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BACKGROUNDEgg development has unique features that render it vulnerable to environmental perturbation. The herbicide atrazine is an endocrine disruptor shown to have detrimental effects on reproduction across a number of vertebrate species.OBJECTIVESTo determine whether exposure to low levels of atrazine impairs meiosis in female mammals using a mouse model; in particular, whether and how the fidelity of oocyte chromosome segregation is affected, and whether the aging-related aneuploidy is exacerbated.METHODSFemale C57BL/6J mice were exposed to two levels of atrazine in drinking water, with the lower level corresponding to detected environmental contamination. To model exposure during development, atrazine was ingested by pregnant females at 0.5 days post coitum and continued until pups were weaned at 21 days post-partum. For adult exposure, 2-month-old females ingested atrazine for 3 months. For each exposure group, various indicators of oocyte quality were determined, including developmental capacity and chromosomal abnormalities during the two meiotic divisions.RESULTSDevelopmental exposure caused only minor effects on the fetal events of meiotic prophase-I and establishment of initial follicle pools. However, ovulation was enhanced while oocyte quality was significantly reduced. At the chromosome level, misalignment and numerical and structural abnormalities were increased at both meiotic divisions. Furthermore, fertilization efficiency was impaired in vitro, and apoptosis was elevated in blastocysts derived from the eggs of atrazine-exposed females. Similar levels of chromosomal defects were seen in oocytes following both developmental and adult exposure regimens suggesting that quiescent primordial follicles may be the consequential targets of atrazine. Importantly, defects were observed long after exposure was terminated. Moreover, dramatic increases in chromosomally abnormal oocytes were seen in older mice indicating that atrazine exposure during development exacerbates the effects of maternal aging on oocyte quality. Indeed, analogous to the effects of maternal age, atrazine exposure resulted in weakened cohesion between sister chromatids.CONCLUSIONLow-level atrazine exposure causes persistent changes to the female mammalian germline with potential consequences for reproductive lifespan and congenital disease.

As there are limited data on the disease course of and factors predicting severe coronavirus disease 19 (COVID-19) in patients with asthma, this study aims to perform a detailed analysis of the clinical course of asthmatic patients with COVID-19 and evaluate factors related to severe infection. Of the 5,628 patients confirmed with COVID-19, 128 (2.3%) had asthma. Among the 128 asthmatic patients, 32 (25%) had severe COVID-19 and 96 (75%) had non-severe COVID-19. Among asthmatic patients, those with severe COVID-19 were significantly older and had more dyspnea and fever, more comorbidities, and lower lymphocyte and platelet counts than those with non-severe COVID-19. In multivariable logistic regression analysis, chronic obstructive pulmonary disease (adjusted odds ratio [aOR], 6.49; 95% confidence interval [CI], 1.18-41.81), low lymphocyte proportion (aOR, 0.91; 95% CI, 0.86-0.97), and low platelet count (aOR, 0.99; 95% CI, 0.98-0.99) were independently associated with severe COVID-19.

Endogenous retroviruses (ERVs) are retrotransposons present in various metazoan genomes and have been implicated in metazoan evolution as well as in nematodes and humans. The long terminal repeat (LTR) retrotransposons contain several regulatory sequences including promoters and enhancers that regulate endogenous gene expression and thereby control organismal development and response to environmental change. ERVs including the LTR retrotransposons constitute 8% of the human genome and less than 0.6% of the Caenorhabditis elegans (C. elegans) genome, a nematode genetic model system. To investigate the evolutionarily conserved mechanism behind the transcriptional activity of retrotransposons, we generated a transgenic worm model driving green fluorescent protein (GFP) expression using Human endogenous retroviruses (HERV)-K LTR as a promoter. The promoter activity of HERV-K LTR was robust and fluorescence was observed in various tissues throughout the developmental process. Interestingly, persistent GFP expression was specifically detected in the adult vulva muscle. Using deletion constructs, we found that the region from positions 675 to 868 containing the TATA box was necessary for promoter activity driving gene expression in the vulva. Interestingly, we found that the promoter activity of the LTR was dependent on che-1 transcription factor, a sensory neuron driver, and lin-15b, a negative regulator of RNAi and germline gene expression. These results suggest evolutionary conservation of the LTR retrotransposon activity in transcriptional regulation as well as the possibility of che-1 function in non-neuronal tissues. [BMB Reports 2020; 53(10): 521-526]

Response to vaccines generally varies according to individual factors of the vaccinated subjects such as demographics and immune status. While there are various reports of factors associated with immunogenicity of mRNA COVID-19 vaccines, little is known about those of adenovirus vector vaccines. We conducted a prospective observational study to assess the relationships of antibody level with age, sex, body mass index (BMI), and adverse reactions (ARs) to an adenovirus vector vaccine, ChAdOx1 nCoV-19. Healthcare workers who planned to receive both the first and second injections of the ChAdOx1 nCoV-19 vaccine at Hanyang University Hospital, Seoul, Korea, were enrolled in the study. Seven days after each injection, participants were asked to complete an online adverse reaction survey. In addition, anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) antibody concentration was measured 4 weeks after the second injection. All participants (n = 447, 100%) showed serologic positivity (≥ 0.8 U/mL) 4 weeks after the second injection of ChAdOx1 nCoV-19 vaccine. Furthermore, the anti-SARS-CoV-2 S protein RBD concentration was similar among groups when stratified by age, sex, BMI, or presence and severity of AR; multivariable linear regression found no associations between antibody response to the ChAdOx1 nCoV-19 vaccine and age, BMI, sex, and vaccine-induced ARs. In conclusion, age, sex, obesity, and ARs were not associated with antibody responses after two doses of ChAdOx1 nCoV-19 vaccination.

Objective: Limited data are available regarding the rates and risk factors of severe to serious adverse reactions (ARs) to the ChAdOx1 nCoV-19 vaccine.Methods: Eligible participants were healthcare workers who received their first dose of the ChAdOx1 nCoV-19 vaccine in either of two university hospitals in Seoul, Korea. We evaluated the type and severity of ARs 7 days after the first dose of the ChAdOx1 nCoV-19 vaccine using a questionnaire survey delivered via a smartphone application link.Results: Among the 1,603 participants who completed the survey, 684 (42.7%) participants experienced any kind of grade 3 to grade 4 AR. Being young (adjusted odds ratio [OR] for age 21–30 years = 2.49, 95% confidence interval [CI] = 1.75–3.56; adjusted OR for 31–40 years = 1.78, 95% CI = 1.22–2.62; adjusted OR for 41–50 years = 1.47, 95% CI = 1.03–2.11), being female (adjusted OR = 2.16. 95% CI = 1.62–2.89), and being underweight (adjusted OR = 1.61, 95% CI = 1.02–2.55) were identified as risk factors for grade 3 to grade 4 ARs. Among comorbidities, only diabetes mellitus (adjusted OR = 2.36, 95% CI = 1.03–5.53) was identified as a risk factor. When stratified by the type of AR, being young and being female were risk factors for both local and systemic grade 3 to grade 4 ARs.Conclusions: Being young, female, or underweight and having diabetes mellitus were associated with an increased risk of developing grade 3 to grade 4 ARs after receiving the first dose of the ChAdOx1 nCoV-19 vaccine.

The objective of this study was to investigate the quality and environment properties of traditional Gochujang produced by 56 rural farms in 8 regions of Korea for evaluating the relationship between the components and environmental factors. Based on the regional means at the initiatory and after fermentation, the ranges of moisture content, salinity, pH, and acidity of Gochujang were determined to be from 46.87±7.09% to 43.80±7.17%, from 7.52±2.21% to 8.53±2.57%, from 5.01±0.30 to 4.63±0.34, and from 1.13±0.50% to 1.43±0.58%, respectively. The mean contents of reducing sugar and amino-type nitrogen were from 16.46±7.63% to 20.48±7.57% and from 140.06±78.00 mg% to 198.68±87.11 mg%, respectively. Hunter color values (L, a, and b) of Gochujang were from 26.16±9.27 to 22.49±9.02, from 21.87±6.31 to 20.14±7.58, and from 19.43±11.94 to 19.18±12.06, respectively. Total aerobic number was increased from 6.50±1.29 log CFU/g to 8.15±0.88 log CFU/g, while the fungal number was steadily decreased after fermentation. Next generation sequencing analysis to investigate the microbial communities revealed that the dominant bacteria in Gochujang belong to the phyla of Firmicutes and Cyanobacteria. Similarly, Aspergillus spp. of the phylum Ascomycota was the predominant fungi in traditional Gochujang. Finally, according to principle component analysis of the relationship between the quality and environmental properties of Gochujang, the contents of amino-type nitrogen, salinity, titratable acidity, and reducing sugar had strong correlations with exterior humidity. These results also suggest that the quality of traditional soybean sauces can be controlled by exterior environmental change.

The aim of this work was to evaluate the potential use of recycled sewage-sludge as a biosorbent for removing various metals from aqueous solution. To improve adsorption capacity and accomplish easy solid-liquid separation, the sludge was immobilized into the rod type with Ca-alginate. The removal performance was analyzed through kinetic and equilibrium studies. We conducted batch experiments examining the removal of cationic metals and anionic metals/metalloid by the rod-type biosorbent (cations: Cd(II), Cu(II), Cr(III), Fe(II), Ni(II), Pb(II), Zn(II), Mn(II), Al(III), As(III), and Fe(III); anions: As(V), Cr(VI) and Mn(VII)).The rod-type biosorbent, which was manufactured using sludge and alginate, showed higher adsorption capability for the removal of cationic metal than anionic metal. In evaluations of cation adsorption, divalent cations adsorbed more and faster than trivalent cations. The maximum uptake of Cd(II) was determined to be 67.29 mg/g, which was higher than those of other sludge adsorbents reported in the literature. In evaluations of anions, As(V), Cr(VI) and Mn(VII) were removed by different mechanisms. In this study, we simultaneously evaluated the adsorption performance of a new biosorbent for cationic and anionic metals. Our findings are expected to contribute to the commercialization of sludge-based biosorbents.

Abstract. Optimal serum vitamin D levels are reported to be associated with many health benefits; however, few studies have determined predictive factors using national level data. An assessment of predictive factors for vitamin D inadequacy was conducted using National Health and Nutrition Examination Survey (NHANES) 2001–2006 data. Using the study sample including adults aged 40 years or more, data analysis was performed using the weighted multivariate logistic regression statistical procedure. The prevalence of vitamin D inadequacy (serum vitamin D adj=6.351; 95% CI 5.338, 7.555; padj=1.499; 95% CI 1.315, 1.708; padj=2.225; 95% CI 1.903, 2.601; p

Although protein-protein interactions (PPIs) have emerged as an attractive therapeutic target space, the identification of chemicals that effectively inhibit PPIs remains challenging. Here, we identified through library screening a chemical probe (compound 1) that can inhibit the tumor-promoting interaction between the oncogenic factor exon 2–depleted splice variant of aminoacyl–transfer RNA synthetase-interacting multifunctional protein 2 (AIMP2-DX2) and heat shock protein 70 (HSP70). We found that compound 1 binds to the N-terminal subdomain of glutathione S-transferase (GST-N) of AIMP2-DX2, causing a direct steric clash with HSP70 and an intramolecular interaction between the N-terminal flexible region and the GST-N of AIMP2-DX2, which induces masking of the HSP70 binding region during molecular dynamics and mutation studies. Compound 1 thus interferes with the AIMP2-DX2 and HSP70 interaction and suppresses the growth of cancer cells that express high levels of AIMP2-DX2 in vitro and in preliminary in vivo experiment. This work provides an example showing that allosteric conformational changes induced by chemicals can be a way to control pathologic PPIs. SIGNIFICANCE STATEMENT Compound 1 is a promising protein-protein interaction inhibitor between AIMP2-DX2 and HSP70 for cancer therapy by the mechanism with allosteric modulation as well as competitive binding. It seems to induce allosteric conformational change of AIMP2-DX2 proteins and direct binding clash between AIMP2-DX2 and HSP70. The compound reduced the level of AIMP2-DX2 in ubiquitin-dependent manner via suppression of binding between AIMP2-DX2 and HSP70 and suppressed the growth of cancer cells highly expressing AIMP2-DX2 in vitro and in preliminary in vivo experiment.

Recent development of the chemical inhibitors specific to oncogenic KRAS (Kirsten Rat Sarcoma 2 Viral Oncogene Homolog) mutants revives much interest to control KRAS-driven cancers. Here, we report that AIMP2-DX2, a variant of the tumor suppressor AIMP2 (aminoacyl-tRNA synthetase-interacting multi-functional protein 2), acts as a cancer-specific regulator of KRAS stability, augmenting KRAS-driven tumorigenesis. AIMP2-DX2 specifically binds to the hypervariable region and G-domain of KRAS in the cytosol prior to farnesylation. Then, AIMP2-DX2 competitively blocks the access of Smurf2 (SMAD Ubiquitination Regulatory Factor 2) to KRAS, thus preventing ubiquitin-mediated degradation. Moreover, AIMP2-DX2 levels are positively correlated with KRAS levels in colon and lung cancer cell lines and tissues. We also identified a small molecule that specifically bound to the KRAS-binding region of AIMP2-DX2 and inhibited the interaction between these two factors. Treatment with this compound reduces the cellular levels of KRAS, leading to the suppression of KRAS-dependent cancer cell growth in vitro and in vivo. These results suggest the interface of AIMP2-DX2 and KRAS as a route to control KRAS-driven cancers.

Automated metaphor detection is a challenging task to identify metaphorical expressions of words in a sentence. To tackle this problem, we adopt pre-trained contextualized models, e.g., BERT and RoBERTa. To this end, we propose a novel metaphor detection model, namely metaphor-aware late interaction over BERT (MelBERT). Our model not only leverages contextualized word representation but also benefits from linguistic metaphor identification theories to distinguish between the contextual and literal meaning of words. Our empirical results demonstrate that MelBERT outperforms several strong baselines on four benchmark datasets, i.e., VUA-18, VUA-20, MOH-X, and TroFi., In Proceedings of 2021 Annual Conference of the North American Chapter of the Association for Computational Linguistics. 11 pages

While aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) is a tumor suppressor, its exon 2-depleted splice variant (AIMP2-DX2 or shortly DX2) is highly expressed in human lung cancer, and the ratio of DX2 to AIMP2 increases according to the progression of lung cancer. In this study, pyrimethamine inhibited the level of DX2 (IC50 = 0.73 &micro, M) in A549 cells expressing nanoluciferase-tagged DX2. In a panel of 5 lung cancer cell lines with various DX2 levels, pyrimethamine most potently suppressed the growth of H460 cells, which express high levels of DX2 (GI50 = 0.01 &micro, M). An immunoblot assay in H460 cells showed that pyrimethamine decreased the DX2 level dose-dependently but did not affect the AIMP2 level. Further experiments confirmed that pyrimethamine resulted in ubiquitination-mediated DX2 degradation. In an in vivo mouse xenograft assay using H460 cells, intraperitoneal administration of pyrimethamine significantly reduced the tumor size and weight, comparable with the effects of taxol, without affecting body weight. Analysis of tumor tissue showed a considerably high concentration of pyrimethamine with a decreased levels of DX2. These results suggest that pyrimethamine, currently used as anti-parasite drug, could be repurposed to treat lung cancer patients expressing high level of DX2.

Maternal embryonic leucine zipper kinase (MELK) has been implicated in various cellular processes and is highly upregulated in diverse cancers, then it is thought to be a promising anticancer target. 3-Anilino-1H-pyrazolo[3,4-b]pyridine scaffold was identified as a novel scaffold for MELK kinase inhibitors in high throughput screening (HTS). From exploration for structure–activity relationship (SAR) studies mainly by the modification of the 3 (C3), and 5-positions (C5), 4-(4-methylpiperazin-1-yl)-N-{5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]-1H-pyrazolo[3,4-b]pyridin-3-yl}benzamide (21a) was found to exhibit good activity (IC50 = 0.15 μM) on MELK as a lead in early state.

Objective To describe the personality traits of temperament and character in patients with tinnitus and to identify differences in these traits associated with the severity of tinnitus. Study design Case series with comparisons. Setting Tertiary referral centre. Participants From January to December 2014, one hundred and thirty-four adult patients with chronic subjective tinnitus completed psychoacoustic measurements of tinnitus and the Temperament and Character Inventory (TCI). Measurements Personality traits were assessed by the TCI. The TCI assesses seven dimensions of personality traits and four temperaments ‘novelty seeking, harm avoidance, reward dependence, persistence’, as well as three characters ‘self-directedness, cooperativeness, self-transcendence’. Main outcome measures The values of the TCI parameters in the tinnitus patients were compared with reference data from a non-institutional adult population, and associations between TCI parameter values and tinnitus severity were evaluated. Results In terms of temperament, tinnitus patients had higher scores for ‘harm avoidance’, whereas scores for ‘novelty seeking’, ‘reward dependence’ and ‘persistence’ were significantly lower than the reference. In terms of character, lower ‘cooperativeness’ and ‘self-transcendence’ were identified in the subjects with tinnitus. The ‘novelty seeking’ score was inversely related to tinnitus severity (r = −0.285, P = 0.001), while other temperament and character traits did not show significant correlations. Conclusions There may be a connection between tinnitus and personality traits, especially in the case of ‘novelty seeking’, which is relatively constant over a lifetime. The TCI questionnaire may be useful in facilitating the application of personality traits to tailored counselling for tinnitus.

The use of activated sludge process for biological treatment of domestic and industrial wastewaters generates large amounts of sewage sludge, which is regarded as problematic biowaste. Conventional waste treatment methods such as landfilling and ocean pumping have been used to dispose the unwanted sludge, but this practice is no longer recommended due to serious secondary pollution and strict environmental regulations. Hydrothermal treatment represents a promising alternative that has attracted attention in recent years. In this study, batch experiments of hydrothermal treatment of domestic sewage sludge were conducted under varying conditions (temperature of 150–300 °C, reaction time of 0.5–3.0 h, and sludge concentration of 5–30 g/L). A statistical study of the responses, including disintegration degree and concentration of dissolved compounds, was performed using a response surface methodology. Optimal conditions for hydrothermal treatment of sewage sludge were obtained through mathematical modeling.

Sadly, there have already been nearly 200 million confirmed cases of coronavirus disease 2019 (COVID-19) and more than 4 million deaths [1]. The true toll is certainly much higher. We have learned much about the wide spectrum of disease due to COVID-19 over the past 18 months, ranging from asymptomatic infection to severe pneumonia, respiratory failure and death [2]. There is growing concern about whether survivors of COVID-19 will have long-term pulmonary sequelae, including fibrotic interstitial lung disease (ILD) and/or manifest progressive pulmonary fibrosis [3]., Pre-existing ILD and pulmonary fibrosis increases the risk to manifest severe COVID-19. Residual interstitial lung changes and sequelae have been observed in COVID-19 survivors. A closer and standardised long-term follow-up of these patients is needed. https://bit.ly/3jWBPCG

Regulator of calcineurin 1 (RCAN1) binds to calcineurin through the PxIxIT motif, which is evolutionarily conserved. SP repeat phosphorylation in RCAN1 is required for its complete function. The specific interaction between RCAN1 and calcineurin is critical for calcium/calmodulin-dependent regulation of calcineurin serine/threonine phosphatase activity. In this study, we investigated two available deletion rcan-1 mutants in Caenorhabditis elegans, which proceed differently for transcription and translation. We found that rcan-1 may be required for calcineurin activity and possess calcineurin-independent function in body growth and egg-laying behavior. In the genetic background of enhanced calcineurin activity, the rcan-1 mutant expressing a truncated RCAN-1 which retains the calcineurin-binding PxIxIT motif but misses SP repeats stimulated growth, while rcan-1 lack mutant resulted in hyperactive egg-laying suppression. These data suggest rcan-1 has unknown functions independent of calcineurin, and may be a stimulatory calcineurin regulator under certain circumstances.

Protease activated receptor 1 (PAR1) has been considered as a promising antiplatelet target to prevent thrombotic cardiovascular events in patients with prior myocardial infarction or peripheral arterial diseases. Previously, we found a series of octahydroindene analogues to have high potency on PAR1 and no significant cytotoxicity but poor metabolic stability in human and rat liver microsomes. We designed and synthesized substituted analogues of octahydroindenes at C5 or C6 aiming to improvement of metabolic stability, and identified that trans-fused 5-[(tert-butoxtycarbonyl)amino]octahydroindene analogues showed improved metabolic stability with maintaining good activity on PAR1. Especially, 2-methanesulfonate 57 (IC50 = 0.006 μM; R50 = 126.3 min in human, 83.3 min in rat), sulfamate 58 (IC50 = 0.020 μM; R50 = 52.8 min in human, 106.0 min in rat), and N-(cyclopropyl)methylsufonamide 63 (IC50 = 0.010 μM; R50 = 51.4 min in human, 90.5 min in rat) exhibited excellent activity and metabolic stability both on human and rat liver microsomes, comparable to those obtained for varapaxar (IC50 = 0.0015 μM; R50 = 83.2 min in human, 32.4 min in rat). Additionally, these compounds (57, 58, and 63) represented significant efficacy (IC50 = 0.0022, 0.0062, and 0.015 μM, each) in human washed platelet aggregation (WPA) assay without cytotoxicity and CYP3A4 inhibitory activity.

An electron-transporting triazole (Tz) and hole transporting carbazole (Cz) moieties were introduced into the fluorene structure via a Suzuki coupling reaction. The resulting material, 9-(4'-(9-(4'-(4,5-diphenyl-4H-1,2,4-triazol-3-y)-[1,1'-biphenyl]-4-yl)-9H-fluoren-9-yl)-[1,1'-biphenyl]-4-yl)-9H-carbazole (Tz-FL-Cz), was synthesized and can be used as the host layer in phosphorescent OLEDs. The synthesized material exhibits wide energy gap (3.46 eV). The absorption and emission maximum of the Tz-FL-Cz was observed at 300 nm and 389 nm, respectively. Blue phosphorescent devices using Tz-FL-Cz as host material exhibited maximum current efficiency of 3.2 cd/A and power efficiency of 1.3 lm/W, respectively.

Background:Irisin, exercise-mediated myokine, is one of the most recently discovered hormones. Irisin has been shown to play multifunctional roles including anti-inflammation by suppressing secretion of NF kß, TNF-α, IL-6, and other pro-inflammatory cytokines from macrophages and adipocytes [1]. Thus, several attempts have been made to investigate irisin in chronic inflammatory rheumatic diseases. And recent evidences show that serum irisin concentration is lower in patients with osteoarthritis, rheumatoid arthritis, and behcet disease than health individuals [2-4]. Furthermore, one study showed that serum irisin level was negatively correlated with radiographic severity of knee osteoarhtiritis [2]. However, no previous study has investigated irisin in patients with ankylosing spondylitis (AS).Objectives:To assess the serum level of irisin, and evaluate the possible relationship of irisin with disease activity in patients with AS.Methods:Male patients with AS fulfilled the modified New York criteria (n=119), and healthy male controls (n=30) were enrolled. Serum irisin level was measured by ELISA (Cusabio, CSB-EQ027943HU). Disease activity was assessed by acute phase reactants, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Clinical characteristics and serum irisin level of the AS group were compared with those of the control group using Student t-test for normally distributed continuous measures and Mann-Whitney U test for non-normally distributed continuous measures. To evaluate the correlations of serum Irisin level and AS disease activity, Spearman’s correlation test was used. AS patients were grouped into the high BASDAI group (BASDAI ≥ 4, n=45) and the Low BASDAI group (BASDAI < 4, n=74). And serum irisin level was also compared between two groups.Results:AS group had lower serum irisin concentration compared with healthy control group (60.50 [23.68-131.15] vs. 124.69 [79.58-192.90], p=0.013), while age and body mass index were not significantly different between groups. There was no significant correlation between irisin level and disease activities. However, High BASDAI group showed significantly lower irisin level than low BASDAI group (44.64 [18.13-85.89] vs. 65.68 [31.81-165.31], p=0.011).Conclusion:AS patients have lower serum irisin concentrations than healthy controls. AS patients with severe symptoms tend to have lower serum level of irisin than those with less severe symptoms.References:[1]H. Askari, et al. A glance at the therapeutic potential of irisin against diseases involving inflammation, oxidative stress, and apoptosis: an introductory review. Pharmacol Res. 2018[2]Mao Y, et al. Association of Irisin and CRP Levels with the Radiographic Severity of Knee Osteoarthritis. Genet Test Mol Biomarkers. 2016[3]Rania M. Gamal, et al. Preliminary study of the association of serum irisin levels with poor sleep quality in rheumatoid arthritis patients. Sleep Med. 2020[4]A. Icli, et al. Novel myokine: irisin may be an independent predictor for subclinic atherosclerosis in Behcet’s disease. J. Investig. Med. 2016Disclosure of Interests:None declared

Background:In the treatment of ankylosing spondylitis (AS), conventional disease-modifying antirheumatic drugs (cDMARDs) are generally recommended only in patients with peripheral arthritis. However in daily clinical practice, sulfasalazine (SSZ) and methotrexate (MTX) have still been considered on the basis of their anti-inflammatory effect when non-steroidal anti-inflammatory drugs (NSAIDs) are not available and when it is difficult to start tumor necrosis factor (TNF) inhibitors. Nonetheless there is few data about the impact of the cDMARDs on the prognosis of spinal progression.Objectives:The aim of this study was to investigate the effectiveness of SSZ and MTX on the spinal radiographic progression in patients with AS.Table 1.Association of clinical covariates and DMARD intervals with the rate of mSASSS changeVariableMultivariate analysisModel 1Model 2β (95% CI)pβ (95% CI)pOn-DMARD intervals-0.081 (-0.276 to 0.115)0.418On-SSZ intervals-0.001 (-0.211 to 0.189)0.913On-MTX intervals-0.180 (-0.439 to 0.078)0.172Sex (female)-0.449 (-0.782 to -0.117)0.008-0.440 (-0.775 to -0.105)0.010Age0.012 (-0.001 to 0.026)0.0610.012 (-0.001 to 0.025)0.076Eye involvement0.572 (0.264 to 0.880)< 0.0010.577 (0.268 to 0.886)< 0.001Peripheral joint involvement-0.508 (-0.810 to -0.206)0.001-0.513 (-0.817 to -0.210)0.001HLA-B27 positivity††NSAIDs††Glucocorticoids††ESR (log)0.176 (0.087 to 0.265)< 0.0010.178 (0.088 to 0.268)< 0.001BASDAI (square root)†††Not included in the model because the value did not show potentially significant association in univariate analysis (p > 0.1).Methods:A total of 301 patients who have been treated with cDMARDs were enrolled from 1,280 patients in a single center cohort during 18 years of follow up. For each patient, time intervals of periods were created according to the prescription records. ‘On-DMARD’ intervals were time intervals of periods with SSZ or MTX treatment and ‘off-DMARD’ intervals were time intervals of periods without both SSZ and MTX treatment. The intervals were the periods excluding the treatment periods of TNF inhibitors. Radiographic progression was evaluated by the rate of Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change, an increase or decrease of mSASSS change per year. A generalized estimating equation models with adjustment for confounding covariates were used to evaluate the efficacy of cDMARDs on the radiographic progression.Results:The number of 732 on-DMARD intervals and 1,027 off-DMARD intervals were obtained. Among the on-DMARD intervals, the proportion of intervals treated with SSZ (on-SSZ intervals), MTX (on-MTX intervals) and both of them (on-SSZ/MTX intervals) were 96.2%, 19.9% and 16.1%, respectively. In the multivariable regression analysis, there was no significant decrease in the rate of mSASSS change during cDMARDs therapy (β = -0.081, p = 0.418) (Table 1). And the mean rate of mSASSS change were 0.61 during on-DMARD intervals and 0.69 during off-DMARD intervals after adjustment of other covariates.Conclusion:Treatment with cDMARDs in AS did not show significant impact in retarding spinal progression. In patients with AS, treatment with biologics rather than cDMARDs may be more effective in slowing radiographic progression.Disclosure of Interests:None declared