Quantification of The Performance of CMIP6 Models for Dynamic Downscaling in The North Pacific and Northwest Pacific Oceans

Selecting a reliable global climate model as the driving forcing in simulations with dynamic downscaling is critical for obtaining a reliable regional ocean climate. With respect to their accuracy in providing physical quantities and long-term trends, we quantify the performances of 17 models from the Coupled Model Inter-comparison Project Phase 6 (CMIP6) over the North Pacific (NP) and Northwest Pacific (NWP) oceans for 1979–2014. Based on normalized evaluation measures, each model’s performance for a physical quantity is mainly quantified by the performance score (PS), which ranges from 0 to 100. Overall, the CMIP6 models reasonably reproduce the physical quantities of the driving variables and the warming ocean heat content and temperature trends. However, their performances significantly depend on the variables and region analyzed. The EC-Earth-Veg and CNRM-CM6-1 models show the best performances for the NP and NWP oceans, respectively, with the highest PS values of 85.89 and 76.97, respectively. The EC-Earth3 model series are less sensitive to the driving variables in the NP ocean, as reflected in their PS. The model performance is significantly dependent on the driving variables in the NWP ocean. Nevertheless, providing a better physical quantity does not correlate with a better performance for trend. However, MRI-ESM2-0 model shows a high performance for the physical quantity in the NWP ocean with warming trends similar to references, and it could thus be used as an appropriate driving forcing in dynamic downscaling of this ocean. This study provides objective information for studies involving dynamic downscaling of the NP and NWP oceans

GAIT ANALYSIS OF THE NORMAL AND ACL DEFICIENT PATIENTS AFTER LIGAMENT RECONSTRUCTION SURGERY

Anterior cruciate ligament (ACL) injury of the knee is common in sports. A serious ACL injury leads to ligament reconstruction surgery. In order to evaluate result of surgery or optimize the rehabilitation process, a knee condition must be objectively identified. The purpose of this study is, therefore, to numerically indicate and classify knee condition of patients via the chaos analysis. Lyapunov exponents (LyEs) were used for the comparison of the normal and the patients

Mycobacterium abscessus activates the NLRP3 inflammasome via Dectin-1–Syk and p62/SQSTM1

Numerous atypical mycobacteria, including Mycobacterium abscessus (Mabc), cause nontuberculous mycobacterial infections, which present a serious public health threat. Inflammasome activation is involved in host defense and the pathogenesis of autoimmune diseases. However, inflammasome activation has not been widely characterized in human macrophages infected with atypical mycobacteria. Here, we demonstrate that Mabc robustly activates the nucleotide binding and oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome via dectin-1/Syk-dependent signaling and the cytoplasmic scaffold protein p62/SQSTM1 (p62) in human macrophages. Both dectin-1 and Toll-like receptor 2 (TLR2) were required for Mabc-induced mRNA expression of pro-interleukin (IL)-1β, cathelicidin human cationic antimicrobial protein-18/LL-37 and β-defensin 4 (DEFB4). Dectin-1-dependent Syk signaling, but not that of MyD88, led to the activation of caspase-1 and secretion of IL-1β through the activation of an NLRP3/apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) inflammasome. Additionally, potassium efflux was required for Mabc-induced NLRP3/ASC inflammasome activation. Furthermore, Mabc-induced p62 expression was critically involved in NLRP3 inflammasome activation in human macrophages. Finally, NLRP3/ASC was critical for the inflammasome in antimicrobial responses to Mabc infection. Taken together, these data demonstrate the induction mechanism of the NLRP3/ASC inflammasome and its role in innate immunity to Mabc infection

Risk Factors of Drug Interaction between Warfarin and Nonsteroidal Anti-Inflammatory Drugs in Practical Setting

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to interact with the oral anticoagulant warfarin and can cause a serious bleeding complication. In this study, we evaluated the risk factors for international normalized ratio (INR) increase, which is a surrogate marker of bleeding, after addition of an NSAID in a total of 98 patients who used warfarin. Patient age, sex, body mass index, maintenance warfarin dose, baseline INR, coadministered medications, underlying diseases, and liver and kidney functions were evaluated for possible risk factors with INR increase ≥15.0% as the primary end-point. Of the 98 patients, 39 (39.8%) showed an INR elevation of ≥15.0% after adding a NSAID to warfarin therapy. Multivariate analysis showed that high maintenance dose (>40 mg/week) of warfarin (P=0.001), the presence of coadministered medications (P=0.024), the use of meloxicam (P=0.025) and low baseline INR value (P=0.03) were the risk factors for INR increase in respect to NSAID-warfarin interaction. In conclusion, special caution is required when an NSAID is administered to warfarin users if patients are taking warfarin >40 mg/week and other medications interacting with warfarin

Relationship between Vitamin D, Parathyroid Hormone, and Bone Mineral Density in Elderly Koreans

There is controversy regarding definition of vitamin D inadequacy. We analyzed threshold 25-hydroxyvitamin D (25[OH]D) below which intact parathyroid hormone (iPTH) increases, and examined age- and sex-specific changes of 25(OH)D and iPTH, and association of 25(OH)D and iPTH with bone mineral density (BMD) in elderly Koreans. Anthropometric parameters, serum 25(OH)D and iPTH, lumbar spine and femur BMD by dual-energy radiography absorptiometry (DXA) were measured in 441 men and 598 postmenopausal women. iPTH increased below serum 25(OH) of 36.7 ng/mL in men, but failed to reach plateau in women. Femur neck BMD above and below threshold differed when threshold 25(OH)D concentrations were set at 15-27.5 ng/mL in men, and 12.5-20 ng/mL in postmenopausal women. Vitamin D-inadequate individuals older than 75 yr had higher iPTH than those aged ≤ 65 yr. In winter, age-associated iPTH increase in women was steeper than in summer. In conclusion, vitamin D inadequacy threshold cannot be estimated based on iPTH alone, and but other factors concerning bone health should also be considered. Older people seemingly need higher 25(OH)D levels to offset age-associated hyperparathyroidism. Elderly vitamin D-inadequate women in the winter are most vulnerable to age-associated hyperparathyroidism

The Effect of Simvastatin on the Proliferation and Differentiation of Human Bone Marrow Stromal Cells

Statins have been postulated to affect the bone metabolism. Recent experimental and epidemiologic studies have suggested that statins may also have bone protective effects. This study assessed the effects of simvastatin on the proliferation and differentiation of human bone marrow stromal cells (BMSCs) in an ex vivo culture. The bone marrow was obtained from healthy donors. Mononuclear cells were isolated and cultured to osteoblastic lineage. In the primary culture, 10-6 M simvastatin diminished the mean size of the colony forming units-fibroblastic (CFU-Fs) and enhanced matrix calcification. At near confluence, the cells were sub-cultured. Thereafter, the alkaline phosphatase (ALP) activities of each group were measured by the time course of the secondary culture. Simvastatin increased the ALP activity in a dose dependent manner, and this stimulatory effect was more evident during the early period of culture. A 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay was performed during the secondary culture in order to estimate the effect of simvastatin on the proliferation of human BMSCs. When compared to the control group, simvastatin significantly decreased the proliferation of cells of each culture well. 10-6 M of simvastatin also significantly enhanced the osteocalcin mRNA expression level. This study shows that simvastatin has a stimulatory effect on bone formation through osteoblastic differentiation, and has an inhibitory effect on the proliferative potential of human BMSC

KCHO-1, a Novel Antineuroinflammatory Agent, Inhibits Lipopolysaccharide-Induced Neuroinflammatory Responses through Nrf2-Mediated Heme Oxygenase-1 Expression in Mouse BV2 Microglia Cells

The brain is vulnerable to oxidative stress and inflammation that can occur as a result of aging or neurodegenerative diseases. Our work has sought to identify natural products that regulate heme oxygenase (HO)-1 and to determine their mechanism of action in neurodegenerative diseases. KCHO-1 is a novel herbal therapeutic containing 30% ethanol (EtOH) extracts from nine plants. In this study, we investigated the antineuroinflammatory effects of KCHO-1 in lipopolysaccharide- (LPS-) treated mouse BV2 microglia. KCHO-1 inhibited the protein expression of inducible nitric oxide synthase (iNOS), iNOS-derived nitric oxide (NO), cyclooxygenase- (COX-) 2, and COX-2-derived prostaglandin E2 (PGE2) in LPS-stimulated BV2 microglia. It also reduced tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 production. This effect was correlated with the suppression of inhibitor of nuclear factor kappa B-α (IκB-α) phosphorylation and degradation and nuclear factor kappa B (NF-κB) translocation and DNA binding. Additionally, KCHO-1 upregulated HO-1 expression by promoting nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in mouse BV2 microglia. Tin protoporphyrin (SnPP), an HO activity inhibitor, was used to verify the inhibitory effects of KCHO-1 on proinflammatory mediators and proteins associated with HO-1 expression. Our data suggest that KCHO-1 has therapeutic potential in neurodegenerative diseases caused by neuroinflammation

The Effects of Antidepressant Treatment on Serum Cytokines and Nutritional Status in Hemodialysis Patients

The aim of this study was to investigate the effects of antidepressant treatment on serum cytokines and nutritional status in hemodialysis patients. Twenty-eight hemodialysis patients with a depressed mood were given 20 mg of fluoxetine for 8 weeks. The degree of depressive symptoms, the serum levels of interleukin-1β, interleukin-2, interleukin-6, tumor necrosis factor-α, c-reactive protein, and markers of nutritional status were assessed at baseline and after treatment. The outcome was assessed in terms of response to treatment (>50% reduction in the score of the Hamilton depression rating scale). Antidepressant treatment decreased the serum level of interleukin-1β in both response and nonresponse groups, and increased the serum level of interleukin-6 only in the response group. At baseline, the level of interleukin-6 in the response group was lower than in the nonresponse group. Antidepressant treatment also increased fat distribution significantly in the response group which might have slightly improved the nutritional status. This study suggests that antidepressant treatment improve depressive symptoms and may affect immunological functions and nutritional status in chronic hemodialysis patients with depression

Composite polymer electrolyte membrane decorated with porous titanium oxide nanotubes for fuel cell operating under low relative humidity

A block copolymer composite membrane of sulfonated poly(arylene ether sulfone ketone) (SPESK) decorated with porous hygroscopic titanium oxide nanotubes (TNT) is designed and fabricated for low relative humidity (RH) operating polymer electrolyte fuel cells (PEFCs). The SPESK-TNT composite membrane in a PEFC operated at 100% RH, and 80 °C resulted in about 1.3 and 1.1-folds higher power density in comparison with the benchmark Nafion (NRE-212) and pristine SPESK membranes at 0.6 V. Further, operating under 30% RH and 80 °C, the SPESK-TNT composite membrane generates 3.8 and 2.8-folds improved power density in comparison with the pristine SPESK and commercial NRE-212 membranes, respectively, at 0.6 V. An outstanding improvement of PEFC performance using SPESK-TNT composite membrane also maintains relative to a SPESK-TiO2 nanoparticles composite membrane, operating under 100 and 30% RH. Moreover, the SPESK-TNT composite membrane shows a stable operating potential of more than 200 h at 30% RH and 80 °C, confirming the durable PEFC operation. The enhanced PEFC performance under dry conditions is mainly the result of improving water management by the TNT filler in the membrane and cathode catalyst utilization, yielding significantly suppressing both ohmic and mass transport overpotentials. © 20211