Synthesis of Room Temperature Curable Polymer Binder Mixed with Polymethyl Methacrylate and Urethane Acrylate for High-Strength and Improved Transparency.

Urethane acrylate (UA) was synthesized from various di-polyols, such as poly(tetrahydrofuran) (PTMG, Mn = 1000), poly(ethylene glycol) (PEG, Mn = 1000), and poly(propylene glycol) (PPG, Mn = 1000), for use as a polymer binder for paint. Polymethyl methacrylate (PMMA) and UA were blended to form an acrylic resin with high transmittance and stress-strain curve. When PMMA was blended with UA, a network structure was formed due to physical entanglement between the two polymers, increasing the mechanical properties. UA was synthesized by forming a prepolymer using di-polyol and hexamethylene diisocyanate, which were chain structure monomers, and capping them with 2-hydroxyethyl methacrylate to provide an acryl group. Fourier transform infrared spectroscopy was used to observe the changes in functional groups, and gel permeation chromatography was used to confirm that the three series showed similar molecular weight and PDI values. The yellowing phenomenon that appears mainly in the curing reaction of the polymer binder was solved, and the mechanical properties according to the effects of the polyol used in the main chain were compared. The content of the blended UA was quantified using ultravioletvisible spectroscopy at a wavelength of 370 nm based on 5, 10, 15, and 20 wt%, and the shear strength and tensile strength were evaluated using specimens in a suitable mode. The ratio for producing the polymer binder was optimized. The mechanical properties of the polymer binder with 5-10 wt% UA were improved in all series.

Synthesis of a Room-Temperature Curable Acrylic-Urethane Polymer Binder for Road Markings with High Transmittance.

Triol acrylic-urethane (t-AU) was synthesized from an addition reaction using trimethylolpropane, hexamethylene diisocyanate, and 2-hydroxyethyl methacrylate. The novel acrylic-urethane polymer was applied to a high-performance binder to prepare a reliable road marking paint. Acrylic-urethane polymer binder formulations were designed to optimize the effect of t-AU on the physical properties. The t-AU content in the formulation affected the adhesion and optical properties. The improvement in the adhesive performance and transparency ability for road markings was attributed to the optimal chemical structure or design of the acrylic-urethane polymer. The synthesis of t-AU was confirmed by Fourier transform infrared spectroscopy, and molecular weight and polydispersity index (PDI; PDI = Mw/Mn) measurements. The tensile and shear strength, hardness, gel fraction, crosslink density, contact angle, and transmittance of the acrylic-urethane polymer binder (AUP) were evaluated by curing at room temperature using a redox initiator system. An optimized AUP by adding 5 wt.% t-AU provides a viable alternative to high-performance binders in road marking paints.

Melatonin protects against cadmium-induced oxidative stress via mitochondrial STAT3 signaling in human prostate stromal cells.

Melatonin protects against Cadmium (Cd)-induced toxicity, a ubiquitous environmental toxicant that causes adverse health effects by increasing reactive oxygen species (ROS) production and mitochondrial dysfunction. However, the underlying mechanism remains unclear. Here, we demonstrate that Cd exposure reduces the levels of mitochondrially-localized signal transducer and activator of transcription 3 (mitoSTAT3) using human prostate stromal cells and mouse embryonic fibroblasts. Melatonin enhances mitoSTAT3 abundance following Cd exposure, which is required to attenuate ROS damage, mitochondrial dysfunction, and cell death caused by Cd exposure. Moreover, melatonin increases mitochondrial levels of GRIM-19, an electron transport chain component that mediates STAT3 import into mitochondria, which are downregulated by Cd. In vivo, melatonin reverses the reduced size of mouse prostate tissue and levels of mitoSTAT3 and GRIM-19 induced by Cd exposure. Together, these data suggest that melatonin regulates mitoSTAT3 function to prevent Cd-induced cytotoxicity and could preserve mitochondrial function during Cd-induced stress.

Synchrony of biomarker variability indicates a critical transition: Application to mortality prediction in hemodialysis.

Critical transition theory suggests that complex systems should experience increased temporal variability just before abrupt state changes. We tested this hypothesis in 763 patients on long-term hemodialysis, using 11 biomarkers collected every two weeks and all-cause mortality as a proxy for critical transitions. We find that variability-measured by coefficients of variation (CVs)-increases before death for all 11 clinical biomarkers, and is strikingly synchronized across all biomarkers: the first axis of a principal component analysis on all CVs explains 49% of the variance. This axis then generates powerful predictions of mortality (HR95 = 9.7, p < 0.0001, where HR95 is a scale-invariant metric of hazard ratio; AUC up to 0.82) and starts to increase markedly ∼3 months prior to death. Our results provide an early warning sign of physiological collapse and, more broadly, a quantification of joint system dynamics that opens questions of how system modularity may break down before critical transitions.

Transparency- and Repellency-Enhanced Acrylic-Based Binder for Stimuli-Responsive Road Paint Safety Improvement Technology.

In the current study, an acrylic polymer binder applicable to road signs was successfully developed by mixing various acrylic, acrylate-type, and photoinitiator-based monomer species at different acrylate series/silicone acrylate ratios. An amorphous acrylic monomer was used, and the distance between the polymers was increased to improve transparency. The binder was designed with the purpose of reducing the yellowing phenomenon due to resonance by excluding the aromatic ring structure, which is the main cause of yellowing. The optical properties of the binder were determined according to the content of n-butyl methacrylate/methyl methacrylate and the composition of the crosslinking agent in the formulation. Allyl glycidyl ether and dilauroyl peroxide were used to improve the yellowing problem of benzoyl peroxide, an aromatic photoinitiator. Adding a silicone-based trivalent acrylic monomer, 3-(trimethoxysilyl)propyl methacrylate (TMSPMA), was also found to have a significant effect on the transparency, shear properties, and water resistance of the binder. When 15 wt% TMSPMA was added, the best water repellency and mechanical properties were exhibited. The surface morphology of the improved binder and the peeling part were confirmed using field emission scanning electron microscopy. The acrylic polymer developed in this study can be applied in the coating and adhesive industries.

Tacky-Free Polyurethanes Pressure-Sensitive Adhesives by Molecular-Weight and HDI Trimer Design.

Polyurethane pressure-sensitive adhesives (PU-PSAs) with satisfactory tack, cohesion, and removability were newly developed through the synthetic process by reacting methylene diisocyanate, poly(ethylene glycol) (PEG), and a 1,4-butanediol chain extender based on the different HDI/HDI trimer ratios. The sticking properties of PU-PSAs depended on both the HDI/HDI trimer ratio and crosslinking-agent composition in the formulation. The molecular weight (MW) dependence of adhesion in PU-PSA was observed in the range of 1000 < Mn < 3000, suggesting that the increase in MW limits the pressure-sensitive adhesion of these samples. The differences in the crosslinking-density significantly affected the cohesion, adhesion, and tack in PU-PSA. The formulation of 50 wt.% 600PEG and 50 wt.% crosslinking-agent and an HDI/HDI trimer ratio of 1.0 led to the optimal balance between the adhesion and cohesion properties owing to the sufficient tack, high 180-peel strength, and good cohesion.

Is there a difference in joint line restoration in revision Total knee arthroplasty according to prosthesis type?

BACKGROUND: The aim of this study is (1) to compare joint line (JL) restoration and clinical outcomes in revision TKA based on the contemporary prosthesis type and (2) to determine the restoration of posterior condylar offset (PCO) according to the use of a femoral offset stem. METHODS: Sixty knees that underwent revision TKA from April 2003 to December 2013 with a minimum of 1 year follow up were included. These were further subdivided into three groups according to prosthesis type: group I (2 mm offset), group II (4.5 mm offset), group III (2, 4, and 6 mm offset). The JL position change was defined as a change in the adductor tubercle distance, preoperatively versus postoperatively. We also collected the change of PCO in distal femur and clinical outcomes including range of motion (ROM) and knee scores at the preoperative and last follow-up periods. RESULTS: The JL elevation for group III was significantly lower than that of the other groups. Usage of the tibial and femoral offset stem in group III was more frequent than in the other groups. PCO in revision TKA with a femoral offset stem was significantly greater than in those with a femoral straight stem. The JL position in revision TKA with a femoral offset stem was less elevated than in those with a femoral straight stem. CONCLUSIONS: More recent developed revision prosthesis with various sizes option of offset stem may be effective in restoring the native joint line as using the femoral offset stem more convenience in revision TKAs.

A Multicenter, Double-Blind, Phase III Clinical Trial to Evaluate the Efficacy and Safety of a Cell and Gene Therapy in Knee Osteoarthritis Patients.

The aim of this study was to test the clinical efficacy of TissueGene-C (TG-C), a cell and gene therapeutic for osteoarthritis consisting of non-transformed and transduced chondrocytes (3:1) retrovirally transduced to overexpress transforming growth factor-ß1. A total of 163 Kellgren-Lawrence grade 3 patients with knee osteoarthritis were randomly assigned to receive intra-articular TG-C or placebo. Primary efficacy measures included criteria for subjective assessment by International Knee Documentation Committee (IKDC) and pain severity by Visual Analog Scale (VAS) for 52 weeks. Secondary efficacy measures included IKDC and VAS at 26 and 39 weeks; pain, stiffness, and physical function by the Western Ontario and McMaster Universities Arthritis Index (WOMAC); and pain, symptoms, daily activities, function in sports and recreation, and quality of life by the Knee Injury and Osteoarthritis Outcome Score (KOOS), X-ray, magnetic resonance imaging, and soluble urine and blood biomarkers. TG-C was associated with statistically significant improvement over placebo in the total IKDC score and individual categories, and in the VAS score at 26, 39, and 52 weeks. WOMAC and KOOS scores also improved with TG-C over placebo. Patients treated with TG-C showed trends directed toward thicker cartilage and slower growing rates of subchondral bone surface area in the medial tibia, lateral tibia, lateral patella, and lateral patella femoral regions, although these were not statistically significant (p > 0.05). Serum C-terminal telopeptide of type I collagen (CTX-I) and urine CTX-II levels were lower over 1 year in TG-C than placebo-treated patients, with CTX-I level reaching statistical significance. These tendencies supported TG-C as holding great potential as a disease-modifying osteoarthritis drug. The most frequent adverse events in the TG-C group were peripheral edema (9%), arthralgia (8%), joint swelling (6%), and injection site pain (5%). TG-C was associated with statistically significant improvements in function and pain in patients with knee osteoarthritis. The unexpected adverse events were not observed.

Safety and efficacy of bi-annual intra-articular LBSA0103 injections in patients with knee osteoarthritis.

The objective of this study is to assess the safety and efficacy of repeated intra-articular injection of high molecular weight hyaluronic acid (LBSA0103) at a 26-week interval, in patients with osteoarthritis of the knee. The study was an open-label, single arm, multicentre prospective trial conducted in patients with symptomatic knee osteoarthritis. The intervention consisted of two intra-articular injections of LBSA0103, with the second injection performed 26 weeks after the first injection. The primary outcome was the incidence of adverse drug reactions related to each injection. Assessment of efficacy of repeated injections in terms of maintenance of pain relief was a secondary objective of this study. Of the 185 patients screened, 174 patients received the first injection and 153 patients received both injections of LBSA0103. Nine adverse drug reactions occurred in seven patients (4.02%) after the first injection, while only one adverse drug reaction occurred (0.65%) after the second injection. As a secondary outcome measure, the improvements in the efficacy parameters including total WOMAC score and weight-bearing pain were all significant at both week 13 and 39 compared to the baseline value (P < 0.001), and improvements after the second injection were consistent with those after the initial injection of LBSA0103 (between week 26 and week 39, P < 0.001). Repeated intra-articular injection of LBSA0103 at a 26-week interval is safe without increased risk of adverse drug reactions. Additionally, LBSA0103 is effective in reduction of osteoarthritis knee pain and in maintenance of pain reduction for a 39-week period when a second injection is administered.

Efficacy and safety of single injection of cross-linked sodium hyaluronate vs. three injections of high molecular weight sodium hyaluronate for osteoarthritis of the knee: a double-blind, randomized, multi-center, non-inferiority study.

BACKGROUND: This randomized, double-blind, multi-center, non-inferiority trial was conducted to assess the efficacy and safety of a cross-linked hyaluronate (XLHA, single injection form) compared with a linear high molecular hyaluronate (HMWHA, thrice injection form) in patients with symptomatic knee osteoarthritis. METHODS: Two hundred eighty seven patients with osteoarthritis (Kellgren-Lawrence grade I to III) were randomized to each group. Three weekly injections were given in both groups but two times of saline injections preceded XLHA injection to maintain double-blindness. Primary endpoint was the change of weight-bearing pain (WBP) at 12 weeks after the last injection. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis index; patient's and investigator's global assessment; pain at rest, at night, or in motion; OMERACT-OARSI responder rate; proportion of patients achieving at least 20 mm or 40% decrease in WBP; and rate of rescue medicine use and its total consumption. RESULTS: Mean changes of WBP at 12 weeks after the last injection were -33.3 mm with XLHA and -29.2 mm with HMWHA, proving non-inferiority of XLHA to HMWHA as the lower bound of 95% CI (-1.9 mm, 10.1 mm) was well above the predefined margin (-10 mm). There were no significant between-group differences in all secondary endpoints. Injection site pain was the most common adverse event and no remarkable safety issue was identified. CONCLUSIONS: This study demonstrated that a single injection of XLHA was non-inferior to three weekly injections of HMWHA in terms of WBP reduction, and supports XLHA as an effective and safe treatment for knee osteoarthritis. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01510535 ). This trial was registered on January 6, 2012.

Gastrointestinal safety and efficacy of long-term GCSB-5 use in patients with osteoarthritis: A 24-week, multicenter study.

ETHNOPHARMACOLOGY RELEVANCE: A previous study indicated non-inferiority of GCSB-5 to celecoxib regarding efficacy and safety in treating OA; however, the gastrointestinal (GI) safety data was limited to 12 weeks. Accordingly, a longer term study with a larger number of patients was necessary to establish the GI safety of GCSB-5. AIM OF STUDY: The primary goal was to determine the safety and efficacy of 24-week use of GCSB-5. The secondary goal was to compare the GI safety data of GCSB-5 with that of the previously reported Celecoxib Long-term Arthritis Safety Study (CLASS). METHOD: This was a 24-week, multicenter, single-arm phase IV Study for the safety and efficacy of GCSB-5. A total of 761 patients were enrolled and 756 patients received at least one dose of GCSB-5. Among them, 629 patients (82.7%) completed the 24 week follow up. The primary goal was to determine the safety and efficacy of GCSB-5 for 24 weeks. The secondary goal was to compare the GI safety data of GCSB-5 with that of the previously reported Celecoxib Long-term Arthritis Safety Study (CLASS). RESULTS: The incidence of GI disorders of GCSB-5 was 23.7%. The annual rate of perforation, ulcer obstruction, or bleeding (PUB) incidence was 0.0%. The drop-out rate due to GI disorders following GCSB-5 use was 4.8%. Compared to celecoxib data from CLASS, the incidence of GI disorders (23.7% vs. 31.4%, p<0.001), annual rate of PUB and gastroduodenal ulcers (0.0% vs 2.2%, p=0.004), and drop-out rate due to GI disorders following GCSB-5 use were significantly low (4.8% vs 8.7%, p<0.001). Efficacy was proven by significant improvements in Western Ontario McMaster Questionnaire (WOMAC) scale, Korean Knee Score (KKS), 100-mm pain visual analogue scale (VAS), and physician's global assessments of patient's response to therapy (PGART). CONCLUSIONS: The safety and efficacy profile of GCSB-5 are comparable to celecoxib. These results indicate GCSB-5 is safe for a long-term treatment of knee OA patients. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01604239).

A randomized study to compare the efficacy and safety of extended-release and immediate-release tramadol HCl/acetaminophen in patients with acute pain following total knee replacement.

OBJECTIVE: To evaluate the relative efficacy and safety of extended-release tramadol HCl 75 mg/acetaminophen 650 mg (TA-ER) and immediate-release tramadol HCl 37.5 mg/acetaminophen 325 mg (TA-IR) for the treatment of moderate to severe acute pain following total knee replacement. METHODS: This phase III, double-blind, placebo-controlled, parallel-group study randomized 320 patients with moderate to severe pain (≥4 intensity on an 11 point numeric rating scale) following total knee replacement arthroplasty to receive oral TA-ER (every 12 hours) or TA-IR (every 6 hours) over a period of 48 hours. In the primary analysis, TA-ER was evaluated for efficacy non-inferior to that of TA-IR based on the sum of pain intensity difference (SPID) at 48 hours after the first dose of study drug (SPID48). Secondary endpoints included SPID at additional time points, total pain relief at all on-therapy time points (TOTPAR), sum of SPID and TOTPAR at all on-therapy time points (SPID + TOTPAR), use of rescue medication, subjective pain assessment (PGIC, Patient Global Impression of Change), and adverse events (AEs). RESULTS: Analysis of the primary efficacy endpoint (SPID48) could not establish the non-inferiority of TA-ER to TA-IR. However, a post hoc analysis with a re-defined non-inferiority margin did demonstrate the non-inferiority of TA-ER to TA-IR. No statistically significant difference in SPID at 6, 12, or 24 hours was observed between the TA-ER and TA-IR groups. Similarly, analysis of TOTPAR showed that there were no significant differences between groups at any on-therapy time point, and SPID + TOTPAR at 6 and 48 hours were similar among groups. There was no difference in the mean frequency or dosage of rescue medication required by both groups, and the majority of patients in both the TA-ER and TA-IR groups rated their pain improvement as 'much' or 'somewhat better'. The overall incidence of ≥1 AEs was similar among the TA-ER (88.8%) and TA-IR (89.5%) groups. The most commonly reported AEs by patients treated with TA-ER and TA-IR included nausea (49.7% vs 44.4%), vomiting (28.0% vs 24.2%), and decreased hemoglobin (23.6% vs 26.1%). This study is limited by the lack of placebo control, and the invalidity of the initial non-inferiority margin. CONCLUSION: This study demonstrated that the analgesic effect of TA-ER is non-inferior to TA-IR, and supports TA-ER as an effective and safe treatment for moderate to severe acute pain post total knee replacement. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT01814878.

A tenosynovial giant cell tumor arising from femoral attachment of the anterior cruciate ligament.

The localized type of tenosynovial giant cell tumor usually occurs on the palmar side of fingers and toes. Tenosynovial giant cell tumors of the tendon sheath are rarely intra-articular. We report a giant cell tumor of the tendon sheath arising from femoral attachment of the anterior cruciate ligament and its treatment with arthroscopy in a 28-year-old man.

New morphological features for grading pancreatic ductal adenocarcinomas.

Pathological diagnosis is influenced by subjective factors such as the individual experience and knowledge of doctors. Therefore, it may be interpreted in different ways for the same symptoms. The appearance of digital pathology has created good foundation for objective diagnoses based on quantitative feature analysis. Recently, numerous studies are being done to develop automated diagnosis based on the digital pathology. But there are as of yet no general automated methods for pathological diagnosis due to its specific nature. Therefore, specific methods according to a type of disease and a lesion could be designed. This study proposes quantitative features that are designed to diagnose pancreatic ductal adenocarcinomas. In the diagnosis of pancreatic ductal adenocarcinomas, the region of interest is a duct that consists of lumen and epithelium. Therefore, we first segment the lumen and epithelial nuclei from a tissue image. Then, we extract the specific features to diagnose the pancreatic ductal adenocarcinoma from the segmented objects. The experiment evaluated the classification performance of the SVM learned by the proposed features. The results showed an accuracy of 94.38% in the experiment distinguishing between pancreatic ductal adenocarcinomas and normal tissue and a classification accuracy of 77.03% distinguishing between the stages of pancreatic ductal adenocarcinomas.

Automatic differential diagnosis of pancreatic serous and mucinous cystadenomas based on morphological features.

Generally, pathological diagnosis using an electron microscope is time-consuming and likely to result in a subjective judgment, because pathologists perform manual screening of tissue slides at high magnifications. Recently, the advent of digital pathology technology has provided the basis for convenient screening and quantitative analysis by digitizing tissue slides through a computer system. However, a screening process with high magnification still takes quite a long time. To solve these problems, recently the use of computer-aided design techniques for performing pathologic diagnosis has been increasing in digital pathology. For pathological diagnosis, we need different diagnostic methods for different regions with different characteristics. Therefore, in order to effectively diagnose different lesions and types of diseases, a quantitative method for extracting specific features is required in computerized pathologic diagnosis. This study is about an automated differential diagnosis system to differentiate between benign serous cystadenoma and possibly-malignant mucinous cystadenoma. In order to diagnose cystic tumors, the first step is identifying a cystic region and inspecting its epithelial cells. First, we identify the lumen boundary of a cyst using the Direction Cumulative Map considering 8-ways. Then, the Epithelial Nuclei Identification algorithm is used to discern epithelial nuclei. After that, three morphological features for the differential diagnosis of mucinous and serous cystadenomas are extracted. To demonstrate the superiority of the proposed features, the experiments compared performance of the classifiers learned by using the proposed morphological features and the classical morphological features based on nuclei. The classifiers in the simulations are as follows; Bayesian Classifier, k-Nearest Neighbors, Support Vector Machine, and Artificial Neural Network. The results show that all classifiers using the proposed features have the best classification performance.

A distal fluted, proximal modular femoral prosthesis in revision hip arthroplasty.

Most reports on the use of modular femoral stems during revision surgery have involved short follow-up periods. The authors evaluated the clinical and radiographic performance of 59 patients fitted with a distal fix modular stem. The average follow-up period was 8.2 years. Average Harris hip score was improved from 47 to 87.6. Of 19 patients with trochanteric osteotomy, 4 had a displaced greater trochanter. Re-revision was performed in 5 patients, and 3 of these were for subsidence (of these 3, subsidence was associated with dissociation of the coupling part in 1 and with osteotomy nonunion in other 2 [proximal component only]). Modular distally fixed femoral stems were found to offer intraoperative flexibility, but to suffer from subsidence and intraoperative greater trochanter and metaphyseal femoral fractures.