Piperazine-derived small molecules as potential Flaviviridae NS3 protease inhibitors. In vitro antiviral activity evaluation against Zika and Dengue viruses.

Since 2011 Direct Acting antivirals (DAAs) drugs targeting different non-structural (NS) viral proteins (NS3, NS5A or NS5B inhibitors) have been approved for clinical use in HCV therapies. However, currently there are not licensed therapeutics to treat Flavivirus infections and the only licensed DENV vaccine, Dengvaxia, is restricted to patients with preexisting DENV immunity. Similarly to NS5 polymerase, the NS3 catalytic region is evolutionarily conserved among the Flaviviridae family sharing strong structural similarity with other proteases belonging to this family and therefore is an attractive target for the development of pan-flavivirus therapeutics. In this work we present a library of 34 piperazine-derived small molecules as potential Flaviviridae NS3 protease inhibitors. The library was developed through a privileged structures-based design and then biologically screened using a live virus phenotypic assay to determine the half-maximal inhibitor concentration (IC50) of each compound against ZIKV and DENV. Two lead compounds, 42 and 44, with promising broad-spectrum activity against ZIKV (IC50 6.6 µM and 1.9 µM respectively) and DENV (IC50 6.7 µM and 1.4 µM respectively) and a good security profile were identified. Besides, molecular docking calculations were performed to provide insights about key interactions with residues in NS3 proteases' active sites.

Rehabilitation of full-arch edentulism with fixed or removable dentures retained by root-form dental implants: A systematic review of outcomes and outcome measures used in clinical research in the last 10 years.

AIM: To evaluate outcome measures, methods of assessment, and analysis in clinical studies on the rehabilitation of full-arch edentulism with implant-supported fixed or removable prostheses. MATERIALS AND METHODS: A protocol-oriented search was conducted in MEDLINE via PubMed, EMBASE, and Cochrane Library (PROSPERO registration CRD42021265179) from 1 January 2011 to 27 July 2021 to identify longitudinal studies reporting on the rehabilitation of edentulous patients with implant-supported prostheses. The primary aim of this study was the collection of all objectively reported outcomes in each study. Secondary aims included the description of the methods of assessment and analytical methods. Risk of bias was applied according to the study design (randomized controlled trial, cohort study, or descriptive pre-post study). Individual study data were extracted into an outcomes matrix. Outcomes were grouped into domains and descriptively analysed. A network diagram was generated to establish relationships between domains. The present review follows the PRISMA statement. RESULTS: The screening and selection processes resulted in the identification of 491 publications, corresponding to 421 different studies (cohorts of patients). Only 24% of the studies reported the use of EQUATOR network guidelines. Implant failure/survival was the most reported outcome (270 studies), but the criterion to determine implant failure and/or survival was frequently not described or was ambiguous. Implant success was much less frequently reported (88) and was based on several heterogenous composite definitions. Marginal bone levels (233 studies), technical complications (158), and clinical outcomes (150), including peri-implant soft tissue and implant stability assessment, were also frequently reported. Patient-reported outcome measures (PROMs) (145) and function-based outcomes (40) were predominantly reported in isolation from other outcomes and most frequently in removable restorations. While quality of life was evaluated using valid instruments, patient satisfaction was evaluated based on a common sense concept of satisfaction. Economic outcomes were under-reported (13). CONCLUSIONS: There is great heterogeneity in the criteria to define implant failure or survival and implant success, which prevents the comparison of rates across studies. Even though studies frequently report multiple outcomes, PROMs are usually reported in isolation from other outcomes. It would be valuable to have a set of core outcome variables and standardized methods of measurement for future studies.

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.

Rehabilitation of full-arch edentulism with fixed or removable dentures retained by root-form dental implants: A systematic review of outcomes and outcome measures used in clinical research in the last 10 years.

AIM: To evaluate outcome measures, methods of assessment, and analysis in clinical studies on the rehabilitation of full-arch edentulism with implant-supported fixed or removable prostheses. MATERIALS AND METHODS: A protocol-oriented search was conducted in MEDLINE via PubMed, EMBASE, and Cochrane Library (PROSPERO registration CRD42021265179) from 1 January 2011 to 27 July 2021 to identify longitudinal studies reporting on the rehabilitation of edentulous patients with implant-supported prostheses. The primary aim of this study was the collection of all objectively reported outcomes in each study. Secondary aims included the description of the methods of assessment and analytical methods. Risk of bias was applied according to the study design (randomized controlled trial, cohort study, or descriptive pre-post study). Individual study data were extracted into an outcomes matrix. Outcomes were grouped into domains and descriptively analysed. A network diagram was generated to establish relationships between domains. The present review follows the PRISMA statement. RESULTS: The screening and selection processes resulted in the identification of 491 publications, corresponding to 421 different studies (cohorts of patients). Only 24% of the studies reported the use of EQUATOR network guidelines. Implant failure/survival was the most reported outcome (270 studies), but the criterion to determine implant failure and/or survival was frequently not described or was ambiguous. Implant success was much less frequently reported (88) and was based on several heterogenous composite definitions. Marginal bone levels (233 studies), technical complications (158), and clinical outcomes (150), including peri-implant soft tissue and implant stability assessment, were also frequently reported. Patient-reported outcome measures (PROMs) (145) and function-based outcomes (40) were predominantly reported in isolation from other outcomes and most frequently in removable restorations. While quality of life was evaluated using valid instruments, patient satisfaction was evaluated based on a common sense concept of satisfaction. Economic outcomes were under-reported (13). CONCLUSIONS: There is great heterogeneity in the criteria to define implant failure or survival and implant success, which prevents the comparison of rates across studies. Even though studies frequently report multiple outcomes, PROMs are usually reported in isolation from other outcomes. It would be valuable to have a set of core outcome variables and standardized methods of measurement for future studies.

Scientific rationale for study: Consistent data on the outcomes of treatments for full-arch edentulism are fundamental for establishing high-quality clinical practices with effective impact on patients' lives. Principal findings: Despite the increasing number of studies assessing the rehabilitation of full-arch edentulism with implant-supported prostheses, there has been little adherence to reporting guidelines (EQUATOR network), resulting in high variability regarding the type of outcomes reported. The clinical performance of these restorations has been mostly evaluated using clinician-oriented and patient-reported outcomes. Assessment methods are frequently not described and vary across studies. Practical implications: It would be valuable to have a set of core outcome variables and standardized methods of measurement for future studies.

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 in-situ evaluation of the effect of rubber dam isolation on bond strength to enamel.

OBJECTIVE: To evaluate the effect of rubber dam isolation on shear bond strength of two different adhesive systems to enamel. MATERIALS AND METHODS: The mesial, distal, lingual, and vestibular enamel surfaces of thirty human third molars were prepared (total n = 120). A custom splint was made to fit a volunteer's maxilla, holding the specimens in place in the oral cavity. Four composite resin cylinders were bonded to each tooth with one of two bonding agents (OptiBond FL and Prime&Bond active) with or without rubber dam isolation. Shear bond strength was tested in a universal testing machine and failure modes were assessed. Significance level for statistical analyses was set at 5%. RESULTS: All pairwise comparisons revealed statistical differences (p < 0.05). The highest mean shear bond strength values were obtained in rubber dam experimental groups, regardless of the adhesive system. Group OptiBond FL with rubber dam presented the highest mean bond strength values. Fracture modes for specimens bonded without rubber dam isolation were adhesive and cohesive within enamel, while rubber dam experimental groups revealed only cohesive fractures. CONCLUSIONS: Absolute isolation with rubber dam increases bond strength to enamel, independent of the adhesive system. The three-step total-etch system OptiBond FL provided significantly higher bond strength values than Prime&Bond active under both experimental conditions. CLINICAL SIGNIFICANCE: Rubber dam isolation has a significant effect on bond strengths to enamel, independent of the adhesive system. Its application is, therefore, advised whenever adhesive procedures are performed. A filled three-step etch-and-rinse adhesive performed superiorly, with or without rubber dam isolation, when bonding to enamel compared to an isopropanol-based universal adhesive.

Repurposing Study of 4-Acyl-1-phenylaminocarbonyl-2-substituted-piperazine Derivatives as Potential Anticancer Agents-In Vitro Evaluation against Breast Cancer Cells.

Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity toward cancer cells. Since repurposing approved drugs for cancer therapy has been a successful strategy in recent years, in this study, we screened a library of antiviral piperazine-derived compounds as anticancer agents. The compounds included a piperazine ring and aryl urea functions, which are privileged structures present in several anti-breast cancer drugs. The selective cytotoxic activity of a set of thirty-four 4-acyl-2-substituted piperazine urea derivatives against MCF7 breast cancer cells and MCF 10A normal breast cells was determined. Compounds 31, 32, 35, and 37 showed high selective anticancer activity against breast cancer cells and were also tested against another common type of cancer, non-small cell lung cancer (A549 lung cancer cells versus MRC-5 lung normal cells). Compounds 35 and 37 also showed selectivity against lung cancer cells. These results suggest that compounds 35 and 37 may be promising hit compounds for the development of new anticancer agents.

Luting indirect restorations with resin cements versus composite resins: Effects of preheating and ultrasound energy on film thickness.

OBJECTIVE: This study aims to evaluate and compare the film thickness obtained with a resin cement and two composite resins, preheated and/or ultrasonically vibrated, as luting agents. MATERIALS AND METHODS: One hundred and twenty-six (126) pairs of resin discs were randomly assigned to six experimental groups (n = 21) according to luting agent (Variolink Esthetic LC, IPS Empress Direct or Estelite Omega) and cementation technique (preheating at 68°C and/or ultrasonic vibration). Specimens were luted by applying a controlled force. Following sectioning and film thickness measurement through field emission gun scanning electron microscopy, statistical analysis was carried out considering a 5% significance level. RESULTS: Statistically significant lower film thickness was observed in Variolink Esthetic LC group when compared to all composite resin groups (p < 0.001), except IPS Empress Direct preheated and ultrasonically vibrated group (p = 0.073). IPS Empress Direct with ultrasonic vibration yielded statistically lower film thickness values than Estelite Omega groups, regardless of luting technique (p < 0.05). Ultrasonically vibrated Estelite Omega groups showed statistically lower film thickness values than solely preheated groups (p < 0.05). CONCLUSIONS: Both Variolink Esthetic LC and IPS Empress Direct preheated and ultrasonically vibrated provided the lowest film thickness. The addition of ultrasonic vibration during cementation proved to be effective in reducing film thickness of both tested composite resins. CLINICAL SIGNIFICANCE: The cementation technique will have variable results depending on the luting material. Adhesive cementation protocols with composite resins should mainly consider ultrasonic vibration, but also preheating, as strategies for reducing film thickness. The tested resin cement, alongside with IPS Empress Direct composite resin preheated and ultrasonically vibrated, provided the lowest film thickness among the tested materials and techniques.

Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol.

Nowadays there is not an effective drug for the treatment of infections caused by human adenovirus (HAdV) which supposes a clinical challenge, especially for paediatric and immunosuppressed patients. Here, we describe the design, synthesis and biological evaluation as anti-adenovirus agents of a new library (57 compounds) of diester, monoester and triazole derivatives based on 3-amino-1,2-propanediol skeleton. Seven compounds (17, 20, 26, 34, 44, 60 and 66) were selected based on their high anti-HAdV activity at low micromolar concentration (IC50 from 2.47 to 5.75 µM) and low cytotoxicity (CC50 from 28.70 to >200 µM). In addition, our mechanistic assays revealed that compounds 20 and 44 might be targeting specifically the HAdV DNA replication process, and compound 66 would be targeting HAdV E1A mRNA transcription. For compounds 17, 20, 34 and 60, the mechanism of action seems to be associated with later steps after HAdV DNA replication.

Clinical and radiographic performance of self-locking conical connection implants in the posterior mandible: Five-year results of a two-centre prospective study.

OBJECTIVE: This prospective study aims to assess the 5-year clinical performance of implants with internal conical connection and platform-switched abutments in the posterior mandible. MATERIAL AND METHODS: Healthy adults missing at least two teeth in the posterior mandible and with a natural tooth mesial to the implant site received two or three adjacent implants. After a transmucosal healing period single crown restorations were cemented on platform-switched abutments. Changes in marginal bone levels were investigated in standardized periapical radiographs from surgery and loading (baseline) to 60-months post-loading. RESULTS: Twenty-four patients received 52 implants. Bone remodelling took place between surgery and loading (mean:-0.5, SD:±0.4 mm). From loading to 60 months, there was a mean bone change of 0.27 (SD:±0.47 mm) which stabilized 24 months after prosthesis delivery (mean:0.2, SD:±0.46 mm). 71.7% of all implants presented bone preservation at 60 months irrespective of the initial insertion depth. Two implants were lost after 5 years and the success rate was 95.1%. Patient enquiry revealed high satisfaction. CONCLUSION: Internal conical connection implants with platform-switched abutments presented a high success rate and preservation of marginal bone levels at the implant shoulder after 5 years of loading.

Evaluation of Sequential Urine Analysis when Selecting Candidates for Vesicoamniotic Shunting in Lower Urinary Tract Obstruction.

OBJECTIVE: The objective of our study was to assess the utility of sequential fetal urine analysis in severe lower urinary tract obstruction (LUTO) when selecting cases suitable for vesicoamniotic shunting. MATERIAL AND METHODS: This was a retrospective cohort study of cases of severe LUTO treated in our fetal medicine center from 1994 to 2013. Two fetal bladder samples were taken 24-48 h apart to assess renal function. A vesicoamniotic shunt was inserted in case of improvement in urinary biochemistry between the 2 samples. We assessed perinatal morbidity and mortality and renal function at 5 years. RESULTS: Among a total of 26 LUTO cases with sequential urine analysis, 5 showed normal urinary biochemistry, 13 were abnormal, and 8 improved between the 2 samples. These 8 cases underwent vesicoamniotic shunt placement, leading to the birth of 6/8 (75%) live infants, 5/6 (83%) of whom had normal renal function at 5 years. The 5 cases with normal biochemistry occasioned 2 neonatal deaths and 3 children with normal renal function at 5 years. Elective termination of pregnancy was requested by parents for the fetuses exhibiting abnormal biochemistry. CONCLUSION: An improvement in urinary biochemistry between 2 sequential fetal bladder punctures in severe LUTO could be an effective criterion in the selection of candidates for vesicoamniotic shunting. However, the benefit of a shunt in fetuses with normal amniotic fluid remains to be evaluated in clinical trials.

Effect of Cobalt and Chromium Ions on the Chlorhexidine Digluconate as Seen by Intermolecular Diffusion.

Metal ions such as cobalt (II) and chromium (III) might be present in the oral cavity, as a consequence of the corrosion of Co-Cr dental alloys. The diffusion of such metal ions into the organism, carried by saliva, can cause health problems as a consequence of their toxicity, enhanced by a cumulative effect in the body. The effect of the chlorhexidine digluconate, which is commonly used in mouthwash formulations, on the transport of these salts is evaluated in this paper by using the Taylor dispersion technique, which will allow an assessment of how the presence of chlorhexidine digluconate (either in aqueous solution or in a commercial formulation) may affect the diffusion of metal ions. The ternary mutual diffusion coefficients of metal ions (Co and Cr) in the presence of chlorhexidine digluconate, in an artificial saliva media, were measured. Significant coupled diffusion of CoCl2 (and CrCl3) and chlorhexidine digluconate is observed by analysis of the non-zero values of the cross-diffusion coefficients, D12 and D21. The observed interactions between metal ions and chlorhexidine digluconate suggest that the latter might be considered as an advantageous therapeutic agent, once they contribute to the reduction of the concentration of those ions inside the mouth.

Collagenated Porcine Heterologous Bone Grafts: Histomorphometric Evaluation of Bone Formation Using Different Physical Forms in a Rabbit Cancellous Bone Model.

Collagenated porcine-derived bone graft materials exhibit osteoconductive properties and the development of different formulations intends to enhance bone regeneration. This study aims to evaluate bone healing in a rabbit cancellous bone defect in response to grafting with different physicochemical forms of heterologous porcine bone. Twenty-six adult male New Zealand White rabbits received two critical size femoral bone defects per animal (n = 52), each randomly assigned to one of the five tested materials (Apatos, Gen-Os, mp3, Putty, and Gel 40). Animals were sacrificed at 15- and 30-days post-surgery. Qualitative and quantitative (new bone, particle and connective tissue percentages) histological analyses were performed. Histomorphometry showed statistically significant differences in all evaluated parameters between mp3 and both Putty and Gel 40 groups, regardless of the timepoint (p < 0.05). Moreover, statistical differences were observed between Apatos and both Putty (p = 0.014) and Gel 40 (p = 0.007) groups, at 30 days, in regard to particle percentage. Within each group, regarding new bone formation, mp3 showed significant differences (p = 0.028) between 15 (40.93 ± 3.49%) and 30 (52.49 ± 11.04%) days. Additionally, intragroup analysis concerning the percentage of particles revealed a significant reduction in particle occupied area from 15 to 30 days in mp3 and Gen-Os groups (p = 0.009). All mp3, Gen-Os and Apatos exhibited promising results in terms of new bone formation, thus presenting suitable alternatives to be used in bone regeneration.

Exploration of piperazine-derived thioureas as antibacterial and anti-inflammatory agents. In vitro evaluation against clinical isolates of colistin-resistant Acinetobacter baumannii.

A. baumannii is one of the most important multidrug-resistant microorganisms in hospital units. It is resistant to many classes of antibiotics and the development of new therapeutic strategies is necessary. The aim of this study was to evaluate the antibacterial activity of a set of piperazine-derived thioureas against 13 clinical strains of colistin-resistant A. baumannii. Six derivatives were identified to inhibit bacterial growth of 46% of the A. baumannii strains at low micromolar concentrations (Minimum Inhibitory Concentration from 1.56 to 6.25 µM). A common structural feature in most active compounds was the presence of a 3,5-bis-trifluoromethyl phenyl ring at the thiourea function. In addition, the ability of the compounds to inhibit production of nitric oxide (NO) was examined in RAW 264.7 murine macrophages, highlighting the potential of piperazine-derived thioureas as promising scaffolds for the design of new combined anti-bacterial/anti-inflammatory agents.

Comparison between conventional and computerised methods in the assessment of an occlusal scheme.

PURPOSE: In the definition of an occlusal scheme, clinicians should choose between conventional and computerised methods based on a careful appraise of the advantages and limitations. This study aims to assess the correlation between the two approaches in a clinical setting. METHODS: Twenty-four patients were included to compare different methods of occlusal contacts assessment on the posterior surfaces of flat mandibular appliances. In supine position, they were asked to clench with maximum strength, in the maximum intercuspation position with a 24 µm articulating paper positioned between the teeth and the appliance surface. An extra-oral photograph of the marks was taken (total N = 2082). They were visually classified based on a pre-defined scale (ie, conventional assessment) and with ImageJ analysis software (ie, photographic software assessment). Additionally, a computerised occlusal analysis was performed (ie, computerised assessment). Correlation analysis of the data achieved with conventional, photographic and computerised assessments was performed. RESULTS: Correlation between conventional and computerised assessments was weak (r = .265), whilst it was moderate between conventional and photographic assessments (r = .633), as well as between photographic and computerised assessments (r = .476). CONCLUSIONS: This investigation showed a weak-to-moderate correlation between different methods (ie, conventional, photographic and computerised) to assess occlusal marks. None of the three can actually be considered the standard of reference, but based on their specific features, it can bet suggested that the conventional method may be enough for most clinical purposes, unless otherwise proven.

Exome resequencing and GWAS for growth, ecophysiology, and chemical and metabolomic composition of wood of Populus trichocarpa.

BACKGROUND: Populus trichocarpa is an important forest tree species for the generation of lignocellulosic ethanol. Understanding the genomic basis of biomass production and chemical composition of wood is fundamental in supporting genetic improvement programs. Considerable variation has been observed in this species for complex traits related to growth, phenology, ecophysiology and wood chemistry. Those traits are influenced by both polygenic control and environmental effects, and their genome architecture and regulation are only partially understood. Genome wide association studies (GWAS) represent an approach to advance that aim using thousands of single nucleotide polymorphisms (SNPs). Genotyping using exome capture methodologies represent an efficient approach to identify specific functional regions of genomes underlying phenotypic variation. RESULTS: We identified 813 K SNPs, which were utilized for genotyping 461 P. trichocarpa clones, representing 101 provenances collected from Oregon and Washington, and established in California. A GWAS performed on 20 traits, considering single SNP-marker tests identified a variable number of significant SNPs (p-value < 6.1479E-8) in association with diameter, height, leaf carbon and nitrogen contents, and δ15N. The number of significant SNPs ranged from 2 to 220 per trait. Additionally, multiple-marker analyses by sliding-windows tests detected between 6 and 192 significant windows for the analyzed traits. The significant SNPs resided within genes that encode proteins belonging to different functional classes as such protein synthesis, energy/metabolism and DNA/RNA metabolism, among others. CONCLUSIONS: SNP-markers within genes associated with traits of importance for biomass production were detected. They contribute to characterize the genomic architecture of P. trichocarpa biomass required to support the development and application of marker breeding technologies.

Peri-implant marginal bone loss reduction with platform-switching components: 5-Year post-loading results of an equivalence randomized clinical trial.

AIM: To compare the clinical performance and marginal bone levels of implants restored with platform-switching (PS) or platform-matching (PM) abutments. MATERIALS AND METHODS: Adult patients missing two or more adjacent teeth in the posterior mandible received 2-4 CAMLOG SCREW-LINE implants and were randomly allocated to the PM or PS group, receiving the corresponding prosthetic components from surgery onwards. Implants were conventionally loaded with single cemented crowns. Patients were followed annually for 5 years. Outcome measures were marginal bone level changes, implant survival, performance of the prosthetic components and clinical parameters plaque index, sulcus bleeding index and pocket probing depth. RESULTS: Thirty-three patients received 72 implants in the PM group, and thirty-five patients received 74 implants in the PS group. Sixty patients attended the final appointment, 31 had received PS components and 29 had received PM components with 65 and 63 implants, respectively. Global survival rate was 96.6% with no differences between groups (p = 0.647). After 5 years of functional loading, PS restored implants presented 0.23mm (95% CI: [0.03, 0.43], p = 0.025) lower marginal bone level changes. The two groups were declared non-equivalent. CONCLUSION: Patients requiring implant supported restorations in healed bounded or free end edentulous gaps of the mandible benefit from the use of PS components in terms of peri-implant marginal bone level maintenance, though it may not be clinically noticeable.

Titanium dental implants with different collar design and surface modifications: A systematic review on survival rates and marginal bone levels.

AIM: The aim of this study was to compare clinical and radiographic outcomes of dental implants with different neck characteristics. METHODS: A protocol-oriented search aimed at the question: "In patients subjected to tooth replacement with screw-type dental implants does the modification of the implant neck macro- or microgeometry contribute to the improvement of survival rates and maintenance of the peri-implant marginal bone levels?" Primary outcomes were survival and marginal bone level (MBL) changes evaluated on randomized controlled trials with >10 participants and follow-up >1 year. Risk of bias was evaluated using the Cochrane Collaboration's tool. The review follows the PRISMA statement. RESULTS: Forty-three studies compared: (a) One- versus two-piece implants (N = 7); (b) Two-piece implants with different neck characteristics (machined and rough collars, microthreads, LASER microtexturing) (N = 21); (c) Two-piece implants with macrogeometry modifications (tapering, back-tapering, and scalloping) (N = 6). One- and two-piece implants showed similar survival (RR = 0.45, 95% CI: [0.12, 1.66], p = 0.23) and MBL changes (WMD = 0.09 mm, 95% CI: [-0.27, 0.45], p = 0.64) at 1-year post-loading. Machined collar implants have higher risk of early failure than rough collar implants (RR = 3.96, 95% CI: [1.12, 13.93], p = 0.03) and 0.43 mm higher bone resorption (95% CI: [0.0, 0.86], p = 0.05). Microthreads (WMD = 0.07 mm, 95% CI: [-0.01, 0.15], p = 0.10) and LASER microtexturing (WMD = 0.15 mm, 95% CI: [-0.35, 0.65], p = 0.56) do not reduce bone resorption. Scalloped implants have 1.26 mm higher resorption (95% CI: [0.72, 2.00], p < 0.001). CONCLUSIONS: One- and two-piece implants have similar survival and MBL changes. Rough collar implants have lower MBL changes than machined collar implants. Additional modifications to rough collars are irrelevant.

Immediate versus early loading protocols of titanium-zirconium narrow-diameter implants for mandibular overdentures in edentulous patients: 1-year results from a randomized controlled trial.

OBJECTIVES: The purpose of this randomized clinical trial was to compare immediate and early loading protocols for mandibular overdentures with two-splinted narrow-diameter implants in thin, non-augmented residual ridge situations. MATERIAL AND METHODS: Each edentulous patient received two implants in the interforaminal region. If primary stability after implant placement was achieved, patients were randomized either to the immediate (48 hr post-surgery) or the early (2 weeks after surgery) loading group. In prosthetic rehabilitation, a bar prosthetic system with a titanium bar was used. Implant survival, success rates, and radiographic changes at the crestal bone level were evaluated after 1 year, and patient satisfaction was recorded at 1 and 6 months post-surgery. RESULTS: Twenty-four patients with a mean age of 67 ± 9 years were included. One patient passed away after 11 months due to treatment-independent reasons. In the 24 implants of the immediate loading group, the mean bone level change from surgery/loading to the first-year evaluation was 0.32 ± 0.80 mm (p = .066). Regarding the early group (22 implants), the mean bone level change from loading to 1 year was 0.34 ± 0.69 mm (p = .048). After 1 year, no differences could be detected between groups (p = .91) with a mean difference of 0.02 mm (95% CI: [-0.42, 0.47]). The mean implant survival and success rates were 100% for both groups. Patient satisfaction was high; however, at 6 months, there was a difference between groups regarding the ability to chew. CONCLUSIONS: Both loading protocols for mandibular overdentures supported by two-splinted narrow-diameter implants were successful at the 1-year follow-up.

Influence of implant neck and abutment characteristics on peri-implant tissue health and stability. Oral reconstruction foundation consensus report.

OBJECTIVE: The aim of this consensus meeting was to assess the influence of implant neck and abutment characteristics on peri-implant tissue health and stability. MATERIAL AND METHODS: Group and plenary discussions were based on two systematic reviews focusing on the effect of titanium implants with different collar designs/surface modifications and the abutment material on the stability of marginal bone levels (MBLs), peri-implant health, and survival rates. RESULTS: The changes in MBLs were not influenced by the abutment material and were also similar at one- and two-piece implants after one year of loading. Rough collar implants improved MBLs in comparison to machined collar implants. Additional modifications of the collar had no beneficial clinical effect on MBLs. Titanium abutments were associated with significantly higher increases in bleeding on probing when compared with zirconia abutments. CONCLUSION: MBLs are mainly influenced by the microstructure (i.e., rough surfaced) of the implant neck. Consensus statements and specific recommendations for future research were elaborated during the consensus meeting.