Emerging polymeric materials for treatment of oral diseases: design strategy towards a unique oral environment.

Oral diseases are prevalent but challenging diseases owing to the highly movable and wet, microbial and inflammatory environment. Polymeric materials are regarded as one of the most promising biomaterials due to their good compatibility, facile preparation, and flexible design to obtain multifunctionality. Therefore, a variety of strategies have been employed to develop materials with improved therapeutic efficacy by overcoming physicobiological barriers in oral diseases. In this review, we summarize the design strategies of polymeric biomaterials for the treatment of oral diseases. First, we present the unique oral environment including highly movable and wet, microbial and inflammatory environment, which hinders the effective treatment of oral diseases. Second, a series of strategies for designing polymeric materials towards such a unique oral environment are highlighted. For example, multifunctional polymeric materials are armed with wet-adhesive, antimicrobial, and anti-inflammatory functions through advanced chemistry and nanotechnology to effectively treat oral diseases. These are achieved by designing wet-adhesive polymers modified with hydroxy, amine, quinone, and aldehyde groups to provide strong wet-adhesion through hydrogen and covalent bonding, and electrostatic and hydrophobic interactions, by developing antimicrobial polymers including cationic polymers, antimicrobial peptides, and antibiotic-conjugated polymers, and by synthesizing anti-inflammatory polymers with phenolic hydroxy and cysteine groups that function as immunomodulators and electron donors to reactive oxygen species to reduce inflammation. Third, various delivery systems with strong wet-adhesion and enhanced mucosa and biofilm penetration capabilities, such as nanoparticles, hydrogels, patches, and microneedles, are constructed for delivery of antibiotics, immunomodulators, and antioxidants to achieve therapeutic efficacy. Finally, we provide insights into challenges and future development of polymeric materials for oral diseases with promise for clinical translation.

Bayesian transformation models with partly interval-censored data.

In many scientific fields, partly interval-censored data, which consist of exactly observed and interval-censored observations on the failure time of interest, appear frequently. However, methodological developments in the analysis of partly interval-censored data are relatively limited and have mainly focused on additive or proportional hazards models. The general linear transformation model provides a highly flexible modeling framework that includes several familiar survival models as special cases. Despite such nice features, the inference procedure for this class of models has not been developed for partly interval-censored data. We propose a fully Bayesian approach coped with efficient Markov chain Monte Carlo methods to fill this gap. A four-stage data augmentation procedure is introduced to tackle the challenges presented by the complex model and data structure. The proposed method is easy to implement and computationally attractive. The empirical performance of the proposed method is evaluated through two simulation studies, and the model is then applied to a dental health study.

The potential utilization of slag generated from iron- and steelmaking industries: a review.

Along with iron and steel production, large amount of slag is generated. Proper management on the iron- and steelmaking slag is highly demanded due to the high cost of direct disposal of the slag to landfill, which is the most adopted management approach. In this article, the potential application of iron- and steelmaking slag has been reviewed, which included the slag utilization in construction as cement and sand, in water, soil, and gas treatment, as well as in value material recovery. In addition, the challenge and required effort to be made in iron- and steelmaking slag management have been discussed.

Relationship between serum 25-hydroxyvitamin D3 levels and severity of chronic periodontitis in type 2 diabetic patients: A cross-sectional study.

BACKGROUND AND OBJECTIVES: Serum 25-hydroxyvitamin D3 (25(OH)D3 ), a newly emerged immune regulator, is considered to be involved in type 2 diabetic periodontitis (T2DCP). However, the risk factors and genes with altered expression that influence the progression and severity of T2DCP remain unknown. Accordingly, the aim of the present study was to elucidate the relationship between 25(OH)D3 deficiency and severity of T2DCP as well as the potential mechanisms. MATERIAL AND METHODS: A total of 182 subjects were divided into two groups: chronic periodontitis without diabetes (P group, n = 88) and type 2 diabetes mellitus with periodontitis (DM+P group, n = 94). Patients in both groups were further classified according to age as young (Y) and elderly (E) for a total of four groups: P/Y, P/E, DM+P/Y, and DM+P/E. Periodontal status was evaluated based on the probing depth (PD) and clinical attachment loss (CAL). The serum levels of human 25(OH)D3 , interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assays. Immunohistochemistry was used to measure the expression of protein tyrosine phosphatase non-receptor type 2 (PTPN2), vitamin D receptor (VDR), and JAK/STAT proteins in the gingival tissue. RESULTS: Serum 25(OH)D3 levels were lower in the DM+P group than those in the P group (P < 0.001). When the patients were subgrouped according to age, 25(OH)D3 deficiency was more commonly found in DM+P/E than in DM+P/Y (67% vs 51%), with a significant difference detected in the 25(OH)D3 quartile of 15-20 ng/mL (P = 0.007). The 25(OH)D3 level showed a significant negative correlation with fasting blood glucose (FBG) (r = -0.623), serum IL-1ß (r = -0.392), serum TNF-α (r = -0.218), PD (r = -0.269), and CAL (r = -0.305) in the DM+P group (all P < 0.05), but not with hemoglobin A1c (P = 0.123). Additionally, reduced VDR and PTPN2 expression levels were observed in DM+P patients, whereas JAK1 and p-STAT5 protein levels were increased in this group. CONCLUSIONS: Vitamin D3 deficiency is strongly associated with T2DCP, and age mediates this relationship. Abnormal FBG and IL-1ß levels should be considered as important potential risk factors for the progression and severity of T2DCP. Moreover, 25(OH)D3 deficiency may be related to the immune function of T2DCP by weakening PTPN2 signaling.

Relationship between circulating senescence-associated secretory phenotype levels and severity of type 2 diabetes-associated periodontitis: A cross-sectional study.

BACKGROUND: Senescence-associated secretory phenotype (SASP) has recently been found to drive comorbid diabetes and periodontitis by inducing a chronic, low-degree inflammatory state. Here, we sought to explore the relationship between circulating SASP and the severity of type 2 diabetes-associated periodontitis (DP). METHODS: Eighty patients (middle-aged periodontitis, M-P group; aged periodontitis, A-P group; M-DP group; and A-DP group; n = 20) provided gingival epithelium, serum, and periodontal clinical parameters. Circulating levels of 12 DP-related SASP factors were analyzed by immunoassay. Correlation between periodontal clinical parameters and circulating SASP levels was analyzed by Spearman's rank correlation coefficient and back propagation artificial neural network (BPNN). Senescence markers (p16, p21, and HMGB1) in gingiva were determined by immunofluorescence assay. RESULTS: M-DP group had increased serum levels of twelve SASP factors compared with the M-P group (p < 0.5). Serum levels of IL-6, IL-4, and RAGE were higher in the A-DP group than the A-P group (p < 0.5). The circulating concentrations of certain SASP proteins, including IL-1ß, IL-4, MMP-8, OPG, RANKL, and RAGE were correlated with the clinical parameters of DP. BPNN showed that serum SASP levels had considerable predictive value for CAL of DP. Additionally, the DP group had higher expressions of p16, p21, and cytoplasmic-HMGB1 in the gingiva than the P group (p < 0.5). CONCLUSIONS: Significantly enhanced circulating SASP levels and aggravated periodontal destruction were observed in patients with DP. Importantly, a non-negligible association between serum SASP levels and the severity of DP was found.

hUC-MSCs lyophilized powder loaded polysaccharide ulvan driven functional hydrogel for chronic diabetic wound healing.

In this study, we used the polysaccharide ulvan from the green macroalgae Ulva fenestrata to prepare the hydrogel for chronic diabetic wound healing. A natural polysaccharide-based hydrogel matrix (UC-DPA-Ag hydrogel) was prepared using ulvan dialdehyde, chitosan, dopamine (DPA) and silver nanoparticles (Ag NPs). Human umbilical cord mesenchymal stem cell lyophilized powder (hUC-MSCs) was loaded into the hydrogel to develop a novel chronic diabetic wound healing material (UC-DPA-Ag@hUC-MSCs). The resulting hydrogel features adequate mechanical properties, swelling capability, adhesiveness, antioxidant, antibacterial ability, and promoting cell proliferation and migration. In vivo wound healing in type II diabetic mellitus mouse wound model showed that hUC-MSCs loaded UC-DPA-Ag hydrogel could accelerate wound healing effectively. This advanced hydrogel provides a facile and effective way for diabetic chronic wound management. Furthermore, it offers a new route for the utilizing Ulva as a valuable biomaterial for the global and large-scale production of valued added biomaterials.

Unit costs for non-acute care in Ireland 2016-2019.

Background: This paper presents detailed unit costs for 16 healthcare professionals in community-based non-acute services in Ireland for the years 2016-2019. Unit costs are important data inputs for assessments of health service performance and value for money. Internationally, while some countries have an established database of unit costs for healthcare, there is need for a more coordinated approach to calculating healthcare unit costs. In Ireland, detailed cost analysis of acute care is undertaken by the Healthcare Pricing Office but to date there has been no central database of unit costs for community-based non-acute healthcare services. Methods: Unit costs for publicly employed allied healthcare professionals, Public Health Nurses and Health Care Assistant staff are calculated using a bottom-up micro-costing approach, drawing on methods outlined by the Personal Social Services Research Unit in the UK, and on available Irish and international costing guidelines. Data on salaries, working hours and other parameters are drawn from secondary datasets available from Department of Health, Health Service Executive and other public sources. Unit costs for public and private General Practitioner, dental, and long-term residential care (LTRC) are estimated drawing on available administrative and survey data. Results: The unit costs for the publicly employed non-acute healthcare professionals have changed by 2-6% over the timeframe 2016-2019 while larger percentage changes are observed in the unit costs for public GP visits and public LTRC (14-15%). Conclusions: The costs presented here are a first step towards establishing a central database of unit costs for non-acute healthcare services in Ireland. The database will help ensure consistency across Irish health costing studies and facilitate cross-study and cross-country comparisons. Future work will be required to update and expand on the range of services covered and to incorporate new data and methodological developments in cost estimation as they become available.

Salivary protease spectrum biomarkers of oral cancer.

Proteases are important molecules that are involved in many physiological and pathological processes of the human body, such as growth, apoptosis and metastasis cancer cells. They are potential targets in cancer diagnosis and biotherapy. In this study, we analyzed the salivary protease spectrum of patients with oral squamous cell carcinoma (OSCC), oral benign masses and chronic periodontitis, as well as that of health, using human protease array kits, enzyme-linked immunosorbent assay, western blot and immunofluorescence. The salivary protease spectrum was found to be associated with oral diseases. For example, the saliva of patients with OSCC contained increased numbers of proteases than those of other oral diseases and health. The levels of matrix metalloproteinase (MMP)-1, MMP-2, MMP-10, MMP-12, A disintegrin and metalloprotease (ADAM)9, A disintegrin and metalloprotease with thrombospondin type 13 motifs (ADAMST13), cathepsin V and kallikrein 5 in the saliva of patients with OSCC were significantly increased compared with those of other groups. Taking MMP-1, cathepsin V, kallikrein 5 and ADAM9 as biomarkers of OSCC, cutoff values were199, 11.34, 9.29 and 202.55 pg·mL-1, respectively. From the area under the curve, sensitivity and specificity, the combination of cathepsin V/kallikrein5/ADAM9 was an optimal biomarker for diagnosing OSCC. Thus, analysis of the salivary protease spectrum may be an innovative and cost-efficient approach to evaluating the health status of the oral cavity. Specifically, increases in cathepsin V, kallikrein 5 and ADAM9 may be useful biomarkers in the screening and diagnosis of OSCC.

Polydiacetylene liposomes with phenylboronic acid tags: a fluorescence turn-on sensor for sialic acid detection and cell-surface glycan imaging.

Sialic acid (SA) located at the terminal end of glycans on cell membranes has been shown to play an important yet distinctive role in various biological and pathological processes. Effective methods for the facile, sensitive and in situ analysis of SA on living cell surfaces are of great significance in terms of clinical diagnostics and therapeutics. Here, a new polydiacetylene (PDA) liposome-based sensor system bearing phenylboronic acid (PBA) and 1,8-naphthalimide derived fluorophore moieties was developed as a fluorescence turn-on sensor for the detection of free SA in aqueous solution and the in situ imaging of SA-terminated glycans on living cell surfaces. In the sensor system, three diacetylene monomers, PCDA-pBA, PCDA-Nap and PCDA-EA, were designed and synthesized to construct the composite PDA liposome sensor. The monomer PCDA-pBA modified with PBA molecules was employed as a receptor for SA recognition, while the monomer PCDA-Nap containing a 1,8-naphthalimide derivative fluorophore was used for fluorescence signaling. When the composite PDA liposomes were formed, the energy transfer between the fluorophore and the conjugated backbone could directly quench the fluorescence of the fluorophore. In the presence of additional SA or SA abundant cells, the strong binding of SA with PBA moieties disturbed the pendent side chain conformation, resulting in the fluorescence restoration of the fluorophore. The proposed methods realized the fluorescence turn-on detection of free SA in aqueous solution and the in situ imaging of SA on living MCF-7 cell surfaces. This work provides a new potential tool for simple and selective analysis of SA on living cell membranes.

Smart Combination of Cyclodextrin Polymer Host-Guest Recognition and Mg2+-Assistant Cyclic Cleavage Reaction for Sensitive Electrochemical Assay of Nucleic Acids.

A novel enzyme-free electrochemical sensing strategy was proposed for sensitive monitoring of DNA and miRNA by smart combination of the cyclic cleavage reaction of Mg2+-dependent DNAzyme and the host-guest inclusion between ferrocene-labeled hairpin probe (H-1) and nitrogen-doped reduced graphene oxide/ß-cyclodextrin polymer (NRGO/ß-CDP) nanocomposites. The synthesized NRGO/ß-CDP nanocomposites with high electrocatalytic activity and recognition capability were modified on the glassy carbon electrode to construct the sensing platform. Upon the hybridization reaction of subunit DNA in the loop region with target sequence, the active DNAzyme was liberated from the caged structure, which bound with H-1 to catalyze its cleavage in the presence of Mg2+ and triggered the target recycling amplification for the cleavage of a large number of H-1. Each cleaved H-1 was divided into two single-stranded oligonucleotides, leading to an obvious enhancement of peak current by the molecular recognition of ß-CDP on the electrode. Thus, the constructed biosensor showed high sensitivity and selectivity for DNA and miRNA assays, with wide concentration ranges of 0.01-1000 and 0.05-500 pM and low detection limits of 3.2 and 18 fM, respectively. This developed sensing strategy may become a promising nucleic acid detection method in bioassays and clinical diagnosis.