Prediction of hand-wrist maturation stages based on cervical vertebrae images using artificial intelligence.

OBJECTIVE: To predict the hand-wrist maturation stages based on the cervical vertebrae (CV) images, and to analyse the accuracy of the proposed algorithms. SETTINGS AND POPULATION: A total of 499 pairs of hand-wrist radiographs and lateral cephalograms of 455 orthodontic patients aged 6-18 years were used for developing the prediction model for hand-wrist skeletal maturation stages. MATERIALS AND METHODS: The hand-wrist radiographs and the lateral cephalograms were collected from two university hospitals and a paediatric dental clinic. After identifying the 13 anatomic landmarks of the CV, the width-height ratio, width-perpendicular height ratio and concavity ratio of the CV were used as the morphometric features of the CV. Patients' chronological age and sex were also included as input data. The ground truth data were the Fishman SMI based on the hand-wrist radiographs. Three specialists determined the ground truth SMI. An ensemble machine learning methods were used to predict the Fishman SMI. Five-fold cross-validation was performed. The mean absolute error (MAE), round MAE and root mean square error (RMSE) values were used to assess the performance of the final ensemble model. RESULTS: The final ensemble model consisted of eight machine learning models. The MAE, round MAE and RMSE were 0.90, 0.87 and 1.20, respectively. CONCLUSION: Prediction of hand-wrist SMI based on CV images is possible using machine learning methods. Chronological age and sex increased the prediction accuracy. An automated diagnosis of the skeletal maturation may aid as a decision-supporting tool for evaluating the optimal treatment timing for growing patients.

Thin PEGylated Carbon Nitrides: Water-Dispersible Organic Nanodots as Bioimaging Probes.

Fluorescent materials are being used for the optical/fluorescence imaging of living cells and animal models. As such, the development of heavy-metal-free, water-dispersible, and biocompatible imaging probes is still important. Carbon nitride (C3 N4 ) is used as a bioimaging probe due to its suitable optical properties, thus enhancing its biocompatibility and dispersibility in aqueous media is required. In this study, we incorporated short-chain polyethylene glycol (PEG) groups onto a carbon nitride network by the simple N-alkylation of hexaethylene glycolic mesylate with nucleophilic nitrogen atoms on oxidized carbon nitride (OCN). The PEGylated OCN (PEG-OCN) was well dispersed in water as nanodots with a lateral dimension of approximately 30 nm and a thickness of 0.5-1.2 nm and showed strong photoluminescence in the visible region. Cell-viability testing confirmed that these "heavy-metal-free" organic nanodots were highly biocompatible and noncytotoxic. In particular, the developed nanodots could provide clear confocal images of RAW 264.7 cells without weakening cell activity and displaying any aggregation in a range of concentrations (25-100 µg mL-1 ) with bright-green emission in the cytoplasm.

Thermo-responsive polymeric nanoparticles for enhancing neuronal differentiation of human induced pluripotent stem cells.

We report thermo-responsive retinoic acid (RA)-loaded poly(N-isopropylacrylamide)-co-acrylamide (PNIPAM-co-Am) nanoparticles for directing human induced pluripotent stem cell (hiPSC) fate. Fourier transform infrared spectroscopy and (1)H nuclear magnetic resonance analysis confirmed that RA was efficiently incorporated into PNIAPM-co-Am nanoparticles (PCANs). The size of PCANs dropped with increasing temperatures (300-400 nm at room temperature, 80-90 nm at 37°C) due to its phase transition from hydrophilic to hydrophobic. Due to particle shrinkage caused by this thermo-responsive property of PCANs, RA could be released from nanoparticles in the cells upon cellular uptake. Immunocytochemistry and quantitative real-time polymerase chain reaction analysis demonstrated that neuronal differentiation of hiPSC-derived neuronal precursors was enhanced after treatment with 1-2 µg/ml RA-loaded PCANs. Therefore, we propose that this PCAN could be a potentially powerful carrier for effective RA delivery to direct hiPSC fate to neuronal lineage. FROM THE CLINICAL EDITOR: The use of induced pluripotent stem cells (iPSCs) has been at the forefront of research in the field of regenerative medicine, as these cells have the potential to differentiate into various terminal cell types. In this article, the authors utilized a thermo-responsive polymer, Poly(N-isopropylacrylamide) (PNIPAM), as a delivery platform for retinoic acid. It was shown that neuronal differentiation could be enhanced in hiPSC-derived neuronal precursor cells. This method may pave a way for future treatment of neuronal diseases.

Primary ceramic-on-ceramic total hip arthroplasty using a 32-mm ceramic head with a titanium-alloy sleeve.

BACKGROUND: Modern ceramic-on-ceramic bearings have become attractive alternatives to conventional polyethylene in total hip arthroplasty (THA) as a result of their low wear and minimal particle production. However, 28-mm heads in ceramic-on-ceramic bearing couples have been associated with ceramic fracture. To address these issues, 32-mm and larger ceramic heads with a titanium-alloy sleeve have been introduced, although limited data are available on their durability and clinical outcomes. QUESTIONS/PURPOSES: We determined (1) the survivorship of the primary ceramic-on-ceramic THA using a 32-mm ceramic head with a titanium-alloy sleeve at a minimum followup of 5 years; (2) Harris hip scores; (3) the incidence of ceramic fracture and noisy hip; and (4) the proportion of hips showing radiographic evidence of osteolysis. METHODS: From November 2005 to August 2009, we performed 301 ceramic-on-ceramic THAs using a 32-mm ceramic head with a titanium-alloy sleeve in 270 patients. Of these, 12 patients (12 hips [4%]) died from problems unrelated to surgery and 13 patients (15 hips [5%]) were lost during followup before a minimum of 5 years had been reached, leaving 245 patients who had 274 THAs with a minimum followup of 5 years (mean, 6.5 years; range, 5-9 years) in this retrospective analysis. During the study period, 30% (301 of 997 hips) were performed with this articulation based on the operating surgeon's discretion. The mean patient age at the time of surgery was 55 years (range, 16-82 years). All operations were performed at a single center. All of the ceramic implants were hot isostatic-pressed, laser-marked, proof-tested third-generation alumina. We determined the implant survival, Harris hip scores, incidence of ceramic fracture or noisy hips (based on a questionnaire), and presence of osteolysis. RESULTS: The survival rate of ceramic-on-ceramic bearings in primary THA using a 32-mm ceramic head with a titanium-alloy sleeve was 98% (95% confidence interval, 96%-100%) at 9 years. The Harris hip score improved from a mean of 47 points preoperatively to 93 points at last followup. One ceramic head fractured at 6 years postoperatively. No ceramic liners fractured. Audible hip clicking and squeaking were identified in four hips and one hip, respectively. Osteolysis was detected in three hips, but none had symptoms. CONCLUSIONS: Primary ceramic-on-ceramic THA using a 32-mm ceramic head with a titanium-alloy sleeve has a survivorship of 98% at 9-year followup. Nevertheless, surgeons should be aware of the potential risks of ceramic fracture, noise, and osteolysis associated with the use of a ceramic head with a titanium-alloy sleeve. LEVEL OF EVIDENCE: Level IV, therapeutic study.

The effect of topical scar treatment on postoperative scar pain and pruritus after total knee arthroplasty.

INTRODUCTION: The surgical wound of total knee arthroplasty (TKA) needs continuous flexion and extension movement. Silicone gel treatment is widely used to treat hypertrophic scars and keloids since it is easily applied and prevents scar pain and itching. The aim of this study was to evaluate the clinical efficacy and safety of silicone gel applied to surgical scars of TKA on postoperative scar pain and pruritus. MATERIALS AND METHODS: One hundred TKAs were randomized into a silicone gel group (silicone gel was applied to the wound after stitch-out for 1 month) or a placebo group. The postoperative scar pain and pruritus were evaluated with the use of a visual analog scale (VAS) at postoperative 3 months, 6 months and 1 year. Scar assessment was done using the Vancouver scar scale by evaluating scar pigmentation, vascularity, pliability, and height. RESULTS: Although silicone gel group showed better pigmentation and height scales than placebo group (P < 0.05), there were no significant differences in the postoperative scar pain and pruritus VAS scores between the groups (P > 0.05). CONCLUSIONS: Application of silicone gel had no beneficial effects on scar pain and itching relief during the early postoperative period of TKA. LEVEL OF EVIDENCE: I-Randomized Controlled Trial.

Standardized multi-institutional data analysis of fixed and removable prosthesis: estimation of life expectancy with regards to variable risk factors.

PURPOSE: This study aims to assess and predict lifespan of dental prostheses using newly developed Korean Association of Prosthodontics (KAP) criteria through a large-scale, multi-institutional survey. MATERIALS AND METHODS: Survey was conducted including 16 institutions. Cox proportional hazards model and principal component analysis (PCA) were used to find out relevant factors and predict life expectancy. RESULTS: 1,703 fixed and 815 removable prostheses data were collected and evaluated. Statistically significant factors in fixed prosthesis failure were plaque index and material type, with a median survival of 10 to 18 years and 14 to 20 years each. In removable prosthesis, factors were national health insurance coverage, antagonist type, and prosthesis type (complete or partial denture), with median survival of 10 to 13 years, 11 to 14 years, and 10 to 15 years each. For still-usable prostheses, PCA analysis predicted an additional 3 years in fixed and 4.8 years in removable prosthesis. CONCLUSION: Life expectancy of a prosthesis differed significantly by factors mostly controllable either by dentist or a patient. Overall life expectancy was shown to be longer than previous research.

Mucosal Penetrative Polymeric Micelle Formulations for Insulin Delivery to the Respiratory Tract.

Purpose: Effective mucosal delivery of drugs continues to pose a significant challenge owing to the formidable barrier presented by the respiratory tract mucus, which efficiently traps and clears foreign particulates. The surface characteristics of micelles dictate their ability to penetrate the respiratory tract mucus. In this study, polymeric micelles loaded with insulin (INS) were modified using mucus-penetrative polymers. Methods: We prepared and compared polyethylene glycol (PEG)-coated micelles with micelles where cell-penetrating peptide (CPP) is conjugated to PEG. Systematic investigations of the physicochemical and aerosolization properties, performance, in vitro release, mucus and cell penetration, lung function, and pharmacokinetics/pharmacodynamics (PK/PD) of polymeric micelles were performed to evaluate their interaction with the respiratory tract. Results: The nano-micelles, with a particle size of <100 nm, exhibited a sustained-release profile. Interestingly, PEG-coated micelles exhibited higher diffusion and deeper penetration across the mucus layer. In addition, CPP-modified micelles showed enhanced in vitro cell penetration. Finally, in the PK/PD studies, the micellar solution demonstrated higher maximum concentration (Cmax) and AUC0-8h values than subcutaneously administered INS solution, along with a sustained blood glucose-lowering effect that lasted for more than 8 h. Conclusion: This study proposes the use of mucus-penetrating micelle formulations as prospective inhalation nano-carriers capable of efficiently transporting peptides to the respiratory tract.

Survivorship of implanted bone marrow-derived mesenchymal stem cells in acute rotator cuff tear.

BACKGROUND: This study examined whether a mesenchymal stem cells (MSCs)-seeded 3-dimensional construct into a tendon defect would promote cellular differentiation and matrix healing. MATERIALS AND METHODS: Bone marrow was harvested from the iliac crests of 2 male New Zealand White rabbits. The MSCs were cultured, and an open-cell polylactic acid (OPLA) scaffold was encapsulated with these cells. The injury model was a 5-mm × 5-mm-sized full-thickness window defect in the central part of each rotator cuff tendon. The defects on the right side were grafted with the autologous MSCs-seeded OPLA scaffold implant and a biodegradable suture. The same procedure was done on the left side, except a cell-free OPLA scaffold was used. Three rabbits were used as controls, without treatment of the tendon defect. Samples were harvested at 2, 4, and 6 weeks for analysis, which included evaluation of gross morphology, fluorescent analysis, histologic assessment, and immunohistochemistry studies. RESULTS: The expression of immunohistochemical stainings for collagen I was higher in the scaffold with MSCs than in the scaffold without MSCs. The expression of collagen II, however, was not different between the scaffolds with and without MSCs. CONCLUSIONS: Even though this is a short-term study, we demonstrated that many MSCs in the scaffold survived after implantation in an acute rabbit rotator cuff defect. Furthermore, the generation of type I collagen increased more in the scaffold with MSCs than it did in the scaffold without MSCs. MSCs are thought to promote tendon healing by producing type I collagen when they are applied at the tendon defect.

The Use of Phentermine for Obesity in Psychiatric Patients With Antipsychotics.

OBJECTIVE: Phentermine is a commonly used weight-loss agent in the United States, but there is a little information about the use of phentermine for patients with obesity taking antipsychotic medications. METHODS: We gathered 57 patients with obesity taking antipsychotic medications whose phentermine treatment was simultaneous with or after any type of antipsychotic exposure and collected data of clinical information, initial/follow-up anthropometric variables, and adverse events (AEs) for the 6-month study period. RESULTS: In total, the mean body weight reduction (BWR) was 4.45 (7.04) kg, and the mean BWR percent (BWR%) was 3.92% (6.96%) at 6 months. Based on the response to phentermine, the patients were classified into two groups: the responder (n=25; BWR% ≥5%) and nonresponder (n=32; BWR% <5%) groups. The responder group's mean BWR and BWR% were 10.13 (4.43) kg and 9.35% (4.09%), respectively, at 6 months. The responders had higher rates of anticonvulsant combination therapy (ACT; responder, 72.0% vs. non-responder, 43.8%; p=0.033) and a shorter total antipsychotic exposure duration (responder, 23.9 [16.9] months vs. non-responder, 37.2 [27.6] months; p= 0.039). After adjusting age, sex, and initial body weight, ACT maintained a significant association with phentermine response (odds ratio=3.840; 95% confidence interval: 1.082-13.630; p=0.037). In the final cohort, there was no report of adverse or new-onset psychotic symptoms, and the common AEs were sleep disturbances, dry mouth, and dizziness. CONCLUSION: Overall, phentermine was effective and tolerable for patients with obesity taking antipsychotic medications, and ACT (predominantly topiramate) augmented the weight-loss effect of phentermine.

Design and Optimization of Rivaroxaban-Cyclodextrin-Polymer Triple Complex Formulation with Improved Solubility.

Purpose: This study aimed to ensure the convenience of administration and reproducibility of efficacy, regardless of the meal, by improving the solubility of rivaroxaban (RIV). Methods: RIV is a non-vitamin K antagonist oral anticoagulants that exhibits a coagulation effect by directly inhibiting coagulation factor Xa. However, RIV has a very low solubility; therefore, it must be administered with a meal at high doses. We used a drug- hydroxypropyl-beta-cyclodextrin (CD)-water-soluble polymer triple complex (R-C-P complex) to solubilize RIV. Using Minitab, we evaluated the effect of each factor on RIV solubility and developed an optimal R-C-P complex formulation. The amount of CD, amount of polymer, and polymer type were set as the independent variables X1, X2, and X3, respectively. RIV solubility (Y1) and dissolution rate for 45 min in pH 4.5 medium (Y2) and pH 1.2 medium (Y3) were set as response variables. Results: The most efficient RIV solubilization effect was obtained from the composition using CD and HPMC 2208, and physicochemical properties and dissolution parameters were analyzed. RIV in the R-C-P complex was present in an amorphous form and showed high solubility. Unlike commercial products, it showed a 100% dissolution rate. The R-C-P complex formulation secured high RIV solubility and 100% release regardless of pH. Conclusion: The results imply that high-dose RIV can be administered regardless of the meal, reducing the risk of changing the drug effect due to the patient's administration mistake.

Influence of hydrophilic polymers on mechanical property and wound recovery of hybrid bilayer wound dressing system for delivering thermally unstable probiotic.

In this study, a novel hybrid bilayer wound dressing (HBD) has been developed for delivering a thermally unstable probiotic, Lactobacillus brevis. The HBD was composed of two layer, a hydrocolloid layer and a Lactobacillus brevis-loaded hydrogel layer as a block supporter and drug carrier, respectively. Moreover, various probiotic-loaded hydrogel layers in HBD were prepared with polyvinyl alcohol (PVA) and numerous hydrophilic polymers via a freezing and thawing method, and their mechanical property, release and wound recovery were assessed. Among the hydrophilic polymers investigated, copovidone most improved the mechanical strength, swelling ability, and release properties; and thus, copovidone/PVA (ratio of 1.0/10) was determined as an appropriate composition of hydrogel layer in HBD. The selected HBD exhibited superior stability than conventional dressing, maintaining approximately 90% of Lactobacillus brevis (9.0 × 108 CFU) during the preparation and storage process. Moreover, the HBD had about 5- and 4-fold better swelling ability and elasticity compared to the conventional dressing. Additionally, it exhibited superior recovery efficacy than the commercial dressing in the animal study. Therefore, this HBD system for delivering a thermally unstable Lactobacillus brevis would be a promising wound dressing with excellent mechanical property and wound recovery.

Risk Factors of Microscopically Tumor-Free Surgical Margins for Recurrence and Survival of Oral Squamous Cell Carcinoma Patients.

Objectives: The concept of adequate surgical margins remains controversial in oral squamous cell carcinoma (OSCC) surgery. This study aimed to identify surgical margin-related indicators that might impact recurrence and survival of OSCC patients. Materials and Methods: Histopathological examination was performed using hematoxylin-eosin-stained surgical margin tissue sections in 235 OSCC patients. Axin2 and Snail expression at the surgical margin was detected by immunohistochemistry. The impact of the Axin2-Snail cascade on tumorigenesis of the immortalized human oral keratinocyte (IHOK) line was investigated in vivo. Results: The width and dysplasia of surgical margins were not significantly associated with the outcome of OSCC patients. In a multivariate analysis using variable clinicopathologic factors and with Axin2 and Snail expression as cofactors, higher age (hazard ratio [HR]:1.050; P=0.047), Axin2 (HR:6.883; P=0.014), and Snail abundance (HR:5.663; P=0.009) had independent impacts on worsened overall survival. Similarly, lesion site in retromolar trigone (HR:4.077; P=0.010), upper (HR:4.332; P=0.005) and lower gingiva (HR:3.545; P=0.012), presence of extranodal extension (HR:9.967; P<0.001), perineural invasion (HR:3.627; P=0.024), and Snail abundance (HR:3.587; P<0.001) had independent impacts on worsened recurrence-free survival. Furthermore, Axin2 knockdown induced decreased Snail expression and attenuated tumorigenesis in the IHOK line. Conclusion: Histopathological examination of surgical margins may not be reliable to predict OSCC patient outcome. Molecular analysis may provide a more accurate risk assessment of surgical margins in OSCC. In particular, Axin2 and Snail are potential predictive biomarkers for the risk assessment of surgical margins in OSCC.

Effect of artifact area on cone beam computed tomography scans when integrated with intraoral scans.

OBJECTIVE: The aim of this study was to examine whether integration accuracy increases upon removing artifacts from the registration area when integrating maxillofacial cone beam computed tomography (CBCT) scans and intraoral scans. STUDY DESIGN: Three methods were implemented according to the region of interest (ROI): R0, all teeth included as the registration area (artifacts included); R1, anterior teeth included as the registration area (artifacts in premolars and molars not included); and R2, anterior teeth and second molars included as the registration area (artifacts in premolars and first molars not included). Discrepancies between the 2 images were evaluated by using color-mapping methods. The average surface distance was calculated by measuring the shell/shell deviations for overall discrepancies and 3-dimensional distances between the surface points on the 2 images for registration discrepancies. RESULTS: The R1 method showed more discrepancies between the CBCT and intraoral scans compared with the other 2 methods. The R2 method showed smaller overall discrepancy values compared with the R1 method. Most CBCT artifacts were located in the posterior area. Registration discrepancies were greatest in the x-dimension. CONCLUSIONS: The results suggest that intraoral and CBCT scans might be integrated by using a registration method that involves exclusion of artifacts and inclusion of the second molar on both sides.

Carbon-ion radiotherapy in osteosarcoma of the mandible: a case report.

Carbon-ion radiotherapy (CIRT) is on the rise as a treatment choice for malignant tumor. Compared to conventional radiotherapy, particle beams have different physical and biological properties. Particle beam provides a low entry dose, deposits most of the energy at the endpoint of the flight path, and forms an asymptotic dose peak (the "Bragg peak"). Compared to protons, carbon with its larger mass decreases beam scattering, resulting in a sharper dose distribution border. We report a 50-year-old male who underwent CIRT without surgical resection on osteosarcoma of the mandible. After CIRT, the patient's pain was gone, and the malignant mass remained stable with accompanying necrosis. Nine months later, however, magnetic resonance imaging demonstrated progression of the left mandibular osteosarcoma with pulmonary metastases. After multidisciplinary discussion, concurrent chemoradiotherapy was conducted. While necrotic bone segments came out of the mandible during subsequent periodic outpatient visits, the tumor itself was stable. Thirty months after his first visit and diagnosis, the patient is waiting for chemotherapy. Although CIRT is superior in treating radioresistant hypoxic disease, CIRT is in its infancy, so care must be taken for its indications and complications.

Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses.

BACKGROUND: Immunization with the spike protein (S) of severe acute respiratory syndrome (SARS)-coronavirus (CoV) in mice is known to produce neutralizing antibodies and to prevent the infection caused by SARS-CoV. Polyethylenimine 25K (PEI) is a cationic polymer which effectively delivers the plasmid DNA. RESULTS: In the present study, the immune responses of BALB/c mice immunized via intranasal (i.n.) route with SARS DNA vaccine (pci-S) in a PEI/pci-S complex form have been examined. The size of the PEI/pci-S nanoparticles appeared to be around 194.7 ± 99.3 nm, and the expression of the S mRNA and protein was confirmed in vitro. The mice immunized with i.n. PEI/pci-S nanoparticles produced significantly (P < 0.05) higher S-specific IgG1 in the sera and mucosal secretory IgA in the lung wash than those in mice treated with pci-S alone. Compared to those in mice challenged with pci-S alone, the number of B220+ cells found in PEI/pci-S vaccinated mice was elevated. Co-stimulatory molecules (CD80 and CD86) and class II major histocompatibility complex molecules (I-Ad) were increased on CD11c+ dendritic cells in cervical lymph node from the mice after PEI/pci-S vaccination. The percentage of IFN-γ-, TNF-α- and IL-2-producing cells were higher in PEI/pci-S vaccinated mice than in control mice. CONCLUSION: These results showed that intranasal immunization with PEI/pci-S nanoparticles induce antigen specific humoral and cellular immune responses.

Prognostic value of systemic inflammatory markers for oral cancer patients based on the 8th edition of AJCC staging system.

It has been recognized that systemic inflammatory markers (SIMs) are associated with patient survival in various types of cancer. This study aimed to determine the optimal cut-off values, and to evaluate the prognostic performance of SIMs for oral squamous cell carcinoma (OSCC) within the framework of the American Joint Committee of Cancer (AJCC) cancer staging manual, 8th edition. Records were collected for a total 291 patients who had had a peripheral blood test within 1 week prior to surgery and had undergone the surgical resection of OSCC in a single institution between 2005 and 2018. The cut-off values of SIMs were obtained, and the survival analyses for overall survival (OS) and disease-free survival (DFS) were performed. Multivariate analyses incorporating other clinicopathologic factors were performed to verify the independent risk factors for survival. The cut-off values of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were 2.23, 135.14 for OS and 2.16, 131.07 for DFS, respectively, demonstrating a significant association for OS and DFS in OSCC. AJCC pathologic regional lymph node category (pN) (P < 0.001), perineural invasion (PNI) (P < 0.001) and NLR (P < 0.001) were independent predictors for OS. Meanwhile, for DFS, AJCC pN (P = 0.018) and NLR (P = 0.015) were shown to be independent predictors. Before the curative surgery, NLR and PLR could be auxiliary parameters for OS and DFS in OSCC. And based on the 8th edition of AJCC staging system, elevated NLR will be a potential indicator of the worse OS or DFS along with pN or PNI in OSCC.

Production, characterization, and evaluation of two types of slow-releasing carbon source tablets for in-situ heterotrophic nitrate denitrification in aquifers.

Slow-releasing carbon source tablets were manufactured for an in-situ biological denitrification system. The average zero-order nitrate degradation rates seen, from highest to lowest, were in microcosms to which lactate, fumarate, propionate, and formate had been added. Fumarate was approximately 80% cheaper than lactate, and consequently was determined to be the most optimal slow-releasing carbon source in tablet form. The slow-releasing precipitating tablet (SRPT) and slow-releasing floating tablet (SRFT) were manufactured with hydroxypropyl methylcellulose (HPMC) as the agent of release control, microcrystalline cellulose pH 101 (MCC 101) as the binder, #8 sand as the precipitation agent, and calcium carbonate and citric acid as floating agents. Fourier transform infrared spectroscopy and powder X-ray diffraction indicated that the crystal arrangement in the SRPTs and SRFTs was maintained and ordered in a manner similar to raw excipients. SRFTs floated in water within 30 min and remained so for 5 d due to the buoyancy of carbon dioxide. The carbon source release rate was proportional to the quantity of HPMC added. The longevities of SRPT with 300 mg of HPMC and SRFT with 400 mg of HPMC were 25.4 d and 37.3 d, respectively. This study observed that SRPT and SRFT were manufactured effectively and are suitable for in-situ slow-releasing biological systems.

Fe3O4@Void@Microporous Organic Polymer-Based Multifunctional Drug Delivery Systems: Targeting, Imaging, and Magneto-Thermal Behaviors.

Multifunctional drug delivery systems were designed and engineered by template synthesis of a microporous organic polymer (MOP) and by postsynthetic modification. Hollow MOP spheres bearing Fe3O4 yolks (Fe3O4@Void@MOP) were prepared by the synthesis of MOP on Fe3O4@SiO2 nanoparticles and by successive silica etching. In addition to the magneto-thermal function of Fe3O4 yolks, an aggregation-induced emission (AIE) feature was incorporated into the Fe3O4@Void@MOP through a homocoupling of tetra(4-ethynylphenyl)ethylene to form Fe3O4@Void@MOP-TE. Folate groups were further introduced into Fe3O4@Void@MOP-TE through the postsynthetic modification based on the thiol-yne click reaction. The resultant Fe3O4@Void@MOP-TE-FA showed multifunctionality in antitumoral therapy via folate receptor targeting, doxorubicin delivery, AIE-based imaging, and the magneto-thermal feature.

Prognostic Implications of Combined Imaging and Histologic Criteria in Squamous Cell Carcinoma with Mandibular Invasion.

Prognosis prediction of squamous cell carcinoma (SCC) with mandibular invasion is controversial, and a more sophisticated staging system to aid prognosis could be developed with imaging characteristics of bone invasion. Imaging-feature analysis provides practical, stratified results for survival prognosis in oral SCC (OSCC) of the mandible, and imaging advances enable more detailed tumor visualization. We retrospectively evaluated significant bone-invasion features associated with poor outcomes in mandibular OSCC to assess the predictive value of staging criteria that combined imaging features and histologic grade (combined imaging-histology (IH) grade) in 65 patients (39 men, 26 women) with mandibular SCC diagnosed from 2006 to 2016. Clinicopathologic features, including T-stage and histologic grade, and prognosis were retrieved. Tumors were classified into three types by extent of mandibular invasion on pretreatment imaging studies. Moreover, we assessed the involvement of the mandibular canal. We examined the correlation of factors associated with locoregional recurrence and overall mortality. The Harrell Concordance Index (C-index) determined prognostic performance of predictors. Nineteen (29%) patients showed locoregional recurrence and 13 (20%) died. For locoregional recurrence and mortality rates, imaging-detected mandibular canal (MC) involvement is a stronger prognostic factor for recurrence (C-index = 0.61 > 0.58) and survival (C-index = 0.58 > 0.63) than histopathologically confirmed perineural invasion, as was the IH grade, especially IH Grade 3, which was significantly associated with worse locoregional recurrence (p < 0.02). Imaging-based staging showed higher prognostic performance than T-staging (C-index = 0.57 (recurrence), 0.60 (death)), when combined with histologic grading (C-index = 0.69 for both) or used alone (C-index = 0.63 (locoregional recurrence), 0.69 (death)). Overall survival was significantly stratified by Imaging type and IH grade. Therefore, analysis of imaging features provided more specific, practical results for survival prognosis in mandibular OSCC. Imaging advances can potentially provide detailed gross views of tumor masses to facilitate development of prognostic criteria for OSCC.

Development of novel mucoadhesive pellets of metformin hydrochloride.

Mucoadhesive polymer-coated pellets containing metformin hydrochloride were prepared by the powder-layering technique using a centrifugal fluidizing (CF)-granulator. Four high-viscosity polymers were applied to make the pellets: 1) hydroxymethylcellulose (HPMC), 2) sodium alginate (Na-Alg), 3) HPMC/Carbopol, and 4) sodium carboxylmethylcellulose (Na-CMC). The physical crushing test, mucoadhesive test, zeta-potential test, in vitro release study and observation of gastroretention state of the dosage form were performed to investigate the pellets. The strong adhesive interaction between the Na-CMC-coated pellets and the mucin disc was obtained by mucoadhesive test. Na-Alg was most effective among the polymers used in changing the value of zeta potential of the mucin solution by the interaction between a polymer and a mucin particle. Results from drug dissolution study showed that over 95% of the drug from all the four pellets was released before 2 h, while Na-CMC- and Na-Alg-coated pellets showed a moderate sustained-release in SGF (simulated gastric fluid) and SIF (simulated intestine fluid), respectively. In conclusion, Na-CMC and Na-Alg seem to be promising candidates for mucoadhesive formulation and further studies to improve the sustained-release property are underway for achieving the ultimate goal of once-a-day formulation of metformin hydrochloride.