Solvent constraints for biopolymer folding and evolution in extraterrestrial environments.

We propose that spontaneous folding and molecular evolution of biopolymers are two universal aspects that must concur for life to happen. These aspects are fundamentally related to the chemical composition of biopolymers and crucially depend on the solvent in which they are embedded. We show that molecular information theory and energy landscape theory allow us to explore the limits that solvents impose on biopolymer existence. We consider 54 solvents, including water, alcohols, hydrocarbons, halogenated solvents, aromatic solvents, and low molecular weight substances made up of elements abundant in the universe, which may potentially take part in alternative biochemistries. We find that along with water, there are many solvents for which the liquid regime is compatible with biopolymer folding and evolution. We present a ranking of the solvents in terms of biopolymer compatibility. Many of these solvents have been found in molecular clouds or may be expected to occur in extrasolar planets.

The distinct cell physiology of Bradyrhizobium at the population and cellular level.

The α-Proteobacteria belonging to Bradyrhizobium genus are microorganisms of extreme slow growth. Despite their extended use as inoculants in soybean production, their physiology remains poorly characterized. In this work, we produced quantitative data on four different isolates: B. diazoefficens USDA110, B. diazoefficiens USDA122, B. japonicum E109 and B. japonicum USDA6 which are representative of specific genomic profiles. Notably, we found conserved physiological traits conserved in all the studied isolates: (i) the lag and initial exponential growth phases display cell aggregation; (ii) the increase in specific nutrient concentration such as yeast extract and gluconate hinders growth; (iii) cell size does not correlate with culture age; and (iv) cell cycle presents polar growth. Meanwhile, fitness, cell size and in vitro growth widely vary across isolates correlating to ribosomal RNA operon number. In summary, this study provides novel empirical data that enriches the comprehension of the Bradyrhizobium (slow) growth dynamics and cell cycle.

Associating protein sequence positions with the modulation of quantitative phenotypes.

Although protein sequences encode the information for folding and function, understanding their link is not an easy task. Unluckily, the prediction of how specific amino acids contribute to these features is still considerably impaired. Here, we developed a simple algorithm that finds positions in a protein sequence with potential to modulate the studied quantitative phenotypes. From a few hundred protein sequences, we perform multiple sequence alignments, obtain the per-position pairwise differences for both the sequence and the observed phenotypes, and calculate the correlation between these last two quantities. We tested our methodology with four cases: archaeal Adenylate Kinases and the organisms optimal growth temperatures, microbial rhodopsins and their maximal absorption wavelengths, mammalian myoglobins and their muscular concentration, and inhibition of HIV protease clinical isolates by two different molecules. We found from 3 to 10 positions tightly associated with those phenotypes, depending on the studied case. We showed that these correlations appear using individual positions but an improvement is achieved when the most correlated positions are jointly analyzed. Noteworthy, we performed phenotype predictions using a simple linear model that links per-position divergences and differences in the observed phenotypes. Predictions are comparable to the state-of-art methodologies which, in most of the cases, are far more complex. All of the calculations are obtained at a very low information cost since the only input needed is a multiple sequence alignment of protein sequences with their associated quantitative phenotypes. The diversity of the explored systems makes our work a valuable tool to find sequence determinants of biological activity modulation and to predict various functional features for uncharacterized members of a protein family.

Treatment of peri-implantitis with a flapless surgical access combined with implant surface decontamination and adjunctive systemic antibiotics: A retrospective case series study.

AIM: To evaluate the effectiveness of a flapless surgical approach in the treatment of peri-implantitis and to explore the factors influencing its outcome. MATERIALS AND METHODS: The present retrospective study evaluated patients with at least one implant diagnosed with peri-implantitis and treated with a flapless surgical access, with or without systemic antimicrobials, curettage and, when needed, prostheses modification. Clinical and radiographic parameters were assessed at baseline and at 3 months and at least 12 months. The primary outcome was disease resolution (≤1 bleeding sites, probing depth [PD] ≤5 mm, no bone loss >0.5 mm). Multilevel regression analyses were used to identify predictors influencing the probability of attaining disease resolution. RESULTS: One hundred and seventeen patients with 338 implants were included. Disease resolution was attained in 54.4% of the 338 implants receiving flapless surgical access. At the end of the follow-up period, 111 patients (94.9%) with 295 implants (87.3%) did not require any further treatment, with 81.4% of these implants presenting PD ≤ 5 mm. History of periodontitis and PD at baseline were identified as negative predictors, while compliance with supportive peri-implant care, a machined surface and the adjunctive use of systemic azithromycin or metronidazole were identified as positive predictive factors for disease resolution. CONCLUSIONS: A flapless surgical approach led to disease resolution in 54.4% of the implants with peri-implantitis. Several risk/protective predictors for disease resolution were identified.

The effect of one-time abutment placement on clinical and radiographic outcomes: A 5-year randomized clinical trial.

OBJECTIVE: The aim of this study was to evaluate the long-term (5 years) clinical efficacy of the one-abutment one-time protocol (test) versus the standard of care by placing the definitive abutment on the day of the prosthetic delivery (control). MATERIALS AND METHODS: In this study, 39 subjects with 60 implants were randomly allocated to either the test or the control group. Changes in the radiographic interproximal bone levels (DIB), modified sulcus bleeding index, probing depth, modified plaque index, papilla fill (Jemt score), incidence of peri-implantitis and peri-implant mucositis as well as patient-reported outcomes measures (PROMs) were collected and compared at 1, 3 and 5 years. RESULTS: At 5 years, the control group showed a greater, although not statistically significant, change in mean DIB values (0.97 mm vs. 0.53 mm). Regarding the other clinical parameters evaluated, no statistically significant differences were observed between groups at any time point. At 5 years, 51% of the implants presented peri-implant mucositis (25.5% in the control and 23.5% in the test), and only one implant in the test group developed peri-implantitis. CONCLUSIONS: The connection and disconnection of healing abutments during the healing period was not associated with higher long-term bone loss. Clinical outcomes and PROMs were similar between groups.

The evolving copiotrophic/oligotrophic dichotomy: From Winogradsky to physiology and genomics.

Nearly 100 years ago, Winogradsky published a classic communication in which he described two groups of microbes, zymogenic and autochthonous. When organic matter penetrates the soil, zymogenic microbes quickly multiply and degrade it, then giving way to the slow combustion of autochthonous microbes. Although the text was originally written in French, it is often cited by English-speaking authors. We undertook a complete translation of the 1924 publication, which we provide as Supporting information. Here, we introduce the translation and describe how the zymogenic/autochthonous dichotomy shaped research questions in the study of microbial diversity and physiology. We also identify in the literature three additional and closely related dichotomies, which we propose to call exclusive copiotrophs/oligotrophs, coexisting copiotrophs/oligotrophs and fast-growing/slow-growing microbes. While Winogradsky focussed on a successional view of microbial populations over time, the current discussion is focussed on the differences in the specific growth rate of microbes as a function of the concentration of a given limiting substrate. In the future, it will be relevant to keep in mind both nutrient-focussed and time-focussed microbial dichotomies and to design experiments with both isolated laboratory cultures and multi-species communities in the spirit of Winogradsky's direct method.

Ecology theory disentangles microbial dichotomies.

Microbes are often discussed in terms of dichotomies such as copiotrophic/oligotrophic and fast/slow-growing microbes, defined using the characterisation of microbial growth in isolated cultures. The dichotomies are usually qualitative and/or study-specific, sometimes precluding clear-cut results interpretation. We can unravel microbial dichotomies as life history strategies by combining ecology theory with Monod curves, a laboratory mathematical tool of bacterial physiology that relates the specific growth rate of a microbe with the concentration of a limiting nutrient. Fitting of Monod curves provides quantities that directly correspond to key parameters in ecological theories addressing species coexistence and diversity, such as r/K selection theory, resource competition and community structure theory and the CSR triangle of life strategies. The resulting model allows us to reconcile the copiotrophic/oligotrophic and fast/slow-growing dichotomies as different subsamples of a life history strategy triangle that also includes r/K strategists. We also used the number of known carbon sources together with community structure theory to partially explain the diversity of heterotrophic microbes observed in metagenomics experiments. In sum, we propose a theoretical framework for the study of natural microbial communities that unifies several existing proposals. Its application would require the integration of metagenomics, metametabolomics, Monod curves and carbon source data.

r/K selection of GC content in prokaryotes.

The guanine/cytosine (GC) content of prokaryotic genomes is species-specific, taking values from 16% to 77%. This diversity of selection for GC content remains contentious. We analyse the correlations between GC content and a range of phenotypic and genotypic data in thousands of prokaryotes. GC content integrates well with these traits into r/K selection theory when phenotypic plasticity is considered. High GC-content prokaryotes are r-strategists with cheaper descendants thanks to a lower average amino acid metabolic cost, colonize unstable environments thanks to flagella and a bacillus form and are generalists in terms of resource opportunism and their defence mechanisms. Low GC content prokaryotes are K-strategists specialized for stable environments that maintain homeostasis via a high-cost outer cell membrane and endospore formation as a response to nutrient deprivation, and attain a higher nutrient-to-biomass yield. The lower proteome cost of high GC content prokaryotes is driven by the association between GC-rich codons and cheaper amino acids in the genetic code, while the correlation between GC content and genome size may be partly due to functional diversity driven by r/K selection. In all, molecular diversity in the GC content of prokaryotes may be a consequence of ecological r/K selection.

Complications and treatment errors in peri-implant hard tissue management.

Bone augmentation procedures aim to regenerate the deficient alveolar ridge to properly place dental implants that are completely surrounded by bone. However, these are invasive and technically demanding surgeries that are not free of either complications or treatment errors. Careful patient selection and preparation is a mandatory process to reduce the rate of complications in bone regeneration procedures, irrespective of the technique used. It is important to assess the cost benefit of the intervention and to evaluate the potential impact on the patient's quality of life, especially in the elderly and medically compromised patients. Most common postoperative complications are wound dehiscences, which may be reduced, at least partially, by proper knowledge of the surgical technique and the craniofacial anatomy. Other complications that may appear are postoperative infections or nerve injuries. The aim of this narrative review is to summarize the best available scientific evidence on the incidence of complications, as well as the ideal strategies for their prevention and management. Depending on the severity of the complication, treatment approaches may vary and can include drug prescription or even surgical re-entries to remove exposed barrier membranes or contaminated bone grafts. Adequate prevention and proper management of complications associated with bone augmentation interventions are a requirement for clinicians carrying out these demanding procedures. A series of cases illustrating proper management of complications in different clinical scenarios is presented.

Minimal invasiveness in vertical ridge augmentation.

Vertical ridge augmentation is one of the most challenging procedures in implant dentistry because of the advanced skills required by the operator and the fact that bone augmentation is aimed outside the bony contour, in an environment of reduced blood supply. What is more, the flap management required to ensure soft tissue closure frequently leads to associated comorbidities in terms of swelling and hematomas. For these reasons, and even if autologous onlay block grafts are still the gold standard, new techniques and biomaterials have favored the development of potentially less invasive approaches. The present work evaluates the most recent strategies in vertical ridge augmentation to reduce invasiveness and complications, including diagnostic/treatment planning considerations, surgical techniques, digital tools (eg, customized titanium meshes/membranes or bone blocks), and future trends in the field of tissue engineering and cell therapy.

Structure-Based Optimization of Carbendazim-Derived Tubulin Polymerization Inhibitors through Alchemical Free Energy Calculations.

Carbendazim derivatives, commonly used as antiparasitic drugs, have shown potential as anticancer agents due to their ability to induce cell cycle arrest and apoptosis in human cancer cells by inhibiting tubulin polymerization. Crystallographic structures of α/ß-tubulin multimers complexed with nocodazole and mebendazole, two carbendazim derivatives with potent anticancer activity, highlighted the possibility of designing compounds that occupy both benzimidazole- and colchicine-binding sites. In addition, previous studies have demonstrated that the incorporation of a phenoxy group at position 5/6 of carbendazim increases the antiproliferative activity in cancer cell lines. Despite the significant progress made in identifying new tubulin-targeting anticancer compounds, further modifications are needed to enhance their potency and safety. In this study, we explored the impact of modifying the phenoxy substitution pattern on antiproliferative activity. Alchemical free energy calculations were used to predict the binding free energy difference upon ligand modification and define the most viable path for structure optimization. Based on these calculations, seven compounds were synthesized and evaluated against lung and colon cancer cell lines. Our results showed that compound 5a, which incorporates an α-naphthyloxy substitution, exhibits the highest antiproliferative activity against both cancer lines (SK-LU-1 and SW620, IC50 < 100 nM) and induces morphological changes in the cells associated with mitotic arrest and mitotic catastrophe. Nevertheless, the tubulin polymerization assay showed that 5a has a lower inhibitory potency than nocodazole. Molecular dynamics simulations suggested that this low antitubulin activity could be associated with the loss of the key H-bond interaction with V236. This study provides insights into the design of novel carbendazim derivatives with anticancer activity.

NGOME-Lite: Proteome-wide prediction of spontaneous protein deamidation highlights differences between taxa.

Asparagines in proteins deamidate spontaneously, which changes the chemical structure of a protein and often affects its function. Current prediction algorithms for asparagine deamidation require a structure as an input or are too slow to be applied at a proteomic scale. We present NGOME-Lite, a new version of our sequence-based predictor for spontaneous asparagine deamidation that is faster by over two orders of magnitude at a similar degree of accuracy. The algorithm takes into account intrinsic sequence propensities and slowing down of deamidation by local structure. NGOME-Lite can run in a proteomic analysis mode that provides the half-time of the intact form of each protein, predicted by taking into account sequence propensities and structural protection or sequence propensities only, and a structure protection factor. The detailed analysis mode also provides graphical output for all Asn residues in the query sequence. We applied NGOME-Lite to over 257,000 sequences in 38 proteomes and found that different taxa differ in their predicted deamidation dynamics. Spontaneous protein deamidation is faster in Eukarya than in Bacteria because of a higher degree of structural protection in the latter. Predicted protein deamidation half-lifes correlate with protein turnover in human, mouse, rat, C. elegans and budding yeast but not in two plants and two bacteria. NGOME-Lite is implemented in a docker container available at https://ngome.proteinphysiologylab.org.

Efficacy of adjunctive measures in the non-surgical treatment of peri-implantitis: A systematic review.

AIM: The aim of this systematic review was to evaluate the efficacy of patient-performed or administered adjunctive measures to non-surgical peri-implantitis therapy in terms of probing depth (PD) and/or bleeding on probing (BoP) reductions. MATERIALS AND METHODS: Randomized and controlled clinical trials with at least 6 months of follow-up were searched in three databases. Secondary outcomes included implant loss, disease resolution, recurrence of peri-implantitis, need of re-treatment, changes in marginal bone levels, patient-reported outcomes and adverse effects. RESULTS: Of 567 titles, 10 publications, reporting 9 investigations, were included. Three types of adjunctive measures were found (local/systemic antimicrobials and probiotics). Four studies evaluated the effects of local antimicrobials (i.e., minocycline microspheres, chlorhexidine chips or a metronidazole + amoxicillin gel), three studies evaluated systemic antimicrobials (either amoxicillin + metronidazole or metronidazole alone) and two studies evaluated probiotics (Lactobacillus reuteri strains). The addition of local antimicrobials led to modest improvements in PD reduction. Systemic antimicrobials showed significantly greater reductions in PD and BoP, especially at initially deep sites (PD > 6 mm). Due to the large heterogeneity among included studies, no meta-analyses were performed. CONCLUSIONS: Different adjunctive measures in the non-surgical treatment of peri-implantitis have different impact in terms of PD and BoP reductions. Improved PD reductions result after the use of systemic antimicrobials, and to a lesser extent, after the use of local antimicrobials.

Bone preservation or augmentation simultaneous with or prior to dental implant placement: A systematic review of outcomes and outcome measures used in clinical trials in the last 10 years.

AIM: To evaluate outcome measures and methods of assessment in clinical studies on bone augmentation/preservation procedures for the placement of dental implants. MATERIALS AND METHODS: A systematic search was performed on three databases from January 2011 to April 2021 to identify clinical studies reporting on any type of bone augmentation/preservation procedure. The outcomes that have been used to assess efficacy or performance in each study were registered and assigned to different domains (group of outcomes). The review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. RESULTS: Seven-hundred and eighty-three publications were included. Only 81.8% of the papers had a clear definition of their primary outcome. The rate of complications (59.3%), implant survival (58.2%), 3D radiographic bone gain/change (30%), marginal bone level (MBL; 29%), and histological outcomes (25.5%) were the most frequently reported outcome domains. The most commonly used primary outcome was 3D radiographic bone gain/change (25.8%), followed by implant survival (13.0%). Patient-reported outcome measures (PROMs) were reported in 15.7% of studies. Differences in the reported outcomes were observed among different types of bone preservation/augmentation interventions (i.e., alveolar ridge preservation, immediate implants, horizontal and/or vertical ridge augmentation, and sinus floor augmentation). CONCLUSION: Within the past decade, great heterogeneity was observed among the outcomes considered in studies evaluating bone preservation/augmentation procedures. Three-dimensional radiographic bone gain/change was the most routinely reported main outcome variable, while PROMs were rarely reported.

Relevant domains, core outcome sets and measurements for implant dentistry clinical trials: The Implant Dentistry Core Outcome Set and Measurement (ID-COSM) international consensus report.

AIM: Lack of consistently reported outcomes limits progress in evidence-based implant dentistry and quality of care. The objective of this initiative was to develop a core outcome set (COS) and measurements for implant dentistry clinical trials (ID-COSM). MATERIALS AND METHODS: This Core Outcome Measures in Effectiveness Trials (COMET)-registered international initiative comprised six steps over 24 months: (i) systematic reviews of outcomes reported in the last 10 years; (ii) international patient focus groups; (iii) a Delphi project with a broad range of stakeholders (care providers, clinical researchers, methodologists, patients and industry representatives); (iv) expert group discussions organizing the outcomes in domains using a theoretical framework and identifying the COSs; (v) identification of valid measurement systems to capture the different domains and (vi) final consensus and formal approval involving experts and patients. The methods were modified from the best practice approach following the Outcome Measures in Rheumatoid Arthritis Clinical Trial and COMET manuals. RESULTS: The systematic reviews and patient focus groups identified 754 (665 + 89, respectively) relevant outcome measures. After elimination of redundancies and duplicates, 111 were formally assessed in the Delphi project. By applying pre-specified filters, the Delphi process identified 22 essential outcomes. These were reduced to 13 after aggregating alternative assessments of the same features. The expert committee organized them into four core outcome areas: (i) pathophysiology, (ii) implant/prosthesis lifespan, (iii) life impact and (iv) access to care. In each area, core outcomes were identified to capture both the benefits and harms of therapy. Mandatory outcome domains included assessment of surgical morbidity and complications, peri-implant tissue health status, intervention-related adverse events, complication-free survival and overall patient satisfaction and comfort. Outcomes deemed mandatory in specific circumstances comprised function (mastication, speech, aesthetics and denture retention), quality of life, effort for treatment and maintenance and cost effectiveness. Specialized COSs were identified for bone and soft-tissue augmentation procedures. The validity of measurement instruments ranged from international consensus (peri-implant tissue health status) to early identification of important outcomes (patient-reported outcomes identified by the focus groups). CONCLUSIONS: The ID-COSM initiative reached a consensus on a core set of mandatory outcomes for clinical trials in implant dentistry and/or soft tissue/bone augmentation. Adoption in future protocols and reporting on the respective domain areas by currently ongoing trials will contribute to improving evidence-informed implant dentistry and quality of care.

Biofilm formation on dental implants with a hybrid surface microtopography: An in vitro study in a validated multispecies dynamic biofilm model.

OBJECTIVES: The objective of this study is to qualitatively and quantitatively evaluate biofilm formation on hybrid titanium implants (HS), with moderately rough and turned surface topographies. MATERIALS AND METHODS: A validated dynamic in vitro multispecies biofilm model, based on bacterial growth under flow and shear conditions resembling the oral cavity, was used to evaluate biofilm formation on the tested implant surfaces. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to compare the biofilm structure and microbial biomass deposited on either the moderately rough or the turned surface of HS. Quantitative polymerase chain reaction (qPCR) was used to evaluate the total bacterial counts and counts of each specific bacterium in biofilms formed on implants with either the moderately rough or the turned surfaces, as in the hybrid titanium implants, after 24, 48 and 72 h. A general linear model was applied to compare the CLSM and qPCR results between the tested implant surfaces. RESULTS: A significantly higher bacterial biomass grew on the moderately rough implant surfaces, compared to the turned surface area of HS implants (p < .05), at all incubation times, as evidenced with both CLSM and SEM. qPCR analysis also demonstrated an important increase in the total and specific bacterial counts in moderately rough surface implants at the three incubation times. CONCLUSIONS: Implant surface topography (moderately rough versus turned) significantly influenced in vitro biofilm formation in terms of biofilm structure, bacterial biomass and quantity of the specific species selected for the model used.

Bone preservation or augmentation simultaneous with or prior to dental implant placement: A systematic review of outcomes and outcome measures used in clinical trials in the last 10 years.

AIM: To evaluate outcome measures and methods of assessment in clinical studies on bone augmentation/preservation procedures for the placement of dental implants. MATERIALS AND METHODS: A systematic search was performed on three databases from January 2011 to April 2021 to identify clinical studies reporting on any type of bone augmentation/preservation procedure. The outcomes that have been used to assess efficacy or performance in each study were registered and assigned to different domains (group of outcomes). The review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. RESULTS: Seven-hundred and eighty-three publications were included. Only 81.8% of the papers had a clear definition of their primary outcome. The rate of complications (59.3%), implant survival (58.2%), 3D radiographic bone gain/change (30%), marginal bone level (MBL; 29%), and histological outcomes (25.5%) were the most frequently reported outcome domains. The most commonly used primary outcome was 3D radiographic bone gain/change (25.8%), followed by implant survival (13.0%). Patient-reported outcome measures (PROMs) were reported in 15.7% of studies. Differences in the reported outcomes were observed among different types of bone preservation/augmentation interventions (i.e., alveolar ridge preservation, immediate implants, horizontal and/or vertical ridge augmentation, and sinus floor augmentation). CONCLUSION: Within the past decade, great heterogeneity was observed among the outcomes considered in studies evaluating bone preservation/augmentation procedures. Three-dimensional radiographic bone gain/change was the most routinely reported main outcome variable, while PROMs were rarely reported.

Clinical, microbiological and biochemical impact of a supportive care protocol with an air-polishing device, after surgical treatment of peri-implantitis: Randomized clinical trial.

OBJECTIVES: The aim of the present study was to evaluate the efficacy of a supportive peri-implant care (SPIC) protocol after surgical therapy of peri-implantitis, combining ultrasonic mechanical debridement and glycine powder air polishing. MATERIALS AND METHODS: Thirty subjects diagnosed with peri-implantitis and treated by means of access flap were randomized 6 months later into two different SPIC groups: the test group combined a piezoelectric ultrasonic instrumentation with a specific implant PEEK tip and glycine powder air polishing, while control group received the same ultrasonic instrumentation together with a rubber cup and a polishing paste. Patients were followed for 12 months, with intermediate SPIC visits every 3 months. Clinical, radiological, microbiological and biochemical outcome variables were registered and calculated. RESULTS: After 12 months of SPIC, probing depths (PD) showed a mean reduction of 0.33 ± 0.11 mm, with significant differences (p < .001) between the test (-0.84 ± 0.43 mm) and the control group (+0.18 ± 0.73 mm). Healthy peri-implant tissues defined by PD <5 mm, absence of BoP (or in only one site around the implant), and no additional bone loss (<0.5 mm), were observed at the final visit in 83% of the implants (87% in the test group and 80% in the control group, p = .255). No adverse events were reported by the subjects participating in the study. CONCLUSIONS: The SPIC protocol including mechanical ultrasonic debridement and glycine powder air-polishing demonstrated significantly better efficacy in terms of PD reductions. A strict SPIC protocol can maintain for 1 year, or even improve, the results obtained after surgical treatment of peri-implantitis.

Relevant domains, core outcome sets and measurements for implant dentistry clinical trials: The Implant Dentistry Core Outcome Set and Measurement (ID-COSM) international consensus report.

AIM: Lack of consistently reported outcomes limits progress in evidence-based implant dentistry and quality of care. The objective of this initiative was to develop a core outcome set (COS) and measurements for implant dentistry clinical trials (ID-COSM). MATERIALS AND METHODS: This Core Outcome Measures in Effectiveness Trials (COMET)-registered international initiative comprised six steps over 24 months: (i) systematic reviews of outcomes reported in the last 10 years; (ii) international patient focus groups; (iii) a Delphi project with a broad range of stakeholders (care providers, clinical researchers, methodologists, patients and industry representatives); (iv) expert group discussions organizing the outcomes in domains using a theoretical framework and identifying the COSs; (v) identification of valid measurement systems to capture the different domains and (vi) final consensus and formal approval involving experts and patients. The methods were modified from the best practice approach following the Outcome Measures in Rheumatoid Arthritis Clinical Trial and COMET manuals. RESULTS: The systematic reviews and patient focus groups identified 754 (665 + 89, respectively) relevant outcome measures. After elimination of redundancies and duplicates, 111 were formally assessed in the Delphi project. By applying pre-specified filters, the Delphi process identified 22 essential outcomes. These were reduced to 13 after aggregating alternative assessments of the same features. The expert committee organized them into four core outcome areas: (i) pathophysiology, (ii) implant/prosthesis lifespan, (iii) life impact and (iv) access to care. In each area, core outcomes were identified to capture both the benefits and harms of therapy. Mandatory outcome domains included assessment of surgical morbidity and complications, peri-implant tissue health status, intervention-related adverse events, complication-free survival and overall patient satisfaction and comfort. Outcomes deemed mandatory in specific circumstances comprised function (mastication, speech, aesthetics and denture retention), quality of life, effort for treatment and maintenance and cost effectiveness. Specialized COSs were identified for bone and soft-tissue augmentation procedures. The validity of measurement instruments ranged from international consensus (peri-implant tissue health status) to early identification of important outcomes (patient-reported outcomes identified by the focus groups). CONCLUSIONS: The ID-COSM initiative reached a consensus on a core set of mandatory outcomes for clinical trials in implant dentistry and/or soft tissue/bone augmentation. Adoption in future protocols and reporting on the respective domain areas by currently ongoing trials will contribute to improving evidence-informed implant dentistry and quality of care.

Clinical and microbiological efficacy of indocyanine green-based antimicrobial photodynamic therapy as an adjunct to non-surgical treatment of periodontitis: a randomized controlled clinical trial.

OBJECTIVES: The aim of the present randomized clinical trial (RCT) with a parallel arm design was to evaluate the clinical and microbiological efficacy of repeated ICG-aPDT as an adjunct to full-mouth subgingival debridement in the treatment of periodontitis. MATERIALS AND METHODS: Twenty-four periodontitis patients were treated with full-mouth ultrasonic subgingival debridement (FMUD). Initial sites with probing depth (PD) > 4 mm were randomly assigned to receive the test (ICG-aPDT with an 810 nm diode laser) or the control treatment (off-mode aPDT) one and four weeks after FMUD. Clinical parameters were registered after 3 and 6 months. The presence of the main periodontal pathogens in subgingival samples was assessed with real-time PCR. RESULTS: Both treatment modalities resulted in significant clinical improvements at 3 and 6 months. The only significant differences in favour of the test group were found at 6 months for a higher PD reduction in initial deep pockets (PD ≥ 6 mm) and a higher percentage of closed pockets (PD ≤ 4 mm/no bleeding on probing). Limited microbiological changes were observed in both groups after treatment with no inter-group difference, except for a more significant reduction in Aggregatibacter actinomycetemcomitans and Parvimonas micra levels in the test group at 3 months. CONCLUSION: The combination of repeated ICG-aPDT and FMUD provided no benefits except for selective clinical and microbiological improvements compared to FMUD alone. CLINICAL RELEVANCE: Based on the obtained results, only limited adjunctive effects could be found for the combined use of ICG-aPDT and FMUD. Further, well-designed RCT with larger sample sizes are required to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04671394.