Impact of tissue factor expression and administration routes on thrombosis development induced by mesenchymal stem/stromal cell infusions: re-evaluating the dogma.

BACKGROUND: Hyperactive coagulation might cause dangerous complications such as portal vein thrombosis and pulmonary embolism after mesenchymal stem/stromal cell (MSC) therapy. Tissue factor (TF), an initiator of the extrinsic coagulation pathway, has been suggested as a predictor of this process. METHODS: The expression of TF and other pro- and anticoagulant genes was analyzed in xeno- and serum-free manufactured MSCs. Furthermore, culture factors affecting its expression in MSCs were investigated. Finally, coagulation tests of fibrinogen, D-dimer, aPPTs, PTs, and TTs were measured in patient serum after umbilical cord (UC)-MSC infusions to challenge a potential connection between TF expression and MSC-induced coagulant activity.  RESULTS: Xeno- and serum-free cultured adipose tissue and UC-derived MSCs expressed the highest level of TF, followed by those from dental pulp, and the lowest expression was observed in MSCs of bone marrow origin. Environmental factors such as cell density, hypoxia, and inflammation impact TF expression, so in vitro analysis might fail to reflect their in vivo behaviors. MSCs also expressed heterogeneous levels of the coagulant factor COL1A1 and surface phosphatidylserine and anticoagulant factors TFPI and PTGIR. MSCs of diverse origins induced fibrin clots in healthy plasma that were partially suppressed by an anti-TF inhibitory monoclonal antibody. Furthermore, human umbilical vein endothelial cells exhibited coagulant activity in vitro despite their negative expression of TF and COL1A1. Patients receiving intravenous UC-MSC infusion exhibited a transient increase in D-dimer serum concentration, while this remained stable in the group with intrathecal infusion. There was no correlation between TF expression and D-dimer or other coagulation indicators. CONCLUSIONS: The study suggests that TF cannot be used as a solid biomarker to predict MSC-induced hypercoagulation. Local administration, prophylactic intervention with anticoagulation drugs, and monitoring of coagulation indicators are useful to prevent thrombogenic events in patients receiving MSCs. Trial registration NCT05292625. Registered March 23, 2022, retrospectively registered, https://www. CLINICALTRIALS: gov/ct2/show/NCT05292625?term=NCT05292625&draw=2&rank=1 . NCT04919135. Registered June 9, 2021, https://www. CLINICALTRIALS: gov/ct2/show/NCT04919135?term=NCT04919135&draw=2&rank=1 .

An assessment of factors for the cruise port of call selection: The modified fuzzy Analytic Hierarchy Process.

Improving cruise ports of call is essential for enhancing the overall cruise experience for passengers, promoting tourism, and supporting the economic development of the regions served by these ports. Therefore, this article aims to assess selection factors (SFs) for the cruise port of call from the perspective of cruise operators (COs) and port operators (POs). In doing so, this paper first identifies SFs for the cruise port of call and establishes their hierarchical structure thanks to the extensive literature and expert brainstorming. Afterwards, The Modified Fuzzy Analytic Hierarchy Process (MFAHP) is developed to gauge the discrepancy in SFs between COs and POs. Empirical results from MFAHP pinpoint two significant SFs for POs to improve and attract their customers: customs, immigration control and quarantine (CIQ), and incentive measures. Besides, theoretical and managerial implications, and potential limitations for the next research are discussed.

Cytocompatibility and cell migration evaluation of calcium silicate-based root canal sealer compared to epoxide-amine resin sealer in stem cells from human apical papilla: An in-vitro study.

The purpose of this study was to assess the effect of a calcium silicate-based sealers (CeraSeal) and an epoxy resin-based sealer (AH Plus) on cytotoxicity and cell migration of stem cell from the human apical papilla (hSCAPs) by using the Alamar Blue, Annexin V-FICT and wound healing assays. In Alamar Blue assay, hSCAPs exposed to undiluted CeraSeal extract had significantly higher cell viability compared with that observed when cells were treated with AH Plus in all experimental period (p < 0.001). The flow cytometry analysis confirmed the comparison on viable cells and indicated that AH Plus increased apoptosis compared to CeraSeal and the control groups (p < 0.001). Additionally, AH Plus exhibited significantly lower level of cell migration than CeraSeal and the control for up to 48 h observation (p < 0.01). In summary, calcium silicate-based sealer (CeraSeal) is less cytotoxic and more biocompatible than epoxy resin-based sealer (AH Plus).

Edge magnetization and thermally induced spin current in nanostructured graphene.

In this work, the magnetic states and thermally induced spin currents in graphene nanoflake sizes with different sizes and shapes have been investigated using Hubbard model combined with non-equilibrium Green's function method. In addition to the antiferromagnetic (AFM) state governed by the sizes, shapes, armchair bond densities, and Coulomb energy, our calculations have also pointed out the emergence of ferromagnetic (FM) and complex magnetic states when the gate voltage is invoked in the graphene nanoflakes. More prominently, by exploiting the geometric symmetry of the nanoflakes without external fields, a pure spin current and zero charge current are generated in spin caloritronic device when the graphene nanoflakes are both in the AFM and FM states. The formation of pure spin currents driven by temperature difference depends on the graphene nanoflakes' size, shape, temperature and gate voltage as well. The study also shows the outstanding advantages of diamond-shaped graphene nanoflakes in both magnetic properties and spin currents. This result paves the way for the possibility of practical applications of graphene materials in spintronics and spin caloritronics.

Effects of advanced platelet-rich fibrin combined with xenogenic bone on human periodontal ligament stem cells.

OBJECTIVES: In this study, we aimed to investigate the effects of a mixture of advanced platelet-rich fibrin (A-PRF) and xenogenic bone substitute material (XBSM) on the proliferation and migration of human periodontal ligament stem cells (hPDLSCs) based on the in vitro release of growth factors. MATERIAL AND METHODS: The concentrations of platelet-derived growth factor-AB (PDGF-AB) and vascular endothelial growth factor (VEGF) released by the A-PRF-XBSM mixture were estimated using enzyme-linked immunoassay for up to 7 d. The A-PRF-XBSM mixture exudate was incubated with hPDLSCs. At Days 1, 3, 5, and 7, cell proliferation and migration were investigated by cell counting and wound-healing assays. RESULTS: PDGD-AB and VEGF were released from the A-PRF-XBSM mixture exudate for up to 7 days. hPDLSCs were cultured in media with various concentrations of the A-PRF-XBSM mixture exudate and exhibited their proliferation and migration ability. Furthermore, the factors released from the 100% A-PRF-XBSM mixture exudate had a substantial effect on cell migration, whereas those released from 4% and 20% A-PRF-XBSM mixture exudates stimulated hPDLSC proliferation. CONCLUSIONS: A-PRF-XBSM mixture continuously released growth factors over 7 days and enhanced hPDLSC proliferation and migration. Therefore, A-PRF in combination with XBSM might provide potential advantages for periodontal tissue regeneration.

Assessing port service quality: An application of the extension fuzzy AHP and importance-performance analysis.

It is argued that ports are playing a crucial role in developing nations' economy. Still, solutions to improving port service quality (PSQ) to boost ports' competitive capacity is questionable. Hence, this study aims to investigate port service quality (PSQ) by using integration of the extension Fuzzy Analytic Hierarchy Process and Importance-Performance Analysis (IPA) from port users' perspectives. From the relevant literature and expert interview, the hierarchical structure of PSQ embracing six dimensions with 29 criteria was first established. To test the research model, the Dong Nai port joint stock company (DNPC) and their port-service users were empirically investigated. It is found that: (1) the importance degree of dimensions is ranked as follow: empathy (21.07%), tangibles (20.15%), assurance (15.97%), reliability (15.54%), responsiveness (12.53%), diversity (14.74%); (2) for criteria of PSQ, top five criteria concerned by shipping companies and ocean freight forwarders comprise: "proactive provision of vessel schedules", "cargo handling facilities and equipment", "detailed schedule", "accuracy and consistency of schedules", and "geographical location"; (3) there are four service attributes (SAs) needing to prioritize for improvement, including "perfect transportation of cargos", "ability in dealing with cargo damage", "willingness in helping customers", "provision of special cargo-related services". The practical policy is that port authorities should transfer the limited resources from SAs in Quadrant IV to Quadrant II to enhance the PSQ.

BiodentineTM Full Pulpotomy in Mature Permanent Teeth with Irreversible Pulpitis and Apical Periodontitis.

Vital pulp therapy, including direct pulp capping and partial and full pulpotomy, is primarily indicated for immature or mature permanent teeth with reversible pulpitis. Mature permanent teeth with irreversible pulpitis are frequently treated with root canal therapy. This report presents two cases of full pulpotomy using BiodentineTM in mature permanent teeth with irreversible pulpitis and acute apical periodontitis. The periapical radiograph illustrated a deep carious lesion extended to the pulp with apical radiolucency lesion or widened periodontal ligament space. Full pulpotomy with a tricalcium silicate-based cement was chosen as the definitive treatment. After decayed tissue excavation under a rubber dam, the exposed pulp tissue was amputated to the level of the canal orifice with a new sterile bur. BiodentineTM was applied as the pulp capping agent after hemostasis was obtained and for temporary restoration. The clinical signs disappeared quickly after the treatment. After one month, the coronal part of the temporary restoration was removed, and a composite resin was placed over the capping agent as a final restoration. At two-year follow-ups, the teeth were asymptomatic. Radiographs showed healing of the periapical lesion and periodontal ligament. BiodentineTM full pulpotomy of mature permanent teeth with irreversible pulpitis and apical periodontitis can be an alternative option to root canal therapy.

Interventions to Enhance Adherence to Oral Antineoplastic Agents: A Scoping Review.

BACKGROUND: As new targeted oral antineoplastic therapies have emerged in recent years, the development of effective strategies that promote optimal adherence to cancer medication regimens has become an important priority. METHODS: We conducted a scoping literature review to search for English language articles published through July 15, 2019, to identify studies that reported the testing and/or evaluation of interventions to improve adherence to oral antineoplastic agents. RESULTS: A total of 56 articles were selected for review. Of the studies evaluated, 14 were randomized trials. All interventions except two targeted adult patients. Thirty-three studies enrolled fewer than 100 patients. Most interventions were education- and counseling-based and centered on provision of information about the drug and strategies to manage side effects. Only eight studies used an mHealth tool and/or text messages to target nonadherence. Among studies with a comparison sample, fewer than one-half (44.7%) reported statistically significant improvements in adherence or persistence associated with the intervention; however, some pharmacist-directed programs, particularly those that integrated monitoring or routine follow-up with a provider, did demonstrate efficacy. CONCLUSION: Although the development of adherence-promoting interventions for oral antineoplastic therapies has increased recently, few have been rigorously tested. The nascent literature suggests those that are pharmacist directed and use regular monitoring show promise, though additional prospective studies are needed. Study methodology, population selection, and potential challenges that may be encountered in the implementation and dissemination phases should be considered when developing new interventions to address nonadherence to oral antineoplastic treatment.

Risk factors of periodontal disease in Vietnamese patients.

AIM: The aim of the present study was to assess the association of periodontitis with dental and smoking behaviors, self-perception of oral status, dental knowledge, and obesity in Vietnamese patients. METHODS: A cross-sectional study was conducted on 367 adults who first visited the Faculty of Odonto-Stomatology, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam. Information on demographic characteristics, dental and smoking behaviors, self-perception of oral status, dental knowledge, and nutritional status was investigated by a self-administered questionnaire. Periodontal status, including plaque index, probing depth, and bleeding on probing, was examined. Multiple logistic regression analysis was performed to explore risk factors that were associated with periodontitis after adjusting for confounding factors. RESULTS: Dental and smoking behaviors, dental knowledge, and nutritional status were all significantly related to periodontitis. The multiple logistic regression analysis showed that patients who had risk factors significantly associated with periodontitis were those who had dental scaling during the past year (odds ratio [OR]: 2.2), current smokers (OR: 2.47), who received instructions on oral hygiene (OR=1.73), and those who were overweight/obese (OR: 4.78). CONCLUSION: Periodontitis was correlated with dental and smoking behaviors, dental knowledge, and nutritional status in Vietnamese dental patients. Promoting a healthy lifestyle, reducing tobacco consumption, motivating oral self-care behaviors, together with normal weight maintenance, are necessary to reduce periodontal disease burdens.

Simplified conditions for storing and cryopreservation of dental pulp stem cells.

OBJECTIVES: This study aimed to simplify the collection, isolation and cryopreservation procedure of human dental pulp stem cells (DPSCs) to ease the establishment of dental stem cell banking. DESIGN: Extracted third molars were collected and stored either in growth medium or in gentamicin-saline (480µg/ml) for 6, 9 or 12h. DPSCs were isolated and subjected to cryopreservation by a controlled-rate or rapid freezing method in 5 or 10% DMSO. Flow cytometry and growth pattern of DPSCs before and after cryopreservation were conducted. RESULTS: Rate of contamination by which the extracted teeth were stored in control and gentamicin-saline were 9.1% (N=33) and 2.3% (N=43), respectively. Successful cell isolation rate of teeth preserved in gentamicin-saline at 6h (92.9%) was comparable to those of growth media group (90.3%). At 9 and 12h, the rates dropped significantly to 75% and 54%, respectively. Cryopreservation by controlled-rate freezing either in 5 or 10% DMSO resulted in a significantly higher percentage of viable cells than by rapid freezing. Cells conserved by controlled-rate freezing in 5% DMSO showed a pattern of growth similar to control unfrozen cells; 10% DMSO significantly deteriorated the growth pattern of the cells. After thawing, DPSCs conserved by controlled-rate freezing still expressed stemness characteristics, although hematopoietic stem cell markers were slightly increased. CONCLUSION: Gentamicin-saline was effective in preserving human teeth for DPSC isolation. Controlled-rate freezing in 5% DMSO gave the highest rate of cell viability. This study simplifies the storage conditions and proposes a simple method for cryopreservation of DPSCs.

Salivary oxidative stress biomarkers in chronic periodontitis and acute coronary syndrome.

OBJECTIVES: The study aimed at assessing oxidative stress (OS) biomarker levels in the saliva of patients with chronic periodontitis (CP) and acute coronary syndrome (ACS) and establishing their correlation to periodontal parameters and markers for cardiovascular events. MATERIALS AND METHODS: The present study enrolled 24 patients with ACS and CP (the ACSCP group), 24 patients with ACS only (the ACS group), 24 patients with CP only (the CP group), and 24 healthy controls. Plaque index (PI), gingival index, bleeding on probing, probing pocket depth (PPD), and clinical attachment loss were recorded. Markers for cardiovascular events included serum high sensitivity C-reactive protein (hsCRP) and plasma fibrinogen. 8-Hydroxydeoxyguanosine (8-OHdG), protein carbonyl (PC), malondialdehyde (MDA), and total antioxidant capacity (TAOC) were used as OS biomarkers. RESULTS: Salivary 8-OHdG, MDA, and PC levels were significantly higher in the ACSCP, ACS, and CP groups than in healthy controls (p < 0.05). There were significant correlations between salivary PC levels and PI or PPD (p < 0.05) as well as between salivary 8-OHdG levels and all periodontal parameters (p < 0.05). TAOC levels in saliva were correlated to both serum hsCRP and plasma fibrinogen (p < 0.05). Salivary MDA levels were correlated to all periodontal parameters and biomarkers for cardiovascular events (p < 0.05). CONCLUSIONS: Salivary OS biomarker levels were higher in diseased groups compared to control. They also correlated to clinical periodontal parameters and markers for cardiovascular events in ACS patients, with or without CP. CLINICAL RELEVANCE: Salivary OS biomarkers could potentially serve as diagnostic tools for cardiovascular and/or periodontal diseases.

Salivary Lipid Peroxidation in Patients With Generalized Chronic Periodontitis and Acute Coronary Syndrome.

BACKGROUND: Lipid peroxidation is a major consequence of oxidative stress and can be evaluated via malondialdehyde (MDA) levels. The present study aims to assess MDA levels in the saliva of patients with chronic periodontitis (CP) and acute coronary syndrome (ACS) and establish their correlation with periodontal clinical parameters, serum high-sensitivity C-reactive protein (hsCRP), and plasma fibrinogen. METHODS: The study enrolled 64 patients stratified into four age- and sex-matched groups: both ACS and CP, ACS only, CP only, and healthy controls. All patients were examined, periodontal clinical parameters were recorded, and saliva and blood samples were collected. Salivary MDA levels were measured using a spectrophotometric assay. A quantitative turbidimetric test was used for the measurement of serum hsCRP levels, and plasma fibrinogen levels were determined using an automated analyzer. RESULTS: Salivary MDA levels were significantly higher in patients with both ACS and CP than in those with only ACS or only CP and healthy controls (P <0.05). There were significant positive correlations between salivary MDA levels and periodontal clinical parameters as well as biomarkers for cardiovascular events (P <0.001). CONCLUSIONS: To our knowledge, this study is the first to investigate salivary MDA levels in patients with ACS and their correlations with serum hsCRP and plasma fibrinogen levels. The results indicate that salivary MDA levels could be a biomarker for cardiovascular and/or periodontal disease.

Various methods for isolation of multipotent human periodontal ligament cells for regenerative medicine.

Periodontal ligament (PDL) is a specialized connective tissue that connects cementum and alveolar bone to maintain and support the teeth in situ and preserve tissue homeostasis. Recent studies have revealed the existence of stem cells in human dental tissues including periodontal ligament that play an important role, not only in the maintenance of the periodontium but also in promoting periodontal regeneration. In this study, human periodontal ligament cells (hPDLCs) were isolated by outgrowth and enzymatic dissociation methods. Expression of surface markers on PDLCs as human mesenchymal stem cells (MSCs) was identified by flow cytometry. In addition, proliferation and differentiation capacity of cultured cells to osteoblasts, adipocytes were evaluated. As a result, we successfully cultured cells from the human periodontal ligament tissues. PDLCs express mesenchymal stem cell (MSC) markers such as CD44, CD73, and CD90 and do not express CD34, CD45, and HLA-DR. PDLCs also possess the multipotential to differentiate into various types of cells, such as osteoblast and adipocytes, in vitro. Therefore, these cells have high potential to serve as materials for tissue engineering, especially dental tissue engineering.