Diagnostic Performances of Anti-Cyclic Citrullinated Peptides Antibody and Antifilaggrin Antibody in Korean Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown etiology. We studied the diagnostic performances of anti-cyclic citrullinated peptides antibody (anti-CCP) assay and recombinant anti-citrullinated filaggrin antibody (AFA) assay by enzyme linked immunosorbent assay (ELISA) in patients with RA in Korea. Diagnostic performances of the anti-CCP assay and AFA assay were compared with that of rheumatoid factor (RF) latex fixation test. RF, anti-CCP, and AFA assays were performed in 324 RA patients, 251 control patients, and 286 healthy subjects. The optimal cut off values of each assay were determined at the maximal point of area under the curve by receiver-operator characteristics (ROC) curve. Sensitivity (72.8%) and specificity (92.0%) of anti-CCP were better than those of AFA (70.3%, 70.5%), respectively. The diagnostic performance of RF showed a sensitivity of 80.6% and a specificity of 78.5%. Anti-CCP and AFA showed positivity in 23.8% and 17.3% of seronegative RA patients, respectively. In conclusion, we consider that anti-CCP could be very useful serological assay for the diagnosis of RA, because anti-CCP revealed higher diagnostic specificity than RF and AFA at the optimal cut off values and could be performed by easy, convenient ELISA method

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 <it>in vitro</it>. The mice immunized with i.n. PEI/pci-S nanoparticles produced significantly (<it>P </it>< 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-A^d) 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.</p> <p>Conclusion</p> <p>These results showed that intranasal immunization with PEI/pci-S nanoparticles induce antigen specific humoral and cellular immune responses.</p

Treatment of two Asiatic black bears (Ursus thibetanus) with severe injuries and their subsequent release into the wild: a case report

Background The rehabilitation of injured wildlife and their subsequent release into the wild is a humane act as well as important in wildlife conservation. However, little is known about the animals fate after release. Therefore, to address these uncertainties, it is essential to adequately describe how the injured animals were treated and managed before releasing into the wild; moreover, post-release monitoring should also be performed. Herein, we document for the first time the process of rescue, surgery, and rehabilitation of severely injured Asiatic black bears (Ursus thibetanus; endangered species in South Korea) and their fate after returning to the wild. Case presentation A six-year-old female (bear-01) and a three-year-old male (bear-02) bears were injured by an illegal snare and collision with a bus, respectively. Bear-01 had broad muscle necrosis and ruptures from the snared ankle on the right thoracic limb, with myiasis, and elbow disarticulation was performed. In bear-02, a non-reducible comminuted fracture of the left humerus was confirmed radiologically, and the operation was performed by using dual plate fixation with hydroxyapatite and recombinant human bone morphogenetic protein-2. The bear-01 and -02 were completely healed approximately 30 and 60 days after surgery, respectively. After that, they underwent rehabilitation for 8 and 25 days, respectively, in an outdoor enclosure similar to their natural habitat. Bear-01 and -02 were released into the wild after 45 and 99 days after surgery, respectively, and their mean daily movement distance during the first 30 days after releasing was 2.9 ± 2.1 and 1.3 ± 1.6 km, respectively. The annual mean 95% Kernel home-range size of bear-01 and bear-02 was 265.8 and 486.9 km2, respectively. They hibernated every winter, gained weight, gave birth to cubs (bear-01), were not found to have any abnormalities in the veterinary tests, and were not involved in any conflicts with humans after returning to the wild. Conclusions Bears without one leg or those with dual plates could adapt well in their natural habitat, which shows that our surgical and post-operative treatments were effective. Additionally, minimizing human contact and observing/evaluating behavior during the rehabilitation is essential in reducing human-bear conflicts after release.This work conducted as part of a restoration project of endangered Asiatic black bears by the Ministry of Environment. In addition, this work was financially supported by a grant of the Korea Health Technology Development R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI19C0642), Rural Development Administration, Republic of Korea and Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET) through Useful Agricultural Life Resources Industry Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFR A)(120054021HD020). These three funders had no role in the study design, data collection and analysis, interpretation of the results, manuscript preparation, or decision to disseminate and publish the study findings

Reduction of cycles of neoadjuvant chemotherapy for advanced epithelial ovarian, fallopian or primary peritoneal cancer (ROCOCO): study protocol for a phase III randomized controlled trial

Primary debulking surgery (PDS) and adjuvant chemotherapy is the standard treatment for advanced ovarian, fallopian or primary peritoneal cancer. However, neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) has been introduced as an alternative, showing similar efficacy and decreased postoperative complications compared with PDS. Although there is still no evidence for whether three or four cycles of NAC used clinically could be adequate, reducing one cycle of NAC is expected to remove more visible tumours and thereby improve prognosis. Thus, we proposed with this study to evaluate the efficacy and safety of reducing one cycle of NAC for advanced ovarian, fallopian or primary peritoneal cancer. This study is a prospective, multi-centre, open-label, randomized phase III trial. A total of 298 patients with advanced ovarian, fallopian or primary peritoneal cancer will be recruited and randomly assigned to either three (control group) or two cycles of NAC (experimental group). After the NAC, we will conduct IDS with maximal cytoreduction and then administer the remaining three or four cycles for a total of six cycles of adjuvant chemotherapy. The primary end point is progression-free survival, and the secondary end points are time to tumour progression, overall survival, tumour response after NAC, IDS and adjuvant chemotherapy, radiologic investigation after IDS, tumour response by positron emission tomography-computed tomography after NAC, quality of life, adverse events, success rate of optimal cytoreduction, surgical complexity, postoperative complications and safety of IDS. We will assess these factors at screening, at every cycle of chemotherapy, at IDS, after the completion of chemotherapy, every 3 months for the first 2 years after the planned treatment and every 6 months thereafter for 3 years. We hypothesize that reducing one cycle of NAC will contribute to more resection of visible tumours despite 10% reduction of optimal cytoreduction, which could improve survival. Moreover, two cycles of NAC may increase postoperative complications by 5% compared with three cycles, which may be acceptable. This study has been prospectively registered at ClinicalTrials.gov on Oct. 2nd, 2018 (NCT03693248, URL: https://clinicaltrials.gov/ct2/show/NCT03693248).Shin Poong. Pharm. Co., Ltd. plays no role in the study design, data collection, data analysis, data interpretation, or writing for the current study

Interrelationship of Pyrogenic Polycyclic Aromatic Hydrocarbon (PAH) Contamination in Different Environmental Media

Interrelationships between pyrogenic polycyclic aromatic hydrocarbons (PAHs) were assessed in air, soil, water, sediment, and tree leaves by using multi-media monitoring data. Concurrent concentration measurements were taken bimonthly for a year for the multi-media at urban and suburban sites. PAH level correlations between air and other media were observed at the urban site but were less clear at the suburban site. Considering a closer PAHs distribution/fate characteristics to soil than suspended solids, contamination in sediment seemed to be governed primarily by that in soil. The partitioning of PAHs in waters could be better accounted for by sorption onto black carbon and dissolved organic carbon

Safety and efficacy study of laparoscopic or robotic radical surgery using an endoscopic stapler for inhibiting tumour spillage of cervical malignant neoplasms evaluating survival (SOLUTION): a multi-centre, open-label, single-arm, phase II trial protocol

The Laparoscopic Approach to Cervical Cancer trial and Surveillance, Epidemiology, and End Results program database study demonstrated that minimally invasive radical hysterectomy was inferior to abdominal radical hysterectomy in terms of disease recurrence and survival. Among risk factors related to poor prognosis after minimally invasive surgery (MIS), tumour spillage during intracorporeal colpotomy became a significant issue. Thus, we designed this trial to evaluate the efficacy and safety of minimally invasive radical hysterectomy using an endoscopic stapler for early-stage cervical cancer. This trial is a prospective, multi-centre, open-label, single-arm, non-inferiority phase II study. The nine organisations will participate in this trial after the approval of the institutional review board. Major eligibility criteria include women aged 20 years or older with cervical cancer stage IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma according to the revised 2009 FIGO staging system who will undergo type B2 or C hysterectomy by MIS. The primary endpoint is the 4.5-year disease-free survival (DFS) rate between abdominal radical hysterectomy and MIS using an endoscopic stapler. For calculating the sample size, we hypothesised that the 4.5-year DFS rate after MIS using an endoscopic stapler is assumed to be the same after abdominal radical hysterectomy at 90.9%, and the non-inferiority margin was 7.2%. When we consider a three-year accrual and 4.5-year follow-up, at least 13 events must happen, requiring a total of 111 patients assuming a statistical power of 80% and the one-tailed test of 5% significance. A total of 124 patients is needed, considering a drop-out rate of 10%. We expect intracorporeal colpotomy using an endoscopic stapler may prevent tumour spillage during MIS for stage IB1 cervical cancer, showing a comparable prognosis with abdominal radical surgery.This study was supported by Johnson & Johnson. The funder has no role in study design, writing of the manuscript and the decision to submit the report for publication

Universal field-tunable terahertz emission by ultrafast photoinduced demagnetization in Fe, Ni, and Co ferromagnetic films

We report a universal terahertz (THz) emission behavior from simple Ni, Fe, and Co metallic ferromagnetic films, triggered by the femtosecond laser pulse and subsequent photoinduced demagnetization on an ultrafast time scale. THz emission behavior in ferromagnetic films is found to be consistent with initial magnetization states controlled by external fields, where the hysteresis of the maximal THz emission signal is observed to be well-matched with the magnetic hysteresis curve. It is experimentally demonstrated that the ultrafast THz emission by the photoinduced demagnetization is controllable in a simple way by external fields as well as pump fluences. © 2020, The Author(s).1

Role of non-thermal electrons in ultrafast spin dynamics of ferromagnetic multilayer

Understanding of ultrafast spin dynamics is crucial for future spintronic applications. In particular, the role of non-thermal electrons needs further investigation in order to gain a fundamental understanding of photoinduced demagnetization and remagnetization on a femtosecond time scale. We experimentally demonstrate that non-thermal electrons existing in the very early phase of the photoinduced demagnetization process play a key role in governing the overall ultrafast spin dynamics behavior. We simultaneously measured the time-resolved reflectivity (TR-R) and the magneto-optical Kerr effect (TR-MOKE) for a Co/Pt multilayer film. By using an extended three-temperature model (E3TM), the quantitative analysis, including non-thermal electron energy transfer into the subsystem (thermal electron, lattice, and spin), reveals that energy flow from non-thermal electrons plays a decisive role in determining the type I and II photoinduced spin dynamics behavior. Our finding proposes a new mechanism for understanding ultrafast remagnetization dynamics. © 2020, The Author(s).1

Study design and rationale of "Synergistic Effect of Combination Therapy with Cilostazol and ProbUcol on Plaque Stabilization and Lesion REgression (SECURE)" study: a double-blind randomised controlled multicenter clinical trial

<p>Abstract</p> <p>Background</p> <p>Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux.</p> <p>Methods/design</p> <p>The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE) study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study.</p> <p>Discussion</p> <p>The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol.</p> <p>Trial registration number</p> <p>ClinicalTrials (NCT): <a href="http://www.clinicaltrials.gov/ct2/show/NCT01031667">NCT01031667</a></p