A Minimally Invasive Surgical Procedure to Harvest Palate Periosteum as a Source of Mesenchymal Stromal/Stem Cells for Bone Tissue Engineering.

The aim of this study is to validate a minimally invasive surgical procedure to harvest palate periosteum as a source of tissue for mesenchymal stromal/stem cells. We performed a standardized procedure to harvest the palate periosteum in ten subjects, which consisted of a 3 mm disposable punch and a Molt periosteal elevator to harvest a small full-thickness fragment of soft tissue at the hard palate area, between the upper bicuspids, 3 to 4 mm apical to the cement enamel junction. The one-third inner portion was fragmented, and following standard cell culture procedures, the adherent cells were cultured for three passages, after obtaining 70-90% confluence. Cell morphology analysis, flow cytometry analysis, and viability and osteogenic differentiation assays were performed. In all 10 cases, uneventful healing was observed, with no need for analgesic intake. The evaluation of cell morphology showed elongated spindle-shaped cells distributed in woven patterns. A high viability range was verified as well as an immunophenotype compatible with mesenchymal stem cell lineage. The differentiation assay showed the potential of the cells to differentiate into the osteogenic lineage. These results demonstrate that the minimally invasive proposed surgical technique is capable of supplying enough periosteum source tissue for stem cell culture and bone tissue engineering.

Deep Learning for Echo Analysis, Tracking, and Evaluation of Mitral Regurgitation (DELINEATE-MR).

BACKGROUND: Artificial intelligence, particularly deep learning (DL), has immense potential to improve the interpretation of transthoracic echocardiography (TTE). Mitral regurgitation (MR) is the most common valvular heart disease and presents unique challenges for DL, including the integration of multiple video-level assessments into a final study-level classification. METHODS: A novel DL system was developed to intake complete TTEs, identify color MR Doppler videos, and determine MR severity on a 4-step ordinal scale (none/trace, mild, moderate, and severe) using the reading cardiologist as a reference standard. This DL system was tested in internal and external test sets with performance assessed by agreement with the reading cardiologist, weighted κ, and area under the receiver-operating characteristic curve for binary classification of both moderate or greater and severe MR. In addition to the primary 4-step model, a 6-step MR assessment model was studied with the addition of the intermediate MR classes of mild-moderate and moderate-severe with performance assessed by both exact agreement and ±1 step agreement with the clinical MR interpretation. RESULTS: A total of 61 689 TTEs were split into train (n=43 811), validation (n=8891), and internal test (n=8987) sets with an additional external test set of 8208 TTEs. The model had high performance in MR classification in internal (exact accuracy, 82%; κ=0.84; area under the receiver-operating characteristic curve, 0.98 for moderate/severe MR) and external test sets (exact accuracy, 79%; κ=0.80; area under the receiver-operating characteristic curve, 0.98 for moderate or greater MR). Most (63% internal and 66% external) misclassification disagreements were between none/trace and mild MR. MR classification accuracy was slightly higher using multiple TTE views (accuracy, 82%) than with only apical 4-chamber views (accuracy, 80%). In subset analyses, the model was accurate in the classification of both primary and secondary MR with slightly lower performance in cases of eccentric MR. In the analysis of the 6-step classification system, the exact accuracy was 80% and 76% with a ±1 step agreement of 99% and 98% in the internal and external test set, respectively. CONCLUSIONS: This end-to-end DL system can intake entire echocardiogram studies to accurately classify MR severity and may be useful in helping clinicians refine MR assessments.

Analysis of morphology and symmetry of the root canal system of incisors, premolars and mandibular molars using CBCT.

Knowledge of root canal internal anatomy and its variations is important forproper endodontic treatment. It is therefore necessary to investigate morphological aspects among different dental groups in the same patient to define the best protocol for the case. AIM: To evaluate the morphology and symmetry of homologous incisors, premolars and mandibular molars using cone beam computed tomography (CBCT). MATERIALS AND METHOD: Descriptive statistical analysis was performed for the frequency of categorical variables, and a chi-square test or Fisher 's exact test was used to test whether gender and side were associated with number of roots, number of canals, and Vertucci's classification. Forty-five CBCT scans were evaluated, and 444 mandibular teeth were analyzed. The number of roots, number of canals, classification of the canals in each root according to Vertucci and presence of a symmetrical relationship between pairs of posterior teeth were analyzed. RESULTS: The resuls showed that 74% of mandibular central incisors had type I root canal, 26% of mandibular lateral incisors had type I and, with a significant difference in the number of canals between males and females (p < 0.05). In mandibular first premolars, 70.5% had type I; and in mandibular second premolars, 98.5% had type I. Mandibular first molars had two roots in 98% of the cases. Second mandibular molars had two roots in 92.5% of the cases, one root in 6%, and three roots in 1.5%. Symmetry between central incisors was higher in females than in males. CONCLUSIÓN: Teeth of the same group can have different morphologies in the same patient.

0 conhecimento da anatomia interna e suas variagoes anatómicas é fator importante para o adequado tratamento endodóntico. Portanto, é necessário investigar esses aspectos morfológicos entre diferentes grupos dentários de um mesmo paciente para definir o melhor protocolo para o caso. OBJETIVO: Avaliar a morfologia e simetria de incisivos, pré-molares e molares inferiores homólogos por meio de tomografia computadorizada de feixe cónico (TCFC). MATERIAIS E MÉTODO: Foi realizada análise estatística descri-tiva para a frequéncia das variáveis categóricas e foi utilizado o teste do qui-quadrado ou teste exato de Fisher para testar a relagao entre sexo e lado em comparagao com número de raízes, número de canais e classificagao de Vertucci. Quarenta e cinco TCFC foram avaliadas e 444 dentes inferiores foram analisados. Foram considerados: o número de raízes, o número de canais, o tipo dos canais acordo com a classificagao de Vertucci e a presenga de relagao simétrica entre pares de dentes posteriores. RESULTADOS: Os resultados mostraram que 74% dos incisivos centrais inferiores tinham um canal radicular tipo 1 e 26% tinham dois canais; 73% dos incisivos laterais inferiores, 26%oeram do tipo I, tinham um canal e 27% tinham dois canais, com diferenga significativa no número de canais entre os grupos masculino e feminino (p < 0,05). Nos primeiros pré-molares inferiores, tipo I, um canal foi detectado em 70,5% e dois canais em 29,5%; nos segundos pré-molares inferiores, tipo I, um único canal foi detectado em 98,5%. O primeiro molar inferior foi observado com duas raízes em 98% e tres raízes em 2%o. O segundo molar inferior tinha duas raízes em 92,5% dos casos, uma raiz em 6% e tres raízes em 1,5%. A simetria foi maior nas mulheres em comparagao aos homens nos incisivos centrais. CONCLUSÃO: Pode-se concluir que dentes de um mesmo grupo podem apresentar morfologias diferentes no mesmo paciente.

Relationship between periapical lesions and sinus changes on multi-slice computed tomography sean.

Differentiating orofacial odontogenic pain/disorders from pain/disorders associated with maxillary sinusitis is important to avoid unnecessary dentalprocedures and to properly refer patients to colleagues/dentists and vice versa. AIM: To analyze the association between apical lesions and sinus changes and to evaluate the agreement between the diagnoses of an endodontist, a radiologist, an oral and maxillofacial surgeon, and an otolaryngologist. MATERIALS AND METHOD: 385 axial, coronal, and sagittal MSCT scans were selected using an image archiving andcommunication system (PACS). The examinations had been performed between 2018 and 2022. RESULTS: Apical lesions were observed in 36.10% of sinusitis cases, 73.8% of unilateralsinusitis cases, 48.7% of sinus floor discontinuity cases, and 67.2% of cases in which endodontic treatment had been performed. Agreement between the diagnoses made by the endodontist and those made by the other investigators was high for most study variables (k > 0.60). The exceptions were mucosal thickening, for which agreement between the endodontist and the other investigators was intermediate (k=0.397), and the presence of periapicallesions (k=0.010), previous endodontic treatment (k=0.013), and mucosal thickness (k=0.024), for which agreement between endodontists and radiologists was low. Conclusions: There was an association between sinus changes and apical lesions.

Diferenciar a dor/desordens odontogénicas orofaciais da dor/desordens as sociadas á sinusite maxilar é importante para evitar procedimentos odontológicos desnecessários e para encaminhar adequadamente os pacientes aos colegas/dentistas e vice-versa. OBJETIVO: Analisar a associagdo entre lesoes apicais e alteragóes sinusais e avaliar a concordáncia entre os diagnósticos de um endodontista, um radiologista, um cirurgido bucomaxilofacial e um otorrinolaringologista. MATERIAL E MÉTODO: foram avaliadas 385 imagens. RESULTADOS: Aslesoes apicais foram observadas em 36,10% dos casos de sinusite, em 73,8% dos casos de sinusite unilateral, em 48,7% dos casos de descontinuidade do assoalho do seio e em 67,2%odos casos em que o tratamento endodontico havia sido realizado. A concordancia entre os diagnósticos feitos pelo endodontista e os feitos pelos outros pesquisadores foi alta para a maioria das variáveis do estudo (k > 0,60). As excegoes foram o espessamento da mucosa, para o qual a concordáncia entre o endodontista e os outros pesquisadores foi intermediária (k=0,397) e a presenga delesoes periapicais (k=0,010), tratamento endodontico prévio (k=0,013) e espessura da mucosa (k=0,024), para os quais a concordáncia entre endodontistas e radiologistas foi baixa. CONCLUSÕES: Houve uma associagdo entre as alteragóes sinusais e aslesoes apicais.

Cellulose acetate scaffold coated with a hydroxyapatite/graphene oxide nanocomposite for application in tissue engineering.

The objective of this study was to synthesize and characterize porous Cellulose Acetate (CA) scaffolds using the electrospinning technique and functionalize the surface of the scaffolds obtained through the dip-coating method with a Hydroxyapatite (HA) nanocomposite and varying concentrations of graphene oxide (GO) for application in tissue engineering regeneration techniques. The scaffolds were divided into four distinct groups based on their composition: 1) CA scaffolds; 2) CAHAC scaffolds; 3) CAHAGOC 1.0% scaffolds; 4) CAHAGOC 1.5% scaffolds. Scaffold analyses were conducted using X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Raman Spectroscopy, Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM/EDS), and in vitro cell viability assays (WST). For the biological test analysis, Variance (two-way) was used, followed by Tukey's post-test (α = 0.05). The XRD results revealed the predominant presence of CaP phases in the CAHAC, CAHAGOC 1.0%, and CAHAGOC 1.5% groups, emphasizing the presence of HA in the scaffolds. FTIR demonstrated characteristics of cellulose and PO4 bands in the groups containing HA, confirming the presence of CaP in the synthesized materials, as also indicated by XRD. Raman spectroscopy showed the presence of D and G bands, consistent with GO, confirming the successful incorporation of the HAGO nanocomposite into the scaffolds. The micrographs displayed overlapping electrospun fibers, forming the three-dimensional structure in the produced scaffolds. It was possible to observe hydroxyapatite crystals filling some of these pores, creating a suitable structure for cell adhesion, proliferation, and nutrition, as corroborated by the results of in vitro tests. All scaffolds exhibited high cell viability, with significant cell proliferation. Even after 48 h, there was a slight reduction in the number of cells, but a noteworthy increase in cell proliferation was evident in the CAHAGOC 1.5% group after 48 h (p < 0.05). In conclusion, it can be affirmed that the produced scaffolds demonstrated physical and biological characteristics and properties capable of promoting cell adhesion and proliferation. Therefore, they represent significant potential for application in tissue engineering, offering a new perspective regarding techniques and biomaterials applied in regenerative therapies.

Genome-Wide Association Study of Treatment-Resistant Depression: Shared Biology With Metabolic Traits.

OBJECTIVE: Treatment-resistant depression (TRD) occurs in roughly one-third of all individuals with major depressive disorder (MDD). Although research has suggested a significant common variant genetic component of liability to TRD, with heritability estimated at 8% when compared with non-treatment-resistant MDD, no replicated genetic loci have been identified, and the genetic architecture of TRD remains unclear. A key barrier to this work has been the paucity of adequately powered cohorts for investigation, largely because of the challenge in prospectively investigating this phenotype. The objective of this study was to perform a well-powered genetic study of TRD. METHODS: Using receipt of electroconvulsive therapy (ECT) as a surrogate for TRD, the authors applied standard machine learning methods to electronic health record data to derive predicted probabilities of receiving ECT. These probabilities were then applied as a quantitative trait in a genome-wide association study of 154,433 genotyped patients across four large biobanks. RESULTS: Heritability estimates ranged from 2% to 4.2%, and significant genetic overlap was observed with cognition, attention deficit hyperactivity disorder, schizophrenia, alcohol and smoking traits, and body mass index. Two genome-wide significant loci were identified, both previously implicated in metabolic traits, suggesting shared biology and potential pharmacological implications. CONCLUSIONS: This work provides support for the utility of estimation of disease probability for genomic investigation and provides insights into the genetic architecture and biology of TRD.

Association of chest computed tomography severity score at ICU admission and respiratory outcomes in critically ill COVID-19 patients.

OBJECTIVE: To evaluate the association of a validated chest computed tomography (Chest-CT) severity score in COVID-19 patients with their respiratory outcome in the Intensive Care Unit. METHODS: A single-center, prospective study evaluated patients with positive RT-PCR for COVID-19, who underwent Chest-CT and had a final COVID-19 clinical diagnosis needing invasive mechanical ventilation in the ICU. The admission chest-CT was evaluated according to a validated Chest-CT Severity Score in COVID-19 (Chest-CTSS) divided into low ≤50% (<14 points) and >50% high (≥14 points) lung parenchyma involvement. The association between the initial score and their pulmonary clinical outcomes was evaluated. RESULTS: 121 patients were clustered into the > 50% lung involvement group and 105 patients into the ≤ 50% lung involvement group. Patients ≤ 50% lung involvement (<14 points) group presented lower PEEP levels and FiO2 values, respectively GEE P = 0.09 and P = 0.04. The adjusted COX model found higher hazard to stay longer on invasive mechanical ventilation HR: 1.69, 95% CI, 1.02-2.80, P = 0.042 and the adjusted logistic regression model showed increased risk ventilator-associated pneumonia OR = 1.85 95% CI 1.01-3.39 for COVID-19 patients with > 50% lung involvement (≥14 points) on Chest-CT at ICU admission. CONCLUSION: COVID-19 patients with >50% lung involvement on Chest-CT admission presented higher chances to stay longer on invasive mechanical ventilation and more chances to developed ventilator-associated pneumonia.

In vitro study of structural and chemical changes in two reciprocating files after multiple reuses and sterilisation.

To use scanning electron microscopy and energy dispersive X-ray spectroscopy to evaluate the metallurgical-chemical changes of WaveOne Gold (WOG) and R-Motion (RM), after multiple uses. The instruments were divided into groups (n = 8): WOG and RM-control groups, new instruments; WOG1 and RM1; WOG2 and RM2; WOG3 and RM3 after instrumentation of 1, 2 or 3 molars, respectively. Burrs occurred mainly in the control group and after the first use. The RM files were found to have a higher nickel content, which increased during reuse, and a decrease in oxygen content with increasing reuse, in addition to calcium impregnation, which occurred in greater amounts in the corrosion areas in the WOG files. The presence of topographic and chemical changes was demonstrated, indicating that caution should be taken when reusing endodontic instruments to avoid fractures.

Influence of Passive Ultrasonic Irrigation of the Photosensitizer Used in Photodynamic Therapy on Microbial Reduction in the Root Canal System: An in Vitro Study.

Introduction: The success of endodontic treatment is based on microbial reduction promoted by the interaction of chemical and mechanical procedures. Photodynamic therapy (PDT) is used as an adjunct to conventional treatment, with significant microbial reduction. This study aimed to evaluate the influence of passive ultrasonic irrigation (PUI) of the photosensitizer (PS) used in PDT on microbial reduction in the root canal system. Materials and Methods: Forty-five mesiobuccal root canals from extracted human mandibular molars that were inoculated with standard strains of Enterococcus faecalis, Candida albicans, and Streptococcus mutans for 21 days were selected. The root canals were prepared using the ProTaper Next system and randomly divided into 3 groups (n=15): 1) PDT: PDT alone; 2) PUI+PDT: PUI followed by PDT; and 3) PUI/PS+PDT: PUI of the PS followed by PDT. Microbiological samples were collected from the canals before and after using the protocols described above. The data were analyzed by analysis of variance (Tukey's test) at a significance level of 5%. Results: Microbial counts before PDT, PUI+PDT, and PUI/PS+PDT did not differ significantly (P>0.05), showing methodological standardization in the microbial contamination of the root canal system. There was a significant reduction in microbial counts after PDT (61.05%), PUI+PDT (65.04%), and PUI/PS+PDT (68.58%) (P<0.01), but with no statistically significant difference between the three groups (P>0.05). Conclusion: Based on the present findings, it was concluded that the combination of PUI with PDT or PS activation did not influence microbial reduction achieved by PDT alone.

Effects of foam roller on pain intensity in individuals with chronic and acute musculoskeletal pain: a systematic review of randomized trials.

OBJECTIVE: To analyze the effects of using foam roller on pain intensity in individuals with chronic and acute musculoskeletal pain. METHODS: This systematic review was registered in the National Institute for Health Research's prospective online registry of systematic reviews (PROSPERO) under CRD42023456841. The databases Pubmed, Medline (via Ovid), Embase, BVS, and PEDro (Physiotherapy Evidence Database) were consulted to carry out this systematic review. Notably, the records of clinical trials characterized as eligible were manually searched. The search terms were: (foam rolling OR foam rolling vibration) AND (acute musculoskeletal pain) AND (chronic musculoskeletal pain). The search was performed until August 22, 2023. For the analysis of the methodological quality, the PEDro scale was used for each of the manuscripts included in the systematic review. Due to the heterogeneity in the studies included in this systematic review, performing a meta-analysis of the analyzed variables was impossible. RESULTS: Only six manuscripts were eligible for data analysis. The type of FR used was non-vibrational, being applied by a therapist in only one of the manuscripts. With an application time ranging from at least 45 s to 15 min, the non-vibrational FR was applied within a day up to six weeks. Using the PEDro scale, scores were assigned that varied between 4 and 8 points, with an average of 6 ± 1.29 points. Only two randomized clinical trials found a significant benefit in pain intensity of adding FR associated with a therapeutic exercise protocol in individuals with patellofemoral pain syndrome and chronic neck pain. CONCLUSION: The results of this systematic review do not elucidate or reinforce the clinical use of FR in pain intensity in individuals with chronic and acute musculoskeletal pain.

Patterns of Chlamydia trachomatis and Neisseria gonorrhoeae in different anatomical sites among Pre-Exposure Prophylaxis (PrEP) users in Brazil.

BACKGROUND: The presence of untreated sexually transmitted infections (STIs) significantly increases the chance of acquiring HIV. In Brazil, testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) among Pre-Exposure Prophylaxis (PrEP) users is insufficient, and syndromic treatment is a priority in clinical practice. Multi-site testing for CT/NG improves thescreening of asymptomatic cases and ensures timely treatment. Therefore, it is essential for HIV prevention. This study aims to test the importance of two-site testing for better screening of these pathogens and to determine whether the presence of symptoms is an indicator of CT/NG infection. METHODS: This is a cross-sectional study carried out in four public infectious diseases clinics in São Paulo State, Brazil between January of 2022 and March of 2023. All participants had an anal swab and a first-pass or mid-stream urine collected for CT/NG analysis by Polymerase chain reaction (PCR). Data about sociodemographic, sexual behavioural and clinical aspects were collected. Pathway analysis was used to examine the direct and indirect relationships between variables according to the theoretical model. RESULTS: We screened 171 PrEP users which had two samples collected, resulting in 342 samples. Comparing the anatomic sites, the urine samples showed lower sensitivity for CT and NG than anal samples. Gonorrhoea was directly linked to lower age (ß= -0.161, p = 0.001). Time of PrEP use was directly associated with CT infection (ß = 0.202; p = 0.042) and inversely associated with dysuria (ß= -0.121, p = 0.009). Lower occurrence of yellow-green secretion was linked to detection of CT (ß= -0.089, p = 0.005) and NG (ß= -0.048, p = 0.002) infections. Foul-smelling discharge was directly associated with CT (ß = 0.275, p = 0.004) and NG (ß = 0.295, p = 0.037) infection. CONCLUSION: The symptoms are a bad indicator of CT and NG infection, and the screening must be done in more than one site since most of the positive results would be missed if only urines were tested. In the case of testing only one anatomical site, specifically the urethra, the CT/NG incidence and prevalence would be underestimated. The two-sites testing improves detection rates of CT/NG, and PrEP follow-up benefits people offering STI testing.

Whole-exome sequencing in UK Biobank reveals rare genetic architecture for depression.

Nearly two hundred common-variant depression risk loci have been identified by genome-wide association studies (GWAS). However, the impact of rare coding variants on depression remains poorly understood. Here, we present whole-exome sequencing analyses of depression with seven different definitions based on survey, questionnaire, and electronic health records in 320,356 UK Biobank participants. We showed that the burden of rare damaging coding variants in loss-of-function intolerant genes is significantly associated with risk of depression with various definitions. We compared the rare and common genetic architecture across depression definitions by genetic correlation and showed different genetic relationships between definitions across common and rare variants. In addition, we demonstrated that the effects of rare damaging coding variant burden and polygenic risk score on depression risk are additive. The gene set burden analyses revealed overlapping rare genetic variant components with developmental disorder, autism, and schizophrenia. Our study provides insights into the contribution of rare coding variants, separately and in conjunction with common variants, on depression with various definitions and their genetic relationships with neurodevelopmental disorders.

Development and multi-site external validation of a generalizable risk prediction model for bipolar disorder.

Bipolar disorder is a leading contributor to disability, premature mortality, and suicide. Early identification of risk for bipolar disorder using generalizable predictive models trained on diverse cohorts around the United States could improve targeted assessment of high risk individuals, reduce misdiagnosis, and improve the allocation of limited mental health resources. This observational case-control study intended to develop and validate generalizable predictive models of bipolar disorder as part of the multisite, multinational PsycheMERGE Network across diverse and large biobanks with linked electronic health records (EHRs) from three academic medical centers: in the Northeast (Massachusetts General Brigham), the Mid-Atlantic (Geisinger) and the Mid-South (Vanderbilt University Medical Center). Predictive models were developed and valid with multiple algorithms at each study site: random forests, gradient boosting machines, penalized regression, including stacked ensemble learning algorithms combining them. Predictors were limited to widely available EHR-based features agnostic to a common data model including demographics, diagnostic codes, and medications. The main study outcome was bipolar disorder diagnosis as defined by the International Cohort Collection for Bipolar Disorder, 2015. In total, the study included records for 3,529,569 patients including 12,533 cases (0.3%) of bipolar disorder. After internal and external validation, algorithms demonstrated optimal performance in their respective development sites. The stacked ensemble achieved the best combination of overall discrimination (AUC = 0.82-0.87) and calibration performance with positive predictive values above 5% in the highest risk quantiles at all three study sites. In conclusion, generalizable predictive models of risk for bipolar disorder can be feasibly developed across diverse sites to enable precision medicine. Comparison of a range of machine learning methods indicated that an ensemble approach provides the best performance overall but required local retraining. These models will be disseminated via the PsycheMERGE Network website.

Comparative in vitro analysis of the antifungal activity of different calcium silicate-based endodontic sealers

Aim: This study aimed to perform an in vitro comparative analysis of the antifungal activity of different calcium silicate-based endodontic sealers against three fungal species. Methods: The antifungal properties of three calcium silicate-based sealers were tested: Bio-C Sealer, Cambiar a Sealer Plus BC, and MTA-Fillapex. Two commonly used sealers were used as controls: AH Plus and Endomethasone. An agar diffusion test was performed to analyze the antifungal activity of the sealers against Candida albicans, Candida glabrata, Candida tropicalis, and a mixed microbial culture medium. The results were analyzed using ANOVA (p <0.05). Results: Endomethasone exhibited the highest inhibition against all strains examined, maintaining a consistent level of inhibition throughout 7 days. MTA-Fillapex demonstrated the best performance among the calcium silicate-based sealers for the three fungal species (p < 0.05), maintaining stable values over the 7 days, surpassing that of Endomethasone. Nevertheless, MTA-Fillapex only exhibited antimicrobial effect against the mixed culture for the first 24 hours, and no antimicrobial activity was observed at 48 hours, being surpassed by all tested sealers (p < 0.05). Conclusion: Of all silicate-based sealers tested, only MTA-Fillapex exhibited promising antifungal activity. Nevertheless, care must be taken when extrapolating these results, as MTA-Fillapex exhibited poor antimicrobial activity when tested in mixed microbial cultures

Evaluation of the apical sealing of an eggshell hydroxyapatite-based sealer.

Background: The success of endodontic treatment can be influenced by the type of endodontic sealer used, as certain sealers may be prone to apical microleakage, leading to treatment failure. The limitations of currently available sealers necessitate the development of new materials to improve the success rate of endodontic treatment. Therefore, the objective of this study was to assess the apical microleakage of newly developed hydroxyapatite-based endodontic sealers, including one derived from eggshells, and compare them with other commercially available sealers. Material and Methods: Eighty-five extracted human upper anterior teeth were selected for this study. The teeth were divided into 5 experimental groups and 2 control groups. The experimental groups were designated as follows: (1) HPSINT - obturated with gutta-percha cone and synthetic hydroxyapatite-based sealer, (2) BIOC - obturated with gutta-percha cone and Bio C-Sealer sealer, (3) AHPLUS-BC - obturated with gutta-percha cone and AHPLUS Bioceramic sealer, (4) AHP - obturated with gutta-percha cone and AHPLUS sealer, and (5) HPO - obturated with gutta-percha cone and sealer based on hydroxyapatite extracted from eggshells. Additionally, there were positive and negative control groups consisting of instrumented teeth filled with gutta-percha cones without any sealer and instrumented teeth without any filling, respectively. Methylene blue dye penetration was used to assess apical microleakage. Descriptive statistical analysis and Shapiro-Wilk normality test were applied to the observed results. As the samples followed a normal distribution, the ANOVA test was applied. Results: The control groups confirmed the validity of the experimental method, while the experimental groups showed varying degrees of dye penetration. The group obturated with Bio C-Sealer exhibited the highest mean apical microleakage, while AHPLUS Bioceramic sealer demonstrated lower mean than AHPLUS sealer and sealer based on hydroxyapatite extracted from eggshells (p<0.05). Finally, there was no difference between the synthetic hydroxyapatite-based sealer and AHPLUS Bioceramic sealer, AHPLUS sealer and sealer based on hydroxyapatite extracted from eggshells (p>0.05). No significant difference was observed between the hydroxyapatite-based sealers and the AHPLUS-BC sealer. Conclusions: The results of this study suggest that the newly developed hydroxyapatite-based endodontic sealers, including the one derived from eggshells, may have a lower risk of apical microleakage compared to other commercially available sealers. These findings highlight the potential of hydroxyapatite-based sealers to improve the success rate of endodontic treatment. Further research and clinical studies are warranted to validate these results and explore the long-term effects of these novel sealers. Key words:Endodontic treatment, apical microleakage, endodontic sealer, hydroxyapatite, eggshell-derived sealer.

Association Between Psychiatric Polygenic Scores, Healthcare Utilization and Comorbidity Burden.

Purpose: To estimate the association of psychiatric polygenic scores with healthcare utilization and comorbidity burden. Methods: Observational cohort study (N = 118,882) of adolescent and adult biobank participants with linked electronic health records (EHRs) from three diverse study sites; (Massachusetts General Brigham, Vanderbilt University Medical Center, Geisinger). Polygenic scores (PGS) were derived from the largest available GWAS of major depressive depression, bipolar disorder, and schizophrenia at the time of analysis. Negative binomial regression models were used to estimate the association between each psychiatric PGS and healthcare utilization and comorbidity burden. Healthcare utilization was measured as frequency of emergency department (ED), inpatient (IP), and outpatient (OP) visits. Comorbidity burden was defined by the Elixhauser Comorbidity Index and the Charlson Comorbidity Index. Results: Participants had a median follow-up duration of 12 years in the EHR. Individuals in the top decile of polygenic score for major depressive disorder had significantly more ED visits (RR=1.22, 95% CI; 1.17, 1.29) compared to those the lowest decile. Increases were also observed with IP and comorbidity burden. Among those diagnosed with depression and in the highest decile of the PGS, there was an increase in all utilization types (ED: RR=1.56, 95% CI 1.41, 1.72; OP: RR=1.16, 95% CI 1.08, 1.24; IP: RR=1.23, 95% CI 1.12, 1.36) post-diagnosis. No clinically significant results were observed with bipolar and schizophrenia polygenic scores. Conclusions: Polygenic score for depression is modestly associated with increased healthcare resource utilization and comorbidity burden, in the absence of diagnosis. Following a diagnosis of depression, the PGS was associated with further increases in healthcare utilization. These findings suggest that depression genetic risk is associated with utilization and burden of chronic disease in real-world settings.

Conditioned Media from Human Pulp Stem Cell Cultures Improve Bone Regeneration in Rat Calvarial Critical-Size Defects.

The aim of this study was to test whether lyophilized conditioned media from human dental pulp mesenchymal stem cell cultures promote the healing of critical-size defects created in the calvaria of rats. Prior to the surgical procedure, the medium in which dental pulp stem cells were cultured was frozen and lyophilized. After general anesthesia, an 8 mm diameter bone defect was created in the calvaria of twenty-four rats. The defects were filled with the following materials: xenograft alone (G1) or xenograft associated with lyophilized conditioned medium (G2). After 14 or 42 days, the animals were euthanized, and the specimens processed for histologic and immunohistochemical analysis. Bone formation at the center of the defect was observed only in the G2 at 42 days. At both timepoints, increased staining for VEGF, a marker for angiogenesis, was observed in G2. Consistent with this, at 14 days, G2 also had a higher number of blood vessels detected by immunostaining with an anti-CD34 antibody. In conclusion, conditioned media from human dental pulp mesenchymal stem cell cultures had a positive effect on the regenerative process in rat critical-size bone defects. Both the formation of bone and enhancement of vascularization were stimulated by the conditioned media.

Biomineralization of calcium phosphates functionalized with hydroxyapatite-binding peptide.

Functionalization of calcium phosphates with biomimetic peptides is a promising strategy to increase cellular response for bone tissue repair. In this work, biphasic calcium phosphate pellets were functionalized with the hydroxyapatite-binding peptide pVTK by dropping a suspension of the peptide on the pellet surface. The bioactivity tests were performed in vitro by using McCoy culture medium. Cytotoxicity tests were also performed to assess cell viability. The material was characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy with field emission gun (FEG-SEM). The results showed that functionalization with the biomimetic peptide was most effective in inducing precipitation of bone-like apatite on the pellets surface, when compared to the control groups (two positive control groups and one negative control group). Cytotoxicity tests showed that all samples are biocompatible but the pellets with peptide showed the highest values of cell viability.

Evaluating the relationship between the type of rescue medication and the adequacy of asthma maintenance therapy.

INTRODUCTION: Current guidelines incorporate the option of a rapid onset bronchodilator (ROB) plus an inhaled corticosteroid (ICS) for the relief of asthma symptoms, but there is doubt whether the combined therapy for relief could lead to suboptimal maintenance therapy since individuals might prefer it to the maintenance therapy. The objective of this study was to assess whether the type of rescue medication that the individual with asthma has available is associated with suboptimal maintenance therapy. METHODS: This cross-sectional study included non-smokers with asthma, ≥12 years old. The individuals attended an appointment with a physician, responded questionnaires and performed a spirometry. Adjusted regression analysis evaluated whether the type of rescue medication was associated with suboptimal maintenance therapy. RESULTS: We enrolled 953 individuals, of which 221 reported having no rescue medication, 171 carried any ROB + ICS for symptoms relief and 561 carried SABA alone to rescue. The frequency of suboptimal maintenance therapy was not different between individuals carrying the combination and those carrying SABA alone for symptoms relief, but individuals who reported having no rescue medication had less suboptimal maintenance therapy (P < 0.01). CONCLUSIONS: The frequency of suboptimal maintenance therapy for asthma was similar between individuals carrying any ROB + ICS for symptoms relief and those carrying SABA alone to rescue, whilst it was less frequent in the group that reported not having any reliever medication. Data from this study indicate that recent changes in asthma guidelines regarding the use of rescue medication have little risk of impairing maintenance therapy.

In Vivo Evaluation of Collagen and Chitosan Scaffold, Associated or Not with Stem Cells, in Bone Repair.

Natural polymers are increasingly being used in tissue engineering due to their ability to mimic the extracellular matrix and to act as a scaffold for cell growth, as well as their possible combination with other osteogenic factors, such as mesenchymal stem cells (MSCs) derived from dental pulp, in an attempt to enhance bone regeneration during the healing of a bone defect. Therefore, the aim of this study was to analyze the repair of mandibular defects filled with a new collagen/chitosan scaffold, seeded or not with MSCs derived from dental pulp. Twenty-eight rats were submitted to surgery for creation of a defect in the right mandibular ramus and divided into the following groups: G1 (control group; mandibular defect with clot); G2 (defect filled with dental pulp mesenchymal stem cells-DPSCs); G3 (defect filled with collagen/chitosan scaffold); and G4 (collagen/chitosan scaffold seeded with DPSCs). The analysis of the scaffold microstructure showed a homogenous material with an adequate percentage of porosity. Macroscopic and radiological examination of the defect area after 6 weeks post-surgery revealed the absence of complete repair, as well as absence of signs of infection, which could indicate rejection of the implants. Histomorphometric analysis of the mandibular defect area showed that bone formation occurred in a centripetal fashion, starting from the borders and progressing towards the center of the defect in all groups. Lower bone formation was observed in G1 when compared to the other groups and G2 exhibited greater osteoregenerative capacity, followed by G4 and G3. In conclusion, the scaffold used showed osteoconductivity, no foreign body reaction, malleability and ease of manipulation, but did not obtain promising results for association with DPSCs.