IL-17 induces production of IL-6 and IL-8 in rheumatoid arthritis synovial fibroblasts via NF-κB- and PI3-kinase/Akt-dependent pathways

Recent studies of the pathogenesis of rheumatoid arthritis (RA) have revealed that both synovial fibroblasts and T cells participate in the perpetuation of joint inflammation as dynamic partners in a mutual activation feedback, via secretion of cytokines and chemokines that stimulate each other. In this study, we investigated the role of IL-17, a major Th1 cytokine produced by activated T cells, in the activation of RA synovial fibroblasts. Transcripts of IL-17R (IL-17 receptor) and IL-17RB (IL-17 receptor B) were present in fibroblast-like synoviocytes (FLS) of RA patients. IL-17R responded with increased expression upon in vitro stimulation with IL-17, while the level of IL-17RB did not change. IL-17 enhanced the production of IL-6 and IL-8 in FLS, as previously shown, but did not affect the synthesis of IL-15. IL-17 appears to be a stronger inducer of IL-6 and IL-8 than IL-15, and even exerted activation comparable to that of IL-1β in RA FLS. IL-17-mediated induction of IL-6 and IL-8 was transduced via activation of phosphatidylinositol 3-kinase/Akt and NF-κB, while CD40 ligation and p38 MAPK (mitogen-activated protein kinase) are not likely to partake in the process. Together these results suggest that IL-17 is capable of more than accessory roles in the activation of RA FLS and provide grounds for targeting IL-17-associated pathways in therapeutic modulation of arthritis inflammation

Identification and Characterization of a Dual-Acting Antinematodal Agent against the Pinewood Nematode, Bursaphelenchus xylophilus

The pinewood nematode (PWN), Bursaphelenchus xylophilus, is a mycophagous and phytophagous pathogen responsible for the current widespread epidemic of the pine wilt disease, which has become a major threat to pine forests throughout the world. Despite the availability of several preventive trunk-injection agents, no therapeutic trunk-injection agent for eradication of PWN currently exists. In the characterization of basic physiological properties of B. xylophilus YB-1 isolates, we established a high-throughput screening (HTS) method that identifies potential hits within approximately 7 h. Using this HTS method, we screened 206 compounds with known activities, mostly antifungal, for antinematodal activities and identified HWY-4213 (1-n-undecyl-2-[2-fluorphenyl] methyl-3,4-dihydro-6,7-dimethoxy-isoquinolinium chloride), a highly water-soluble protoberberine derivative, as a potent nematicidal and antifungal agent. When tested on 4 year-old pinewood seedlings that were infected with YB-1 isolates, HWY-4213 exhibited a potent therapeutic nematicidal activity. Further tests of screening 39 Caenorhabditis elegans mutants deficient in channel proteins and B. xylophilus sensitivity to Ca2+ channel blockers suggested that HWY-4213 targets the calcium channel proteins. Our study marks a technical breakthrough by developing a novel HTS method that leads to the discovery HWY-4213 as a dual-acting antinematodal and antifungal compound

Determination of an Applicable FRAX Model in Korean Women

We investigated which of the three FRAX fracture risk assessment tool models is most applicable to Korean women. For 306 postmenopausal women (mean age, 77 yr) with a hip fracture, fracture probabilities were calculated using FRAX models from Japan, Turkey and China. Data on bone mineral density (BMD) at the femoral neck were available for 103 patients. Significant differences existed among the models, independent of the inclusion of BMD in the calculation of fracture probabilities. The probabilities of both major osteoporotic fractures and hip fractures were significantly higher in the Japanese model than in the Turkish or Chinese models. In all of the models, the probabilities of a major osteoporotic fracture, but not of a hip fracture, decreased significantly if calculated without BMD values. By applying the Japanese model, the ten-year probabilities for major osteoporotic and hip fractures increased significantly with age. Our results suggest that the Japanese FRAX model might be the most appropriate for Korean women

Development of IoT-Based Sensor Tag for Smart Factory

To reduce the rate of defective products and ensure the health of employees, it has become increasingly necessary to improve air quality in factories. To do so, it is important to accurately determine the air quality in the factory first. However, currently available industry-grade sensors require complex and often separate construction processes, making them difficult to use in complicated industrial sites. In order to solve such an issue, this study developed an IoT-based sensor that can collect data such as factory temperature, humidity, CO2 levels, dust, and stench. This study has also developed software to manage the IoT-based sensors, which can transmit the data via RF communication. Sensor tags were tested for basic environmental durability, including waterproof, dustproof, and vibration standards. The sensors can be connected via USB to a computer to configure its settings and access the stored data within the sensors. Unlike other existing environmental sensors, these can be easily installed anywhere as they transmit data via wireless communication. These sensors can also be installed in the factory to check the factory’s internal pollution level in real time. The application of this sensor will enable the real-time monitoring of air pollution in factories. By locating the polluted areas accurately, it will be possible to exercise distributed control over ventilation devices to prevent further spread of pollutants, while also pushing out the polluted air to maintain an optimal working environment. Future studies should develop a simulation model for determining the ideal installation location for the sensors. There also needs to be further studies in developing a distributed-controlled air-conditioning system to run empirical tests

Perioperative Risk of Hip Arthroplasty in Patients with Cirrhotic Liver Disease

We retrospectively reviewed the complete medical records of 30 patients with a diagnosis of liver cirrhosis who had undergone hip arthroplasty at three academic institutions between October 1994 and May 2001. There were 26 males and 4 females with a mean age of 60 yr at index operation. Surgical procedures included 17 primary total hip arthroplasties (THA), 8 bipolar hemiarthroplasties, and 5 revision THAs. According to the Child-Pugh scoring system, 19 cirrhotic patients were categorized as class A, 9 as class B, and 2 as class C. Eight (26.7%) of the 30 patients had one or more perioperative complications. Of these, wound infection was the most common, with a rate of 10% (3 of 30 hips). Other perioperative complications included surgical site bleeding, coagulopathy, encephalopathy, gastrointestinal bleeding, pneumonia, and arrhythmia. Death occurred in 2 (6.7%) of the 30 patients; both were Child-Pugh's C cirrhotics. A higher Child-Pugh score (p=0.0001) and a high level of creatinine (p=0.0499) were associated with significantly increased perioperative complications or death. Our findings suggest that surgeons should be vigilant about perioperative complications in patients with advanced cirrhotic liver disease who undergo hip arthroplasty, albeit the mortality rates are relatively low in less severe cirrhotics

Additive harmful effects of acute kidney injury and acute heart failure on mortality in hospitalized patients

Background Organ crosstalk between the kidney and the heart has been suggested. Acute kidney injury (AKI) and acute heart failure (AHF) are well-known independent risk factors for mortality in hospitalized patients. This study aimed to investigate if these conditions have an additive effect on mortality in hospitalized patients, as this has not been explored in previous studies. Methods We retrospectively reviewed the records of 101,804 hospitalized patients who visited two tertiary hospitals in the Republic of Korea over a period of 5 years. AKI was diagnosed using serum creatinine-based criteria, and AHF was classified using International Classification of Diseases codes within 2 weeks after admission. Patients were divided into four groups according to the two conditions. The primary outcome was all-cause mortality. Results AKI occurred in 6.8% of all patients (n = 6,920) and AHF in 1.2% (n = 1,244). Three hundred thirty-one patients (0.3%) developed both conditions while AKI alone was present in 6,589 patients (6.5%) and AHF alone in 913 patients (0.9%). Among the 5,181 patients (5.1%) who died, 20.8% died within 1 month. The hazard ratio for 1-month mortality was 29.23 in patients with both conditions, 15.00 for AKI only, and 3.39 for AHF only. The relative excess risk of interaction was 11.85 (95% confidence interval, 2.43‒21.27), and was more prominent in patients aged <75 years and those without chronic heart failure. Conclusion AKI and AHF have a detrimental additive effect on short-term mortality in hospitalized patients

Diode Laser—Can It Replace the Electrical Current Used in Endoscopic Submucosal Dissection?

Background/Aims A new medical fiber-guided diode laser system (FDLS) is expected to offer high-precision cutting with simultaneous hemostasis. Thus, this study aimed to evaluate the feasibility of using the 1,940-nm FDLS to perform endoscopic submucosal dissection (ESD) in the gastrointestinal tract of an animal model. Methods In this prospective animal pilot study, gastric and colorectal ESD using the FDLS was performed in ex vivo and in vivo porcine models. The completeness of en bloc resection, the procedure time, intraprocedural bleeding, histological injuries to the muscularis propria (MP) layer, and perforation were assessed. Results The en bloc resection and perforation rates in the ex vivo study were 100% (10/10) and 10% (1/10), respectively; those in the in vivo study were 100% (4/4) and 0% for gastric ESD and 100% (4/4) and 25% (1/4) for rectal ESD, respectively. Deep MP layer injuries tended to occur more frequently in the rectal than in the gastric ESD cases, and no intraprocedural bleeding occurred in either group. Conclusions The 1,940-nm FDLS was capable of yielding high en bloc resection rates without intraprocedural bleeding during gastric and colorectal ESD in animal models