Autotransplantation with Adjunctive Application of Enamel Matrix Derivatives Using a Digital Workflow: A Prospective Case Series.

OBJECTIVES: Digital protocols and bioactive materials may reduce complications and improve tooth autotransplantation (ATT) success and survival rates. This prospective study assesses the performance of a fully digital autotransplantation protocol of close-apex molars with the adjunctive application of Enamel Matrix Derivatives (EMD). METHODS: Twelve adult patients with 13 hopeless molar teeth were replaced with autotransplantation of closed apex third molars. Outcomes, including success and survival rates, clinical, endodontic, radiographic, patient-reported outcome measures (PROMs), and digital image assessments, were conducted over a two-year follow-up period. RESULTS: Survival and success rates were 100% and 91.2%, respectively, with no progressive inflammatory or replacement root resorption (ankylosis) except for one tooth presenting radiographic furcation involvement. A significant probing depth reduction of 2.4 ± 2.58 mm and CAL gains of 2.8 ± 3.03 mm were observed in transplanted teeth compared to the hopeless receptor teeth. Radiographic bone levels remained stable throughout the study period (-0.37 ± 0.66 mm), and digital image assessments showed minimal alveolar ridge width changes (-0.32 to -0.7 mm) and gingival margin changes (-0.95 to -1.27 mm) from baseline to last visit. PROMs indicated very high patient satisfaction. CONCLUSION: The use of a digital ATT protocol with adjunctive use of EMD in closed-apex third molars demonstrated promising short-term high success and survival rates. Additionally, this type of therapy adequately preserves the dimensions of the alveolar ridge in the receptor site.

Changes in the Fatty Acid Profile in Erythrocytes in High-Level Endurance Runners during a Sports Season.

Fatty acids (FAs) are an essential component of the erythrocyte membrane, and nutrition and physical exercise are two variables that affect their structure and function. The aim of this study was to evaluate the erythrocyte profile in a group of high-level endurance runners, as well as the changes in different FAs, throughout a sports season in relation to the training performed. A total of 21 high-level male endurance runners (23 ± 4 years; height: 1.76 ± 0.05) were evaluated at four different times throughout a sports season. The athletes had at least 5 years of previous experience and participated in national and international competitions. The determination of the different FAs was carried out by gas chromatography. The runners exhibited low concentrations of docosahexaenoic acid (DHA) and omega-3 index (IND ω-3), as well as high values of stearic acid (SA), palmitic acid (PA), and arachidonic acid (AA), compared to the values of reference throughout the study. In conclusion, training modifies the erythrocyte FA profile in high-level endurance runners, reducing the concentrations of polyunsaturated fatty acids (PUFAs) such as DHA and AA and increasing the concentrations of saturated fatty acids (SFAs) such as SA and the PA. High-level endurance runners should pay special attention to the intake of PUFAs ω-3 in their diet or consider supplementation during training periods to avoid deficiency.

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.

TDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression.

TAR DNA-binding protein 43 (TDP-43) proteinopathy in brain cells is the hallmark of amyotrophic lateral sclerosis (ALS) but its cause remains elusive. Asparaginase-like-1 protein (ASRGL1) cleaves isoaspartates, which alter protein folding and susceptibility to proteolysis. ASRGL1 gene harbors a copy of the human endogenous retrovirus HML-2, whose overexpression contributes to ALS pathogenesis. Here we show that ASRGL1 expression was diminished in ALS brain samples by RNA sequencing, immunohistochemistry, and western blotting. TDP-43 and ASRGL1 colocalized in neurons but, in the absence of ASRGL1, TDP-43 aggregated in the cytoplasm. TDP-43 was found to be prone to isoaspartate formation and a substrate for ASRGL1. ASRGL1 silencing triggered accumulation of misfolded, fragmented, phosphorylated and mislocalized TDP-43 in cultured neurons and motor cortex of female mice. Overexpression of ASRGL1 restored neuronal viability. Overexpression of HML-2 led to ASRGL1 silencing. Loss of ASRGL1 leading to TDP-43 aggregation may be a critical mechanism in ALS pathophysiology.

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.

Correction to: VEIN STEP: A Prospective, Observational, International Study to Assess Effectiveness of Conservative Treatments in Chronic Venous Disease.

Video Abstract.

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.

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.

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.

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.

Metabolites from the Andean paramo lichen Cladonia cf. didyma and their effect as photoprotective and antioxidant agents.

5α,8α-peroxyergosteryl divaricatinate (1) is isolated for the first time from acetone extract of the thallus of Cladonia cf. didyma together with condidymic (2), isodidymic (3) and barbatic (4) acids. Their UVB/UVA photoprotective and antioxidant activities were determined along with their cyto- and DNA-protecting actions against OH• damage. Compound 1 showed high UVA, cyto- (%cell viability ca. 82 at 15 µM vs 71 for OH•) and DNA (%DNA-integrity ca. 74 at 100 µM vs 22 for OH•) protecting properties. Compounds 2 and 3 exhibited high UVB (SPF ca. 40) and antioxidant activities (free radical scavenging potency EC50 = 0.6694 and 1.700 mol compound/mol DPPH•; ferric reducing power 0.392 and 0.546, at 500 ppm and inhibited lipid peroxidation); protecting cells (%cell viability ca. 76 at 15 µM) and DNA (%DNA-integrity ca. 57 at 100 µM). Compounds 1 to 3 fulfilled some physicochemical properties to act topically on the skin.

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.

Exploring the Influence of Spacers in EDTA-ß-Cyclodextrin Dendrimers: Physicochemical Properties and In Vitro Biological Behavior.

The synthesis of a new family of ethylenediaminetetraacetic acid (EDTA) core dimers and G0 dendrimers end-capped with two and four ß-cyclodextrin (ßCD) moieties was performed by click-chemistry conjugation, varying the spacers attached to the core. The structure analyses were achieved in DMSO-d6 and the self-inclusion process was studied in D2O by 1H-NMR spectroscopy for all platforms. It was demonstrated that the interaction with adamantane carboxylic acid (AdCOOH) results in a guest-induced shift of the self-inclusion effect, demonstrating the full host ability of the ßCD units in these new platforms without any influence of the spacer. The results of the quantitative size and water solubility measurements demonstrated the equivalence between the novel EDTA-ßCD platforms and the classical PAMAM-ßCD dendrimer. Finally, we determined the toxicity for all EDTA-ßCD platforms in four different cell lines: two human breast cancer cells (MCF-7 and MDA-MB-231), human cervical adenocarcinoma cancer cells (HeLa), and human lung adenocarcinoma cells (SK-LU-1). The new EDTA-ßCD carriers did not present any cytotoxicity in the tested cell lines, which showed that these new classes of platforms are promising candidates for drug delivery.

VEIN STEP: A Prospective, Observational, International Study to Assess Effectiveness of Conservative Treatments in Chronic Venous Disease.

INTRODUCTION: VEIN STEP was conducted to collect international data on the management of chronic venous disease (CVD) and to assess the effectiveness of conservative treatments for the relief of CVD signs and symptoms. METHODS: This international, observational, prospective, longitudinal, cohort study recruited adult outpatients consulting for symptomatic CVD. The primary objective was the effectiveness of conservative treatments on symptoms, signs and quality of life in a real-life setting assessed using a range of patient-reported outcome measures: 10-cm Visual Analog and Patient Global Impression of Change scales for symptoms; Venous Clinical Severity Score for physician assessment of signs; and 14-item ChronIc Venous Insufficiency Questionnaire (CIVIQ-14) for quality of life. At inclusion, patients were prescribed conservative treatment according to the physicians' usual practice. Follow-up visits took place at weeks 2 and 4, with an optional week 8 visit. RESULTS: The analysis set comprised 6084 subjects (78% female) from nine countries with a mean age of 50.6 ± 13.8 years and BMI of 28.0 ± 4.9 kg/m2. The most common CEAP classifications were C1 (23.0%), C2 (31.6%), and C3 (30.7%). Conservative therapy consisted of oral venoactive drugs (VADs; 95.8% of subjects) including micronized purified flavonoid fraction (MPFF 75.5%) and diosmin (18.8%), compression (52.0%), and topicals (31.5%). Conservative therapy led to global symptom improvement in 89% of patients after 2 weeks and 96% at 4 weeks. Pain, leg heaviness, cramps, and sensation of swelling were improved in 82%, 71%, 45.5%, and 46% of patients, respectively. Conservative therapy was associated with a decrease over time in patient-assessed global symptom intensity: - 2.37 ± 1.73 (P < 0.001) and physician-assessed disease severity - 1.83 ± 2.82 (P < 0.001). Among the VADs, MPFF-based conservative therapy was associated with the greatest reduction in symptom and sign intensity. Improvements in CIVIQ-14 were observed with all treatments but were greatest for MPFF. CONCLUSION: In this prospective study conducted in the real-world setting, treatment with conservative therapy, in particular MPFF, was associated with meaningful improvements in the clinical signs and symptoms of disease as well as in quality of life in patients with CVD. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04574375.

STUDY AIM: The VEIN STEP study aimed to gather global data on managing chronic venous disease (CVD) and evaluate the usefulness of conservative (non-surgical) treatments for improving CVD signs and symptoms. METHODS: Persons included in the study group had symptomatic CVD and were visiting outpatient clinics. The main aim was to measure how well treatments improved symptoms, physical signs of the illness, and quality of life. Different methods were used to measure these aspects, such as rating symptoms on a 10-point scale and using questionnaires completed by patients and doctors. STUDY FINDINGS: 6084 participants from nine countries joined the study. They were mostly women (78%) with an average age of around 50. Common symptoms included leg pain and leg heaviness. Treatments consisted mainly of drugs active on vein function, like MPFF and diosmin, along with compression stockings and creams. Conservative treatment led to symptom improvement in 89% of patients after 2 weeks and 96% at 4 weeks. Pain and leg heaviness improved in most patients (82% and 71% over the same period) while cramps, and swelling showed improvement in 45.5% and 46% of patients, respectively. Patients reported a significant decrease in symptom intensity, and doctors observed a reduction in disease severity. MPFF was associated with the highest reduction in symptom intensity. Improvements in quality of life were observed with all treatments but were greatest for MPFF. CONCLUSION: The study highlights that conservative treatments, especially MPFF, are associated with significant improvements in the clinical signs and symptoms of patients with CVD as well as in their quality of life.

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.

Evaluation of bacterial growth, effects on albumin, and coagulation factors in canine fresh frozen plasma administered as continuous rate infusion exposed to room temperature for 12 hours.

OBJECTIVES: To determine the risk of bacterial growth and to analyze the stability of albumin and coagulation factors in canine fresh frozen plasma (FFP) units exposed to room temperature (24°C) administered as a continuous rate infusion (CRI) for 12 hours. DESIGN: Ex vivo study. SETTING: University teaching hospital and pet blood bank. ANIMALS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An FFP CRI was simulated to replicate the standard routine procedure used in dogs. Plasma samples were collected before starting the CRI (H0), after 4 hours (H4), and after 12 hours (H12). Bacterial culture of FFP was performed and albumin concentration and specific activity levels for factors V, VII, VIII, and IX were measured and compared. All plasma culture results were negative. There were no statistically significant differences at any time point in the factor VIII activity (median 105.5% [range, 75.6%-142.0%] at H0; median 107.8% [range, 75.0%-172.7%] at H4; and median 112.1% [range, 81.7%-171.0%] at H12); factor IX activity (median 119.3% [range, 89.1%-175.9%] at H0; median 123.1% [range, 72.5%-172.7%] at H4; and median 118.3% [range, 86.6%-177.5%] at H12); or albumin concentration (median 21.0 g/L [range, 17.0-23.0 g/L] at H0 and median 20.0 g/L [range, 17.0-24.0 g/L] at H12). A slight but significant increase in factor V activity was observed when comparing H0 (median 107.0% [range, 71.0%-159.0%]) to H4 (median 117.7% [range, 71.0%-176.7%]) (P = 0.002) or H12 (median 116.2% [range, 71.0%-191.6%]) (P = 0.001). A slight but significant increase in factor VII activity was observed when comparing H0 (median 115.4% [range, 70.6%-183.7%]) to H4 (median 118.2% [range, 82.7%-194.6%]) (P = 0.005); H0 to H12 (median 128.7% [range, 86.4%-200.0%]) (P < 0.001); and H4 to H12 (P = 0.002). CONCLUSIONS: FFP CRI at room temperature for 12 hours could be considered safe with regard to risk for bacterial growth and also effective by providing albumin and clotting factors.

Pre-existing tumor host immunity characterization in resected non-small cell lung cancer.

INTRODUCTION: Neoadjuvant and adjuvant immune checkpoint blockade (ICB) have recently become standard of care in resectable non-small cell lung cancer (NSCLC). Yet, biomarkers that inform patients who benefit from this approach remain largely unknown. Here, we interrogated the tumor immune microenvironment (TIME) in early-stage NSCLC patients that underwent up-front surgery. METHODS: A total of 185 treatment-naïve patients with early-stage NSCLC, that underwent up-front surgical treatment between 2006 and 2018 at Hospital del Mar were included. 124 lung adenocarcinomas (LUADs), and 61 squamous cell carcinoma (LUSCs) were included in a tissue microarray. Immunohistochemistry for CD3, CD4, CD8, CD68, CD80, CD103, FOXP3, PD-1, PD-L1, PD-L2 and HLA class II were evaluated by digital image analysis (QuPath software). TIME was categorized into four groups using PD-L1 expression in tumor cells (<1 % or ≥1 %) and tumor resident memory (CD103+) immune cells (using the median as cut-off). We explored the association between different TIME dimensions and patient's clinicopathological features and outcomes. RESULTS: We found increased levels of T cell markers (CD3+, CD4+, CD8+ cells), functional immune markers (FOXP3+ cells) as well as, higher HLA-II tumor membrane expression in LUADs compared to LUSCs (p < 0.05 for all). In contrast, LUSCs displayed higher percentage of intratumor macrophages (CD68+ cells) as well as, higher PD-L1 and PD-L2 tumor membrane expression (p < 0.05 for all). Unsupervised analysis revealed three different tumor subsets characterized by membrane tumor expression of PD-L1, PD-L2 and HLA-class II. Enrichment of T cells (CD3+, CD8+ cells), regulatory T cells (FOXP3+ cells) and macrophages (CD68+ cells) was observed in the CD103+/PD-L1+ group (p < 0.05 for all). Multivariate analysis showed that infiltration by CD103+ immune cells was associated with improved OS (p = 0.009). CONCLUSIONS: TIME analysis in resected NSCLC highlighted differences by histology, PD-L1 expression and molecular subgroups. Biomarker studies using IHC might aid to individually tailor adjuvant treatment in early-stage NSCLC.

Synergy of Regenerative Periodontal Surgery and Orthodontics Improves Quality of Life of Patients with Stage IV Periodontitis: 24-Month Outcomes of a Multicenter RCT.

In stage IV periodontitis patients with pathologic tooth migration (PTM), interdisciplinary treatment includes regenerative periodontal surgery (RPS) with an application of biomaterials and orthodontic therapy (OT) to restore function, esthetics and thereby quality of life (QoL). In a 24-month randomized trial we explored the synergy between regenerative medicine and biomechanical force application. The following methods were used: Forty-three patients had been randomized to a combined treatment comprising RPS and subsequent OT starting either 4 weeks (early OT) or 6 months (late OT) post-operatively. Clinical periodontal parameters and oral health-related QoL (GOHAI) were recorded up to 24 months. We obtained the following results: Mean clinical attachment gain (∆CAL ± SD) was significantly higher with early OT (5.96 ± 2.1 mm) versus late OT (4.65 ± 1.76 mm) (p = 0.034). Pocket closure (PPD ≤ 4 mm) was obtained in 91% of defects with early OT compared to 90% with late OT. GOHAI-scores decreased significantly from 26.1 ± 7.5 to 9.6 ± 4.7 (early OT) and 25.1 ± 7.1 to 12.7 ± 5.6 (late OT). Inconclusion, teeth severely compromised by intrabony defects and PTM can be treated successfully by RPS followed by early OT with the advantage of an overall reduced treatment time. As a result of the combined periodontal-orthodontic therapy, the oral health-related QoL of patients was significantly improved. Early stimulation of wound healing with orthodontic forces had a favorable impact on the outcomes of regenerative periodontal surgery.

Crisis Communication during COVID-19: English, French, Portuguese, and Spanish Discourse of AstraZeneca Vaccine and Omicron Variant on Social Media.

Social media have been the arena of different types of discourse during the COVID-19 pandemic. We aim to characterize public discourse during health crises in different international communities. Using Tweetpy and keywords related to the research, we collected 3,748,302 posts from the English, French, Portuguese, and Spanish Twitter communities related to two crises during the pandemic: (a) the AstraZeneca COVID-19 vaccine, and (b) the Omicron variant. In relation to AstraZeneca, 'blood clot' was the main focus of public discourse. Using quantitative classifications and natural language processing algorithms, results are obtained for each language. The English and French discourse focused more on "death", and the most negative sentiment was generated by the French community. The Portuguese discourse was the only one to make a direct reference to a politician, the former Brazilian President Bolsonaro. In the Omicron crisis, the public discourse mainly focused on infection cases follow-up and the number of deaths, showing a closer public discourse to the actual risk. The public discourse during health crises might lead to different behaviours. While public discourse on AstraZeneca might contribute as a barrier for preventive measures by increasing vaccine hesitancy, the Omicron discourse could lead to more preventive behaviours by the public, such as the use of masks. This paper broadens the scope of crisis communication by revealing social media's role in the constructs of public discourse.