AA Amyloidosis: A Contemporary View.

PURPOSE OF REVIEW: Amyloid A (AA) amyloidosis is an organ- or life-threatening complication of chronic inflammatory disorders. Here, we review the epidemiology, causes, pathogenesis, clinical features, and diagnostic and therapeutic strategies of AA amyloidosis. RECENT FINDINGS: The incidence of AA amyloidosis has declined due to better treatment of the underlying diseases. Histopathological examination is the gold standard of diagnosis, but magnetic resonance imaging can be used to detect cardiac involvement. There is yet no treatment option for the clearance of amyloid fibril deposits; therefore, the management strategy primarily aims to reduce serum amyloid A protein. Anti-inflammatory biologic agents have drastically expanded our therapeutic armamentarium. Kidney transplantation is preferred in patients with kidney failure, and the recurrence of amyloidosis in the allograft has become rare as transplant recipients have started to benefit from the new agents. The management of AA amyloidosis has been considerably changed over the recent years due to the novel therapeutic options aiming to control inflammatory activity. New agents capable of clearing amyloid deposits from the tissues are still needed.

Utility of positron emission tomography as a new tool for muscle involvement in patients with idiopathic inflammatory myositis: a controlled study.

OBJECTIVES: Idiopathic inflammatory myositis (IIM) represents a rare group of disease that can affect multiple organs in addition to the muscles. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is an emerging scanning method that is widely used in diagnosing, staging and response to treatment in patients with cancer. In this study, we aimed to evaluate the muscle involvement in PET/CT which was performed for malignancy screening and its correlation with myositis-specific antibodies (MSA) and/or myositis-associated antibodies (MAA) in patients with IIM. METHODS: IIM patients who fulfilled 2017 EULAR/ACR classification criteria and had PET-CT scans during the active phase of myositis (within two weeks of starting steroids) were included into the study. Age and sex matched participants with history of malignancy (non-IIM patients) were defined as control group. RESULTS: Data of 160 IIM patients were evaluated and 34 patients (of 64.7% female) whose PET/CT results were available, included into the study. Fourteen patients with diagnosis of malignancy without IIM (non-IIM patients) defined as the control group. Sensitivity and specificity of a positive FDG muscle uptake were 37.1% and 100%, 65.7% and 92.9%, 91.4% and 7.1% compared to liver, mediastinum and LTM uptakes, respectively. In multivariate analysis, higher baseline CRP (p=0.017, confidence interval [CI] 95%: 1.03-1.36, OR:1.18) and LDH (p=0.029, CI 95%:1.001-1.017, OR:1.01) levels were associated with muscle PET/CT positivity. CONCLUSIONS: In patients with active IIM, median muscle FDG uptake with PET/CT was higher compared to non-IIM. PET/CT may be used for the evaluation of extent and activity in patients with IIM.

Analysis of 5-year hospitalization data of patients with systemic lupus erythematosus: Damage is a risk factor for frequent and longer stays.

OBJECTIVE: The annual hospitalization rate of patients with systemic lupus erythematosus (SLE) is approximately 10%, and hospitalizations are responsible for most of the healthcare expenses. Herein, we analyzed 5-year hospitalization data of SLE patients and determined factors leading to hospitalization. METHODS: Clinical, laboratory, and hospitalization data of SLE patients admitted to our rheumatology clinic in 2015-2020 were retrieved from our SLE database and analyzed. SLICC SLE damage index (SDI) and disease activity at admission (SLEDAI-2K) were determined. RESULTS: Among 161 hospitalized patients, 86% were females. Total rheumatologic hospitalization number was 298, and 38% of the patients were hospitalized more than once (1.85 ± 1.56). The mean hospitalization duration covering all stays for each patient was 25 ± 26.5 days. Active disease, infection, and damage-related complications were first three causes of hospitalization. Compared to patients hospitalized for active disease or damage, patients hospitalized for infection had a significantly higher number of readmissions (p < .05) and their total hospital stay was longer (p < .01).The frequency of patients with damage and the mean SDI score was significantly lower in the active disease group (68%, 1.93 ± 2.05) than hospitalizations for infection (90%, 2.68 ± 1.63) and damage-related causes (96%, 3.04 ± 1.65) (p < .05). The mean SDI score and duration (r = 0.551, p < .001) and the number of hospitalizations (r = 0.393, p < .001) were positively correlated. The mean disease activity scores of patients hospitalized for active disease, infection, and damage-related reasons were 11.03 ± 6.08, 3.21 ± 2.80, and 2.96 ± 3.32, respectively (p < .001). Renal active disease was the most common (44%), followed by hematological (34.8%), articular (21.7%), and mucocutaneous (21%) activity.Ten percent of the patients all of whom had damage were admitted to intensive care unit (ICU). Total hospitalization duration, mean SDI, antiphospholipid syndrome, lupus anticoagulant, thrombocytopenia, serositis, pulmonary hypertension, history of alveolar hemorrhage, and cardiac valve involvement were associated with ICU admission (p < .05 for all). CONCLUSION: Disease activity, infections, and damage are the leading causes of hospitalization in SLE patients. Damage prolongs hospital stay and increases hospitalization rate and ICU need. Tight control of disease activity with rational use of immunosuppressive treatment is important to reduce damage and hospitalizations.

Intracranial granuloma in a patient with granulomatosis with polyangiitis under rituximab maintenance: A case report.

BACKGROUND: Rituximab (RTX) is being used for both induction and maintenance of anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis. However, the efficacy of RTX for the granulomatous findings of granulomatosis with polyangiitis (GPA) has not been demonstrated as clearly as its vasculitic manifestations. CASE SUMMARY: A 46-year-old man was diagnosed in 2019 with GPA with constitutional symptoms, bilateral mastoiditis, prostatic necrosis, nodules in both lungs, pauci-immune necrotizing glomerulonephritis and high level of PR3-ANCA. He reached clinical remission after induction with high-dose corticosteroids and intravenous cyclophosphamide pulses at the 3rd month. Two months following the second cycle of RTX as maintenance, he developed multiple cranial mass lesions, and excisional biopsy revealed necrotizing vasculitis with granuloma formation. Remission was achieved with long-term high-dose corticosteroid therapy after surgical excision. CONCLUSION: We observed a relapse of GPA with intracranial granulomatous lesions in a patient under RTX maintenance. Limited efficacy of RTX should be considered for mainly granulomatous manifestations in patients with GPA.

Characteristics and course of patients with AA amyloidosis: single centre experience with 174 patients from Turkey.

OBJECTIVES: This study aimed to evaluate the clinical, laboratory and genetic characteristics and outcomes of patients with AA amyloidosis. METHODS: Patients followed up in a tertiary referral centre in Turkey with the diagnosis of inflammatory rheumatic diseases and immunohistologically proven AA amyloidosis were included in the study and retrospectively analysed. RESULTS: Among 184 patients with the diagnosis of AA amyloidosis, 174 (83 female, 91 male) were included in the analysis. The most common cause of AA amyloidosis was FMF (78.7%), and 91% of FMF-AA amyloidosis patients were carrying the p.M694V variant (74.1% homozygous). AA amyloidosis was identified earlier in patients with homozygous or compound heterozygous MEFV exon 10 variants compared with the heterozygous patients (27, 30 and 41 years, respectively). Patients with an estimated glomerular filtration rate <60 ml/min at admission had a higher frequency of progression to end-stage renal disease (P < 0.001). The overall mortality rate was 15.3% and it increased gradually in association with the amyloid burden (10% in patients with renal, 15% in renal + gastrointestinal and 43% in those with additional cardiac involvement). Renal findings responded completely to treatment in 31% of the patients, a partial response was observed in 4%, a stable course in 23.6% and progression in 38.5%. Amyloid storm was identified in nine patients and was found to be associated with increased mortality within 1 year. CONCLUSION: FMF patients still constitute the majority of AA amyloidosis patients in Turkey. The MEFV genotype and associated inflammatory load may affect the age of onset of AA amyloidosis, and earlier diagnosis and stricter follow-up and treatment may delay progression of the disease.

Validation of the PEDiatric Behçet's Disease classification criteria: an evidence-based approach.

OBJECTIVES: to validate the PEDiatric Behçet's Disease classification criteria (PEDBD) with an evidence-based approach. METHODS: 210 pediatric patients (70 Behçet's disease (BD), 40 Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitis, 35 familial Mediterranean fever, 26 hyper-IgD syndrome, 22 TNF-Receptor associated Periodic fever Syndrome, 17 undefined recurrent fevers) were randomly selected from the Eurofever Registry. A set of 11 experienced clinicians/researchers blinded to the original diagnosis evaluated the patients. Using the table consensus as gold standard (agreement ≥ 80%), the PEDBD, ISG and ICBD criteria were applied to BD patients and to confounding diseases with other autoinflammatory conditions in order to define their sensitivity, specificity and accuracy. RESULTS: At the end of the third round, a consensus was reached in 139/210 patients (66.2%). The patients with a consensus ≥80% were classified as confirmed-BD (n = 24), and those with an agreement of 60-79% as probable-BD (n = 10). When comparing these patients with the confounding diseases group, an older age at disease onset, the presence of oral and genital ulcers, skin papulo-pustular lesions, a positive pathergy test and posterior uveitis were BD distinctive elements. The ISG, ICBD and PEDBD criteria were applied to confirmed-BD and to the confounding disease group, showing a sensitivity of 0.50, 0.79 and 0.58, a specificity of 1.00, 0.97, 0.99, and an accuracy of 0.91, 0.94 and 0.92, respectively. CONCLUSIONS: the PEDBD criteria were very specific, while the ICBD resulted to be more sensitive. The complexity of childhood BD suggests larger prospective international cohorts to further evaluate the performance of the criteria.

Efficacy and safety of tofacitinib in patients with rheumatoid arthritis by previous treatment: post hoc analysis of phase II/III trials.

BACKGROUND: This study sought to evaluate the efficacy and safety of tofacitinib in patients with rheumatoid arthritis with distinct treatment histories. METHODS: Pooled phase II/III trial data from patients who received tofacitinib 5 or 10 mg twice daily or placebo, as monotherapy or with conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs), were analyzed post hoc. Separate evaluations were conducted for populations with a prior inadequate response (IR) to: 1) non-methotrexate (MTX) csDMARDs only (non-MTX csDMARD-IR; n = 537); 2) MTX (MTX-IR; n = 3113); and 3) biologic (b)DMARDs (bDMARD-IR; n = 782). Efficacy outcomes included rates of response (American College of Rheumatology 20/50/70% response criteria) and remission (Disease Activity Score in 28 joints derived from 4 measures, erythrocyte sedimentation rate [DAS28-4(ESR)] < 2.6) at month 3, and changes from baseline in DAS28-4(ESR) and Health Assessment Questionnaire-Disability Index scores. Safety was assessed up to month 24. RESULTS: At month 3, efficacy was generally improved with tofacitinib (both doses) vs placebo in each population. Generally, efficacy outcomes with tofacitinib were numerically more favorable in non-MTX csDMARD-IR vs MTX-IR or bDMARD-IR patients. Over 24 months, crude incidence rates for adverse events (AEs), serious AEs, and discontinuations due to AEs were generally numerically lower in non-MTX csDMARD-IR and MTX-IR vs bDMARD-IR populations; rates for AEs of special interest were generally similar across populations. CONCLUSIONS: Tofacitinib provided clinical benefit across patients with rheumatoid arthritis with a range of prior treatment experience but may have greater efficacy and an improved benefit/risk profile in those with fewer prior treatments. TRIAL REGISTRATION: NCT00147498/NCT00413660/NCT00550446/NCT00603512/NCT00687193/NCT00976599/NCT01359150/NCT00847613/NCT00814307/NCT00853385/NCT00960440/NCT01039688/NCT00856544.

5-Fluoro/(trifluoromethoxy)-2-indolinone derivatives with anti-interleukin-1 activity.

The pro-inflammatory cytokine interleukin-1 (IL-1) drives the pathogenesis of several inflammatory diseases. Recent studies have revealed that 2-indolinones can modulate cytokine responses. Therefore, we screened several 2-indolinone derivatives in preliminary studies to develop agents with anti-IL-1 activity. First, the putative efficacies and binding interactions of 2-indolinones were evaluated by docking studies. Second, previously synthesized 5-fluoro/(trifluoromethoxy)-1H-indole-2,3-dione 3-(4-phenylthiosemicarbazones) (compounds 47-69) which had the highest inhibitory effect in the screening were evaluated for inhibitory effects on the IL-1 receptor (IL-1R). Compounds 52 (IC50 = 0.09 µM) and 65 (IC50 = 0.07 µM) were selected as lead compounds for the subsequent synthesis of new derivatives. The novel 5-fluoro/(trifluoromethoxy)-1H-indole-2,3-dione 3-(4-phenylthiosemicarbazones) (compounds 70-116) were designed, synthesized, and in vitro studies were completed. The compounds 76, 78, 81, 91, 100, 105, and 107 tested showed nontoxic inhibitory effects on IL-1R-dependent responses in the range of 0.01-0.06 µM and stronger than the lead compounds 52 and 65. In vitro and in silico findings showed that compounds 78 (IC50 = 0.01 µM) and 81 (IC50 = 0.02 µM) had the strongest IL-1R inhibitory effects and the most favorable drug-like properties. Molecular modeling studies of the compounds 78 and 81 were carried out to determine the possible binding interactions at the active site of the IL-1R.

The correlation between pregnancy, disease activity and adverse pregnancy outcomes in patients with systemic lupus erythematosus.

OBJECTIVE: In this study, our pregnant systemic lupus erythematosus (SLE) cohort, which was under medical surveillance of both our Rheumatology and Obstetrics departments, was analyzed. We intended to determine the effects of pregnancy on disease activity and the correlation between disease flares and adverse pregnancy outcomes. METHODS: One hundred sixty eight pregnancy data involving 136 patients with SLE were examined. Cumulative clinical, laboratory, and serological parameters were described. Disease activity and flares were calculated using the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) in the pre/postpartum periods and the SLEPDAI in the three trimesters of pregnancy. Patients with a SLEDAI-2K or SLEPDAI ≥ 4 were classified as "active." Patients with lupus low disease activity state (LLDAS) during each of these periods were identified.Fetal/neonatal death, premature birth due to pre-eclampsia, eclampsia or hemolysis, elevated Liver enzymes (HELLP) syndrome, and neonates small for gestational age were determined as adverse pregnancy outcomes (APO). RESULTS: Out of 168 pregnancies, there were 60 (35.7%) pregnancies with flares covering the pregnancy and 6 months of postpartum period. The mean SLEDAI in the 6 months postpartum period was significantly higher compared to mean disease activity during pregnancy (p < .05). Of all pregnancies, 132 (78.6%) were in LLDAS during pregnancy. Comparison of the frequency of severe postpartum flares in patients who were in LLDAS during pregnancy revealed a lower percentage of flares compared to those who were not in the LLDAS group (11 vs 29%, p < .05). APO was observed in 33.9% of 168 pregnancies. The mean SLEPDAI score was significantly higher in APO+ pregnancies than in APO- pregnancies (4.9 ± 6.1 vs 2.8 ± 4.9, p = .002). Comparison of SLICC damage score between APO - and + pregnancies revealed a significantly higher score in APO+ pregnancies (1.8 ± 2.1 vs 0.8 ± 1.3, p = .001). CONCLUSION: Postpartum six-month period appears to have the highest risk for disease flares during SLE pregnancies. Disease activity during pregnancy increases the risk of APO. In order to achieve a positive pregnancy outcome and lower maternal morbidity, regular follow-up of patients is necessary.

Effect of aza-BODIPY-photodynamic therapy on the expression of carcinoma-associated genes and cell death mode.

BACKGROUND: Breast cancer is the most common cancer affecting women worldwide.Photodynamic therapy(PDT) has now proven to be a promising form of cancer therapy due to its targeted and low cytotoxicity to healthy cells and tissues.PDT is a technique used to create cell death localized by light after application of a light-sensitive agent.Aza-BODIPY is a promising photosensitizer for use in PDT. Our results showed that aza-BODIPY-PDT induced apoptosis, probably through p53 and caspase3 in MCF-7 cells. Future studies should delineate the molecular mechanisms underlying aza-BODIPY-PDT-induced cell death for a better understanding of the signaling pathways modulated by the therapy so that this novel technology could be implemented in the clinic for treating breast cancer. AIM: In this study,we aimed to determine the change in the expression levels of 88 carcinoma-associated genes induced by aza-BODIPY-PDT were analyzed so as to understand the specific pathways that are modulated by aza-BODIPY-PDT. MATERIAL METHOD: In this study,the molecular basis of the anti-cancer activity of aza-BODIPY-PDT was investigated.Induction of apoptosis and necrosis in MCF-7 breast cancer cells after treatment with aza- BODIPY derivative with phthalonitrile substituents (aza-BODIPY) followed by light exposure was evaluated by Annexin V 7- Aminoactinomycin D (7-AAD) flow cytometry. RESULTS: Aza-BODIPY-PDT induced cell death in MCF-7 cells treated with aza-BODIPY-PDT; flow cytometry revealed that 28 % of the cells died by apoptosis. Seven of the 88 carcinoma-associated genes that were assayed were differentially expressed -EGF, LEF1, WNT1, TCF7, and TGFBR2 were downregulated, and CASP3 and TP53 were upregulated - in cells subjected to aza-BODIPY-PDT.This made us think that the aza-BODIPY-PDT induced caspase 3 and p53-mediated apoptosis in MCF7 cells. CONCLUSION: In our study,it was determined that the application of aza-BODIPY-PDT to MCF7 cells had a negative effect on cell connectivity and cell cycle.The fact that the same effect was not observed in control cells and MCF7 cells in the dark field of aza-BODIPY indicates that aza-BODIPY has a strong phodynamic anticancer effect.

Sluggish cognitive tempo (Cognitive Disengagement Syndrome) symptoms are more associated with a higher risk of internet addiction and internet gaming disorder than ADHD symptoms: A study with medical students and resident doctors.

BACKGROUND & AIMS: The purpose of this study was to examine the relationships between Attention Deficit Hyperactivity Disorder (ADHD), Sluggish Cognitive Tempo (SCT), demographic factors, and Internet Addiction (IA) and internet gaming disorder (IGD) among medical students and resident doctors. METHODS: The study included 274 medical students and resident doctors. (Ages:18-35, 70.4% female). Fisher exact test, Contingency Table analyses, Mann Whithey-U Test and structural equation model-path analysis were used for analysis. The Sociodemographic Information Form, ASRS Scale, Barkley SCT Scale, Young Internet Addiction Test-Short Form and The Digital Game Addiction Scale were utilized to collect data. RESULTS: In the sample, 48 participants (17.51%, 22 female, 26 male) were classified as having a high-risk internet gaming disorder (IGD+), while 53 participants (19.3%, 37 female, 16 male) were classified as having a high-risk internet addiction (IA+). SCT Scale Daydreaming and Sluggishness scores, as well as ASRS Scale Inattention and Hyperactivity/Impulsivity ratings, were all substantially higher in high-risk groups (for all, p < 0.05). Instead of age, there was no difference between high and low-risk groups, but men had a significantly greater rate of high risk- IGD (%32.1 vs. 11.4; p = 0.001). Path analysis revealed that while older age has a substantial negative effect (ß = -0.37, p = 0.001) on increased risk of IA, Inattention (ß = 0.19, p = 0.028), Daydreaming (ß = 0.62, p0.001), and Sluggishness ( ß = 1.12, p0.001) had significant positive effects. On the other hand, results revealed that male gender (ß = 5.08, p0.001), IA scores (ß = 0.21, p0.001), and only Sluggishness ( = 0.52, p = 0.002), but not Inattention, Hyperactivity/impulsivity, or Daydreaming, have positive effects on greater risk of internet gaming disorder (IGD). CONCLUSION & IMPLICATIONS: Our study is the first to show that SCT symptoms increase the risk of Internet addiction and Internet Gaming Disorder even when ADHD symptoms are controlled. To date, many research have highlighted the necessity of ADHD treatment when evaluating IA and IGD. However, SCT symptoms have a greater impact on people who are predisposed to these behavioral addictions, and despite high comorbidity rates, various treatment approaches for ADHD and SCT are effective. SCT should be kept in mind when assessing treatment-resistant individuals with IA and IGD.

Expression and characterization of recombinant IL-1Ra in Aspergillus oryzae as a system.

BACKGROUND: The interleukin-1 receptor antagonist (IL-1Ra) is a crucial molecule that counteracts the effects of interleukin-1 (IL-1) by binding to its receptor. A high concentration of IL-1Ra is required for complete inhibition of IL-1 activity. However, the currently available Escherichia coli-expressed IL-1Ra (E. coli IL-1Ra, Anakinra) has a limited half-life. This study aims to produce a cost-effective, functional IL-1Ra on an industrial scale by expressing it in the pyrG auxotroph Aspergillus oryzae. RESULTS: We purified A. oryzae-expressed IL-1Ra (Asp. IL-1Ra) using ion exchange and size exclusion chromatography (53 mg/L). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that Asp. IL-1Ra is N-glycosylated and approximately 17 kDa in size. We conducted a comparative study of the bioactivity, binding kinetics, and half-life between Asp. IL-1Ra and E. coli IL-1Ra. Asp. IL-1Ra showed good bioactivity even at a low concentration of 0.5 nM. The in vitro half-life of Asp. IL-1Ra was determined for different time points (0, 24, 48, 72, and 96 h) and showed higher stability than E. coli IL-1Ra, despite exhibiting a 100-fold lower binding affinity (2 nM). CONCLUSION: This study reports the production of a functional Asp. IL-1Ra with advantageous stability, without extensive downstream processing. To our knowledge, this is the first report of a recombinant functional and stable IL-1Ra expressed in A. oryzae. Our results suggest that Asp. IL-1Ra has potential for industrial-scale production as a cost-effective alternative to E. coli IL-1Ra.

Facial emotion recognition in adolescent depression: The role of childhood traumas, emotion regulation difficulties, alexithymia and empathy.

Introduction: Facial emotion recognition (FER) is crucial for effective social competency, and problems in this skill are linked depression during adolescence. In this study, we aimed to find the rates of FER accuracy for negative (fearful, sad, angry, disgusted), positive (happy, surprised), and neutral emotions, and the possible predictors of FER skill for most confusing emotions. Subjects and Methods: A total of 67 drug-naive adolescents with depression (11 boys, 56 girls; 11-17 years) were recruited for the study. The facial emotion recognition test, childhood trauma questionnaire and basic empathy, difficulty of emotion regulation, and Toronto alexithymia scales were used. Results: The analysis demonstrated that adolescents have more difficulties in recognizing negative emotions when compared the positive ones. The most confusing emotion is fear (39.8% of fear was recognized as surprise). Boys have lower fear recognition skill than girls and higher childhood emotional abuse, physical abuse, emotional neglect, and difficulty in describing feelings to predict lower fear recognition skill. For sadness recognition skill, emotional neglect, difficulty in describing feelings, and depression severity were the negative predictors. Emotional empathy has a positive effect on disgust recognition skill. Conclusion: Our findings demonstrated that impairment of FER skill for negative emotions is associated with childhood traumas, emotion regulation difficulties, alexithymia, and empathy symptoms in adolescent depression.

Behçet disease, familial Mediterranean fever and MEFV variations: More than just an association.

Behçet disease (BD) and familial Mediterranean fever (FMF) are two inflammatory disorders that share many features including historical background, ethnical distribution and inflammatory characteristics. Several studies suggested that BD and FMF might occur in the same individual more commonly than expected. Additionally, the pathogenic MEFV gene variants, especially p.Met694Val, activating the inflammasome complex have been shown to increase the risk for BD in regions where both FMF and BD are prevalent. Whether these variants are associated with certain disease subtypes and whether they may help in the planning of treatment need to be explored. This review provides a recent overview of the plausible association between FMF and BD and the role of MEFV variants in the pathogenesis of BD.

Synthesis, fabrication and characterization of 2-naphthyloxy group-substituted bis(2-pyridylimino)isoindoline and its derivatives as a positive electrode for vanadium redox flow battery applications.

In recent years, tridentate nitrogen donor ligands have played a vital role in inorganic chemistry. The ease of synthesis, readily modifiable structure and high stability of 1,3-bis(2-pyridylimino)isoindole (BPIs) compounds make them suitable candidates for many potential applications. In this study, a 1,3-bis(2-pyridylimino)isoindoline derivative bearing a naphthoxy unit and its palladium complex (PdBPI) were synthesized and characterized by single crystal X-ray diffraction, NMR, FT-IR, UV-Vis, and mass spectroscopic methods. The BPI- or PdBPI-modified pencil graphite electrodes were clarified via cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), EDX, X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy. The efficiency of these substances in a vanadium redox flow battery (VRB) system was investigated for the first time. The behaviors of the BPI-modified carbon felt electrode (BPI-CF) and PdBPI-modified carbon felt electrode (PdBPI-CF) were investigated in the redox flow battery (RFB) applications. These modified electrodes were obtained by the electrodeposition method. The respective charge potentials of BPI-CF and PdBPI-CF reached 1.63 V and 1.88 V, respectively. The discharge capacity maxima obtained were ∼301 mA h (1204 mA h L-1) and ∼303 mA h (1212 mA h L-1) for BPI-CF and PdBPI-CF at the VRB system under a charge current density of 4.0 mA cm-2 and discharge current density of 0.4 mA cm-2, respectively.

EULAR study group on 'MHC-I-opathy': identifying disease-overarching mechanisms across disciplines and borders.

The 'MHC-I (major histocompatibility complex class I)-opathy' concept describes a family of inflammatory conditions with overlapping clinical manifestations and a strong genetic link to the MHC-I antigen presentation pathway. Classical MHC-I-opathies such as spondyloarthritis, Behçet's disease, psoriasis and birdshot uveitis are widely recognised for their strong association with certain MHC-I alleles and gene variants of the antigen processing aminopeptidases ERAP1 and ERAP2 that implicates altered MHC-I peptide presentation to CD8+T cells in the pathogenesis. Progress in understanding the cause and treatment of these disorders is hampered by patient phenotypic heterogeneity and lack of systematic investigation of the MHC-I pathway.Here, we discuss new insights into the biology of MHC-I-opathies that strongly advocate for disease-overarching and integrated molecular and clinical investigation to decipher underlying disease mechanisms. Because this requires transformative multidisciplinary collaboration, we introduce the EULAR study group on MHC-I-opathies to unite clinical expertise in rheumatology, dermatology and ophthalmology, with fundamental and translational researchers from multiple disciplines such as immunology, genomics and proteomics, alongside patient partners. We prioritise standardisation of disease phenotypes and scientific nomenclature and propose interdisciplinary genetic and translational studies to exploit emerging therapeutic strategies to understand MHC-I-mediated disease mechanisms. These collaborative efforts are required to address outstanding questions in the etiopathogenesis of MHC-I-opathies towards improving patient treatment and prognostication.

Genetic deviation associated with photodynamic therapy in HeLa cell.

Photodynamic therapy (PDT) is a method that is used in cancer treatment. The main therapeutic effect is the production of singlet oxygen (1O2). Phthalocyanines for PDT produce high singlet oxygen with absorbers of about 600-700 nm. AIM: It is aimed to analyze cancer cell pathways by flow cytometry analysis and cancer-related genes with q-PCR device by applying phthalocyanine L1ZnPC, which we use as photosensitizer in photodynamic therapy, in HELA cell line. In this study, we investigate the molecular basis of L1ZnPC's anti-cancer activity. MATERIAL METHOD: The cytotoxic effects of L1ZnPC, a phthalocyanine obtained from our previous study, in HELA cells were evaluated and it was determined that it led to a high rate of death as a result. The result of photodynamic therapy was analyzed using q-PCR. From the data received at the conclusion of this investigation, gene expression values were calculated, and expression levels were assessed using the 2-∆∆Ct method to examine the relative changes in these values. Cell death pathways were interpreted with the FLOW cytometer device. One-Way Analysis of Variance (ANOVA) and the Tukey-Kramer Multiple Comparison Test with Post-hoc Test were used for the statistical analysis. CONCLUSION: In our study, it was observed that HELA cancer cells underwent apoptosis at a rate of 80% with drug application plus photodynamic therapy by flow cytometry method. According to q-PCR results, CT values ​​of eight out of eighty-four genes were found to be significant and their association with cancer was evaluated. L1ZnPC is a new phthalocyanine used in this study and our findings should be supported by further studies. For this reason, different analyses are needed to be performed with this drug in different cancer cell lines. In conclusion, according to our results, this drug looks promising but still needs to be analyzed through new studies. It is necessary to examine in detail which signaling pathways they use and their mechanism of action. For this, additional experiments are required.

Criteria for Hyperinflammation Developing in COVID-19: Analysis of 2 Cohorts From Different Periods of the Pandemic.

OBJECTIVE: Hyperinflammation (HI) that develops in week 2 of COVID-19 contributes to a worse outcome. Because week 2 laboratory findings can be relatively mild, the available criteria for classification of hemophagocytic lymphohistiocytosis or macrophage activation syndrome are not helpful. METHODS: Our study included a discovery cohort of patients from Turkey with symptomatic COVID-19 who were followed up while hospitalized during the initial wave and a replication cohort of hospitalized patients from a later period, all of whom required oxygen support and received glucocorticoids. Diagnosis of HI was made by an expert panel; most patients with COVID-19-associated HI (HIC) received tocilizumab or anakinra. Clinical and laboratory data from start day of treatment with tocilizumab or anakinra in HIC patients were compared with the data from day 5-6 in patients without HIC. Values maximizing the sensitivity and specificity of each parameter were calculated to determine criteria items. RESULTS: The discovery cohort included 685 patients, and the replication cohort included 156 patients, with 150 and 61 patients receiving treatment for HI, respectively. Mortality rate in HI patients in the discovery cohort (23.3%) was higher than the rate in patients without HI (3.7%) and the rate in patients in the overall replication cohort (10.3%). The 12-item criteria that we developed for HIC showed that a score of 35 provided 85.3% sensitivity and 81.7% specificity for identification of HIC. In the replication cohort, the same criteria resulted in 90.0% sensitivity for HIC; however, lower specificity values were observed because of the inclusion of milder cases of HIC responding only to glucocorticoids. CONCLUSION: The use of the 12-item criteria for HIC can better define patients with HIC with reasonable sensitivity and specificity and enables an earlier treatment start.

Efficacy and safety of interleukin-1 blockers in kidney transplant recipients with familial Mediterranean fever: a propensity score-matched cohort study.

BACKGROUND: Data on use of interleukin (IL)-1 blockers in kidney transplant recipients (KTRs) with familial Mediterranean fever (FMF) are very limited. We aimed to evaluate the efficacy and safety of anakinra and canakinumab in the transplantation setting. METHODS: In this retrospective cohort study, we included KTRs who suffered from AA amyloidosis caused by FMF and treated with anakinra or canakinumab (study group, n = 36). Using propensity score matching, we selected 36 patients without FMF or amyloidosis from our database of 696 KTRs as the control group. Primary outcomes were patient and graft survival. Biopsy-confirmed graft rejection, changes in estimated glomerular filtration rate (eGFR), high-sensitivity CRP (hsCRP), erythrocyte sedimentation rate (ESR), proteinuria and number of monthly attacks were secondary outcomes. RESULTS: All KTRs with FMF began IL-1 blocker therapy with anakinra and nine (25%) were switched to canakinumab. Overall death was more frequent in the study group (19.4% vs 0%) (P = .005); however, overall graft loss was comparable between study (27.8%) and control groups (36.1%) (P = .448). Five- and 10-year graft survival rates were significantly higher in the study group (94.4% and 83.3%, respectively) than in the control group (77.8% and 63.9%, respectively) (P = .014 and P < .001, respectively). Rejections were numerically lower in study group (8.3% vs 25%), but it did not reach to statistical significance (P = .058). When compared with the pre-treatment period, with IL-1 blockers, the number of attacks per month (P < .001), and eGFR (P = .004), hsCRP (P < .001) and ESR (P = .026) levels were lower throughout the follow-up, whereas proteinuria levels were not. CONCLUSIONS: Anakinra and canakinumab are effective in KTRs suffering from FMF; however, the mortality rate may be of concern.

Treat to target in Behcet's disease: Should we follow the paradigm of other systemic rheumatic diseases?

During the last decades the efficacy of biologic agents, mainly of anti-TNFs, in controlling the activity of serious manifestations of Behcet's Disease (BD) has been established. On the other hand, the clinical heterogeneity of BD has precluded the validation of a widely-accepted composite index for disease assessment and for target disease-state definitions, such as low disease activity and remission, and the testing of their implementation in clinical practice. Therefore, in contrast to other systemic rheumatic diseases, a treat-to-target strategy has not yet been developed in BD. There are several challenges towards this approach, including standardization of outcome measures for assessing the disease activity in each-affected organ and construction of a composite disease activity index. The challenges for the development of a treat-to-target strategy and possible solutions are discussed in this position paper, which stemmed from a round table discussion that took place in the 19th International Conference on BD.