiSeq). Sequencing data were trimmed with Cutadapt and exact amplicon sequence variants generated by DADA2. Taxonomy was assigned based on the Human Oral Microbiome Database (eHOMD). Statistical analysis of diversity parameters comprised Wilcoxon signed-rank tests and permutational analysis of variance (PERMANOVA). Compositional differences were evaluated by differential abundance analysis (DESeq2). Microbial contamination during the sampling process and analysis were evaluated., Results: Concerning alpha diversity, richness and dissimilarity differed nonsignificantly between paper point and instrument samples (P > .05), whereas a significant difference was observed in the Shannon index (P < .05). Regarding beta diversity, paper point and instrument samples presented with similar microbial community compositions (P = 1.0, PERMANOVA). Paper point controls contained significantly higher proportions of Pseudomonadales (P < .05)., Conclusions: Paper point and endodontic instrument sampling generate valid specimens for 16S rDNA community profiling. Endodontic instrument sampling is easier to execute and, therefore, could be the technique of choice., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Periodontitis, a prevalent chronic inflammatory disease, offers insights into the broader landscape of chronic inflammatory conditions. The progression and treatment outcomes of periodontitis are closely related to the oral microbiota's composition. Adjunctive systemic Amoxicillin 500 mg and Metronidazole 400 mg, often prescribed thrice daily for 7 days to enhance periodontal therapy's efficacy, have lasting effects on the oral microbiome. However, the precise mechanism through which the oral microbiome influences clinical outcomes in periodontitis patients remains debated. This investigation explores the pivotal role of the oral microbiome's composition in mediating the outcomes of adjunctive systemic antibiotic treatment., Methods: Subgingival plaque samples from 10 periodontally healthy and 163 periodontitis patients from a randomized clinical trial on periodontal therapy were analyzed. Patients received either adjunctive amoxicillin/metronidazole or a placebo after mechanical periodontal treatment. Microbial samples were collected at various intervals up to 26 months post-therapy. Using topic models, we identified microbial communities associated with normobiotic and dysbiotic states, validated with 86 external and 40 internal samples. Logistic regression models evaluated the association between these microbial communities and clinical periodontitis parameters. A Directed Acyclic Graph (DAG) determined the mediating role of oral microbiota in the causal path of antibiotic treatment effects on clinical outcomes., Results: We identified clear distinctions between dysbiotic and normobiotic microbial communities, differentiating healthy from periodontitis subjects. Dysbiotic states consistently associated with below median %Pocket Probing Depth ≥ 5 mm (OR = 1.26, 95% CI [1.14-1.42]) and %Bleeding on Probing (OR = 1.09, 95% CI [1.00-1.18]). Factors like microbial response to treatment, smoking, and age were predictors of clinical attachment loss progression, whereas sex and antibiotic treatment were not. Further, we showed that the oral microbial treatment response plays a crucial role in the causal effect of antibiotic treatment on clinical treatment outcomes., Conclusions: The shift towards a normobiotic subgingival microbiome, primarily induced by adjunctive antibiotics, underscores the potential for microbiome-targeted interventions to enhance therapeutic efficacy in chronic inflammatory conditions. This study reaffirms the importance of understanding the oral microbiome's role in periodontal health and paves the way for future research exploring personalized treatment strategies based on individual microbiome profiles. Video Abstract., (© 2024. The Author(s).)

Aim: To explore whether adjunctive antibiotics can relevantly influence long-term microbiota changes in stage III-IV periodontitis patients., Materials and Methods: This is a secondary analysis of a randomized clinical trial on periodontal therapy with adjunctive 500 mg amoxicillin and 400 mg metronidazole or placebo thrice daily for 7 days. Subgingival plaque samples were taken before and 2, 8, 14 and 26 months after mechanical therapy. The V4-hypervariable region of the 16S rRNA gene was sequenced with Illumina MiSeq 250 base pair paired-end reads. Changes at the ribosomal sequence variant (RSV) level, diversity and subgingival-microbial dysbiosis index (SMDI) were explored with a negative binomial regression model and non-parametric tests., Results: Overall, 50.2% of all raw reads summed up to 72 RSVs (3.0%) that were generated from 163 stage III-IV periodontitis patients. Of those, 16 RSVs, including Porphyromonas gingivalis, Tannerella forsythia and Aggregatibacter actinomycetemcomitans, changed significantly over 26 months because of adjunctive systemic antibiotics. SMDI decreased significantly more in the antibiotic group at all timepoints, whereas the 2-month differences in alpha and beta diversity between groups were not significant at 8 and 14 months, respectively., Conclusions: Mechanical periodontal therapy with adjunctive antibiotics induced a relevant and long-term sustainable change towards an oral microbiome more associated with oral health., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

We use different halido ligands to tune metal-metal interactions, nucleation pathways and hetero-seeded growth in supramolecular copolymerizations.

Supramolecular polymers (SPs) of d 8 transition metal complexes have received considerable attention by virtue of their rich photophysical properties arising from metal-metal interactions. However, thus far, the molecular design is restricted to complexes with chelating ligands due to their advantageous preorganization and strong ligand fields. Herein, we demonstrate unique pathway-controllable metal-metal-interactions and remarkable 3 MMLCT luminescence in SPs of a non-chelated Pt II complex. Under kinetic control, self-complementary bisamide H-bonding motifs induce a rapid self-assembly into non-emissive H-type aggregates (1A). However, under thermodynamic conditions, a more efficient ligand coplanarization leads to superiorly stabilized SP 1B with extended Pt⋅⋅⋅Pt interactions and remarkably long 3 MMLCT luminescence (τ 77 K =0.26 ms). The metal-metal interactions could be subsequently exploited to control the length of the emissive SPs using the seeded-growth approach., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

We reveal unique hydrogen (H-) bonding patterns and exploit them to control the kinetics, pathways and length of supramolecular polymers (SPs). New bisamide-containing monomers were designed to elucidate the role of competing intra- vs. intermolecular H-bonding interactions on the kinetics of supramolecular polymerization (SP). Remarkably, two polymerization-inactive metastable states were discovered. Contrary to previous examples, the commonly assumed intramolecularly H-bonded monomer does not evolve into intermolecularly H-bonded SPs via ring opening, but rather forms a metastable dimer. In this dimer, all H-bonding sites are saturated, either intra- or intermolecularly, hampering elongation. The dimers exhibit an advantageous preorganization, which upon opening of the intramolecular portion of the H-bonding motif facilitates SP in a consecutive process. The retardation of spontaneous self-assembly as a result of two metastable states enables length control in SP by seed-mediated growth., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The self-assembly of discrete molecular entities into functional nanomaterials has become a major research area in the past decades. The library of investigated compounds has diversified significantly, while the field as a whole has matured. The incorporation of metal ions in the molecular design of the (supra-)molecular building blocks greatly expands the potential applications, while also offering a promising approach to control molecular recognition and attractive and/or repulsive intermolecular binding events. Hence, supramolecular polymerization of metal-containing monomers has emerged as a major research focus in the field. In this perspective article, we highlight recent significant advances in supramolecular polymerization of metal-containing monomers and discuss their implications for future research. Additionally, we also outline some major challenges that metallosupramolecular chemists (will) have to face to produce metallosupramolecular polymers (MSPs) with advanced applications and functionalities., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We report on the synthesis of the first examples of 1,3-azaborinine derived oxindole systems, the BN-isosteres of the important compound class of the oxindoles. Hydroboration of terminal aryl acetylenes with FmesBH2, followed by treatment with 2 equiv. of a glycine ester derived isonitrile gave a small series of 1,3-azaborinine derived oxindoles. The new BN-oxindoles show interesting photophysical behavior.

Halogens play a crucial role in numerous natural processes and synthetic materials due to their unique physicochemical properties and the diverse interactions they can engage in. In the field of supramolecular polymerization, however, halogen effects remain poorly understood, and investigations have been restricted to halogen bonding or the inclusion of polyfluorinated side groups. Recent contributions from our group have revealed that chlorine ligands greatly influence molecular packing and pathway complexity phenomena of various metal complexes. These results prompted us to explore the role of the halogen nature on supramolecular polymerization, a phenomenon that has remained unexplored to date. To address this issue, we have designed a series of archetypal bispyridyldihalogen Pt II complexes bearing chlorine ( 1 ), bromine ( 2 ), or iodine ( 3 ) and systematically compared their supramolecular polymerization in nonpolar media using various experimental methods and theory. Our studies reveal a remarkably different supramolecular polymerization for the three compounds, which can undergo two competing pathways with either slipped (kinetic) or parallel (thermodynamic) molecular packing. The halogen exerts an inverse effect on the energetic levels of the two self-assembled states, resulting in a single thermodynamic pathway for 3 , a transient kinetic species for 2 , and a hidden thermodynamic state for 1 . This seesaw-like bias of the energy landscape can be traced back to the involvement of the halogens in weak N-H···X hydrogen-bonding interactions in the kinetic pathway, whereas in the thermodynamic pathway the halogens are not engaged in the stabilizing interaction motif but rather amplify solvophobic effects.

Aim: The aim of this study was to evaluate the effect of non-surgical periodontal therapy on circulating levels of the systemic inflammation-associated biomarkers orosomucoid (ORM), high-sensitivity C-reactive protein (hsCRP), chemerin, and retinol-binding protein 4 (RBP4) in overweight or normal-weight patients with periodontitis at 27.5 months after therapy., Materials and Methods: This exploratory subanalysis includes patients from the ABPARO-trial (ClinicalTrials.gov NCT00707369). The per-protocol collective provided untreated periodontitis patients with high (≥28 kg/m 2 ) or moderate (21-24 kg/m 2 ) BMI. Out of the per-protocol collective, 80 patients were randomly selected and stratified for BMI group, sex, and treatment group (antibiotics/placebo), resulting in 40 overweight and normal-weight patients. Patients received non-surgical periodontal therapy and maintenance at 3-month intervals. Plasma samples from baseline and 27.5 months following initial treatment were used to measure the concentrations of ORM, hsCRP, chemerin, and RBP4., Results: At the 27.5-month examination, ORM and hsCRP decreased noticeably in the overweight group (ORM: p = .001, hsCRP: p = .004) and normal-weight patients (ORM: p = .007, hsCRP: p < .001). Chemerin decreased in the overweight group (p = .048), and RBP4 concentrations remained stable., Conclusion: Non-surgical periodontal therapy reduced systemically elevated inflammation-associated biomarkers in periodontitis patients. These improvements were more pronounced in overweight patients than in normal-weight patients., (© 2020 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

In recent years, the development of sophisticated analytical tools, kinetic models and sample preparation methods has significantly advanced the field of supramolecular polymerization, where the competition of kinetic vs. thermodynamic processes has become commonplace for a wide range of building blocks. Typically, the kinetic pathways are identified in thermally controlled assembly experiments before they ultimately evolve to the thermodynamic minimum. However, there might be cases where the identification and thus the assessment of the influence of kinetic aggregates is not trivial, making the analysis of the self-assembly processes a hard task. Herein, we demonstrate that "hidden" kinetic pathways can have drastic consequences on supramolecular polymerization processes, to the point that they can even overrule thermodynamic implications. To this end, we analyzed in detail the supramolecular polymerization of a chiral Pd II complex 1 that forms two competing aggregates ( Agg I and Agg II ) of which kinetic Agg II is formed through a "hidden" pathway, i.e. this pathway is not accessible by common thermal polymerization protocols. The hidden pathway exhibits two consecutive steps: first, Agg II is formed in a cooperative process, which subsequently evolves to clustered superstructures driven by rapid kinetics. At standard conditions, Agg II displays an extraordinary kinetic stability (>6 months), which could be correlated to its cooperative mechanism suppressing nucleation of thermodynamic Agg I . Furthermore, the fast kinetics of cluster formation sequester monomers from the equilibria in solution and prevents the system from relaxing into the thermodynamic minimum, thus highlighting the key implications of hidden pathways in governing supramolecular polymerization processes., (This journal is © The Royal Society of Chemistry 2020.)

The aim of this follow-up study was, to compare the effects of mechanical periodontal therapy with or without adjunctive amoxicillin and metronidazole on the subgingival microbiome of smokers with periodontitis using 16S rDNA amplicon next generation sequencing. Fifty-four periodontitis patients that smoke received either non-surgical periodontal therapy with adjunctive amoxicillin and metronidazole (n = 27) or with placebos (n = 27). Subgingival plaque samples were taken before and two months after therapy. Bacterial genomic DNA was isolated and the V4 hypervariable region of the bacterial 16S rRNA genes was amplified. Up to 96 libraries were normalized and pooled for Illumina MiSeq paired-end sequencing with almost fully overlapping 250 base pairs reads. Exact ribosomal sequence variants (RSVs) were inferred with DADA2. Microbial diversity and changes on the genus and RSV level were analyzed with non-parametric tests and a negative binomial regression model, respectively. Before therapy, the demographic, clinical, and microbial parameters were not significantly different between the placebo and antibiotic groups. Two months after the therapy, clinical parameters improved and there was a significantly increased dissimilarity of microbiomes between the two groups. In the antibiotic group, there was a significant reduction of genera classified as Porphyromonas, Tannerella , and Treponema , and 22 other genera also decreased significantly, while Selenomonas, Capnocytophaga, Actinomycetes , and five other genera significantly increased. In the placebo group, however, there was not a significant decrease in periodontal pathogens after therapy and only five other genera decreased, while Veillonella and nine other genera increased. We conclude that in periodontitis patients who smoke, microbial shifts occurred two months after periodontal therapy with either antibiotics or placebo, but genera including periodontal pathogens decreased significantly only with adjunctive antibiotics., (Copyright © 2020 Hagenfeld, Matern, Prior, Harks, Eickholz, Lorenz, Kim, Kocher, Meyle, Kaner, Schlagenhauf, Harmsen and Ehmke.)

Pathway complexity, hierarchical organization, out of equilibrium, and metastable or kinetically trapped species are common terms widely used in recent, high-quality publications in the field of supramolecular polymers. Often, the terminologies used to describe the different self-assembly pathways, the species involved, as well as their relationship and relative stability are not trivial. Different terms and classifications are commonly found in the literature, however, in many cases, without clear definitions or guidelines on how to use them and how to determine them experimentally. The aim of this Minireview is to classify, differentiate, and correlate the existing concepts with the help of recent literature reports to provide the reader with a general insight into thermodynamic and kinetic aspects of complex supramolecular polymerization processes. A good comprehension of these terms and concepts should contribute to the development of new complex, functional materials., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Statistical copolymerization plays a key role in many biological and technological processes; however, mechanistic understanding of the formation of analogous supramolecular counterparts remains limited. Herein, we report detailed insights into the supramolecular co-assembly of two π-conjugated Pd II and Pt II complexes, which in isolation self-assemble into flexible fibers and nanodisks, respectively. An efficient single-step co-assembly into only one type of nanostructure (fibers or nanodisks) takes place if any of the components is in excess. In contrast, equimolar mixtures lead to Pd II -rich fiber-like co-assemblies by a statistical co-nucleation event along with a residual amount of self-sorted nanodisks in a stepwise manner., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

To diagnose von Willebrand disease (vWD) and to monitor drug efficacy, several tests have been established that are not, however, focused on the platelet adhesion properties of von Willebrand factor (vWF). The new platelet retention test Homburg (RTH) is characterized by a nonthrombogenic filter that retains platelets from blood when it is pressed through this filter. It was the aim of this study to examine the capability of this test to monitor the adhesive properties of vWF after its substitution in vWD or its release by desmopressin infusion. The RTH demonstrated a striking sensitivity for vWF after its release from endogenous storage sites or its supplementation in vivo as well as in vitro, whereas it did not detect an inhibition of platelet aggregability due to aspirin. Desmopressin infusions led to an immediate and highly significant increase of RTH platelet retention, followed by a gradual decline to initial values during the next 4 hours. The transfusion of a vWF concentrate also resulted in RTH data that demonstrated different kinetics than established parameters such as vWF:antigen, vWF:RiCoF, or the PFA-100 in vitro bleeding analysis. Additional in vitro experiments confirmed the correlation of RTH values with vWF concentrations. In conclusion, the RTH may be efficient to complement presently used measures to monitor vWD therapy with desmopressin or vWF concentrates.