The ameliorative effects of cannabidiol on methotrexate-induced neuroinflammation and neuronal apoptosis via inhibiting endoplasmic reticulum and mitochondrial stress.

Methotrexate (MTX) is an antineoplastic agent and has neurotoxic effects. It exerts its toxic effect on the brain by triggering inflammation and apoptosis. Cannabidiol (CBD) is an agent known for its antioxidant, anti-inflammatory effects in various tissues. The aim of this study is to examine the protective effects of CBD treatment in various brain structures from MTX damage and to evaluate the effect of intracellular pathways involved in apoptosis. Thirty-two adult Wistar Albino female rats were divided into four groups as control, MTX (20 mg/kg intraperitoneally [i.p.]), MTX + CBD (0.1 mL of 5 mg/kg i.p.), and CBD (for 7 days, i.p.). At the end of the experiment, brain tissues collected for biochemical analyses as total oxidant status (TOS), total antioxidant status, oxidative stress index (OSI), histopathological and immunohistochemical analyses as tumor necrosis factor-α (TNF-α), serotonin, mammalian target of rapamycin (mTOR) staining, genetic analyses as caspase-9 (Cas-9), caspase-12 (Cas-12), C/EBP homologous protein (CHOP), and cytochrome-c (Cyt-c) gene expressions. In the histopathological and immunohistochemical evaluation, hyperemia, microhemorrhage, neuronal loss, and significant decreasing expressions of seratonin were observed in the cortex, hippocampus, and cerebellum regions in the MTX group. mTOR, TNF-α, Cas-9, Cas-12, CHOP, and Cyt-c expressions with TOS and OSI levels were increased in the cortex. It was observed that these findings were reversed after CBD application in all regions. MTX triggers neuronal apoptosis via endoplasmic reticulum and mitochondrial stress while destroying serotonergic neurons. The reversal of the pathological changes with CBD treatment proves that it has anti-inflammatory and antiapoptotic activity in brain.

When should the use of biological agents be considered in persistent oligoarticular juvenile idiopathic arthritis patients?

The purpose of this study was to compare the demographic and clinical characteristics of the groups with and without bDMARDs added to the treatment of persistent oligoarticular juvenile idiopathic arthritis (JIA) patients on methotrexate (MTX) and also to determine the predictors of adding bDMARDs to treatment. This study included 86 oligoarticular JIA patients on MTX. Patients were divided into two groups receiving MTX (n = 69) and MTX plus bDMARD (n = 17). Predictors of adding bDMARDs were investigated by comparing demographic, clinical features and laboratory findings. Gender, age at diagnosis, time elapsed from the onset of symptoms to diagnosis, and disease duration, the number and distribution of affected joint at the time of diagnosis were similar in both groups. The mean JADAS10 at the time of diagnosis were 18.8 ± 4.2 and 19.5 ± 6.4 in the MTX and MTX plus bDMARDs groups, respectively (p = 0.68). JADAS10 at 3rd and 6th month were significantly higher in patients on MTX plus bDMARDs (p = 0.001, p = 0.004, respectively). In multivariate analysis, the risk of adding bDMARD was shown to increase 1.24-fold (p = 0.004, 95% CI: 1.07-1.43) for each point increase on the JADAS 10 at 3rd months. The number (p = 0.64) or type (p = 0.18) of joint involvement at disease onset were not predictors of adding a bDMARD. CONCLUSION: JADAS10 indicating ongoing severe disease activity at 3rd and 6th months rather than baseline JADAS10 is associated with the addition of bDMARDs. WHAT IS KNOWN: • Oligoarticular JIA patients have the best outcomes among JIA categories and respond favorably to first-line therapies such as non-steroidal anti-inflammatory drugs and intraarticular corticosteroid injections. • Clinically inactive disease rates have increased with the widespread use of biological agents in oligoarticular JIA patients who have not responded to initial therapies. WHAT IS NEW: • Approximately one-fifth of patients with persistent oligoarticular JIA on methotrexate may require the addition of a biological disease modifying anti-rheumatic drug during follow-up. • The JADAS10 calculated at 3 and 6 months is a valuable tool to identify patients who should be added biological disease modifying anti-rheumatic drugs in persistent oligoarticular JIA.

Rheumatoid Arthritis-Related Lung Disease and Its Association With Mortality.

PURPOSE: The aim of this study was to determine the association of rheumatoid arthritis-related lung disease (RA-LD) and its subtypes with all-cause mortality. MATERIALS AND METHODS: For the present analyses, patients with RA who underwent computed tomography of the chest (chest-CT) were evaluated. RA-LD was defined in 4 subtypes as follows: interstitial lung disease (RA-ILD), airway disease (RA-AD), rheumatoid pulmonary nodules (RA-PN), and RA-related pleural disease (RA-PD). The date of RA-LD diagnosis was considered the date of the first chest-CT detecting the pathology. To assess the factors associated with mortality, multivariable logistic regression analyses were performed with variables selected based on their causal associations with the outcome. RESULTS: Of 576 RA patients, 253 (43.9%) had RA-LD (38.7% male; mean age at RA-LD diagnosis, 59.9 ± 9.8 years). The most common subtype was RA-AD, which was detected in 119 (47.0%) patients followed by 107 (42.3%) with RA-ILD, 70 (27.7%) with RA-PN, and 31 (12.3%) with RA-PD. Sixty-one (24.1%) patients had 2+ subtypes. After median follow-up of 10.2 years, 97 (16.8%) died. The existence of at least 1 subtype and 2+ subtypes increased the all-cause mortality, as indicated by odds ratios of 1.60 (95% confidence interval [CI], 1.03-2.48) and 2.39 (95% CI, 1.26-4.54), respectively. Among RA-LD patients, RA-ILD and RA-PD were associated with increased mortality (odds ratios were 2.20 [95% CI, 1.18-4.08] and 1.62 [95% CI, 0.70-3.75], respectively). CONCLUSIONS: In this study, RA-AD was the most common subtype, and the presence of RA-LD increased mortality. This effect was particularly pronounced in patients with RA-ILD and RA-PD or those presenting with 2+ subtypes.

Assessment of quality of life, school performance, and physical activity in adolescents with Familial Mediterranean fever.

OBJECTIVES: The aim of this study is to evaluate differences in school performance, school attendance, quality of life, and physical activity in adolescents with Familial Mediterranean fever (FMF) compared to healthy controls. METHODS: One hundred and twenty-nine patients with FMF and 154 healthy controls between 13 and 18 years were included in the study. Demographic, school performance (according to grade point average), school absenteeism, and type and frequency of exercise were recorded. Quality of life was evaluated with the Pediatric Quality of Life Inventory (PedsQL) 4.0. RESULTS: The mean age of FMF patients was 15.1 ± 2.7 years, and 69 patients (53.5%) were female. School performance was significantly higher in the control group compared to FMF patients (P < 0.001). In the control group, there were significantly higher participants who engaged in professional sports (P < 0.001). Patients with FMF had significantly lower self-reported PedsQL scores in school functioning, physical, and psychosocial health domains compared to those in the control group (P = 0.001, P < 0.001, and P = 0.028, respectively). CONCLUSIONS: FMF patients demonstrated lower school performance and quality-of-life scores compared to healthy controls. In addition to improving symptoms in chronic diseases, it is important to evaluate and improve the quality of life of patients in routine practice and to ensure psychosocial well-being.

The Juvenile Spondyloarthritis Disease Activity Index Is a Useful Tool in Enthesitis-Related Arthritis: Real-Life Data.

OBJECTIVE: To compare enthesitis-related arthritis (ERA) patients with active and inactive disease at 6 months and define baseline predictors for disease inactivity. In addition, to evaluate the demographic, clinical, and laboratory characteristics of ERA patients and to identify the real-life impact of the Juvenile Spondyloarthritis Disease Activity Index (JSpADA) in predicting active disease in ERA. METHODS: This medical record review study was conducted with 56 patients who were diagnosed with ERA at our clinic between June 2009 and June 2022. Demographic and clinical characteristics, laboratory parameters, treatment, and JSpADA were recorded. RESULTS: The patients were divided into 2 groups as active (n = 34) and inactive (n = 22) according to their disease activity at month six. Sex, age at diagnosis, number and type of affected joints, and presence of sacroiliitis were similar in both groups. There was no difference in baseline erythrocyte sedimentation rate, but there was a significant difference in erythrocyte sedimentation rate at the third month ( p = 0.52 and p = 0.018, respectively). The median JSpADA values at disease onset were 3.5 (interquartile range [IQR], 3.0-4.5) and 3.3 (IQR, 2.5-4.0) in the active and inactive groups, respectively ( p = 0.27). At the third month, the median JSpADA values were 1.5 (IQR, 0.5-2.1) in the active group and 0.5 (IQR, 0.5-1.5) in the inactive group ( p = 0.037). The cutoff value for JSpADA at the third month for active disease persisting at the month six was determined as 1 point (area under the curve, 0.662 ± 0.06; p = 0.042; 95% confidence interval, 0.51-0.80) by receiver operating characteristic curve analysis. CONCLUSION: In ERA patients, a persistently high JSpADA value at follow-up is a predictive factor for active disease at the sixth month.

Frequency of Helicobacter pylori in Patients With Rheumatoid Arthritis Whose Methotrexate Was Stopped Due to Gastrointestinal Intolerance.

OBJECTIVE: The aims of this study were to compare the frequency of Helicobacter pylori between patients with rheumatoid arthritis (RA) with and without methotrexate (MTX)-related gastrointestinal system (GIS) intolerance, and to demonstrate the associated factors with such intolerance. METHODS: The data of 9756 patients with RA who presented between January 2011 and December 2020 were evaluated. Methotrexate-related GIS intolerance was defined as the discontinuation of MTX owing to the dyspeptic symptoms despite supportive measures and was detected in 1742 (31.3%) patients among 5572 MTX users. A total of 390 patients with and without intolerance who had at least 1 gastroscopic evaluation were included in the final analyses. The demographic, clinical, laboratory, and pathologic characteristics of patients with and without MTX-related GIS intolerance were compared. To determine the associated factors with MTX-related GIS intolerance, logistic regression analysis was performed. RESULTS: Of 390 patients, 160 (41.0%) patients had MTX-related GIS intolerance. According to the pathology results, the presence of H. pylori , inflammation, and activity were significantly higher in patients with MTX-related GIS intolerance ( p < 0.001 for each comparison). In multivariable logistic regression analysis, the use of biologic disease-modifying antirheumatic drugs (DMARDs) or targeted synthetic DMARDs was found to be an independently associated factor for MTX-related GIS intolerance (odds ratio [OR], 3.03 for model 1; OR, 3.02 for model 2) in addition to H. pylori presence (OR, 9.13 for model 1; OR, 5.71 for model 2). CONCLUSIONS: In this study, we found that the presence of H. pylori and the use of biologic or targeted synthetic DMARDs were associated with MTX-related GIS intolerance.

Can Subclinical Atherosclerosis Be Assessed More Precisely in Behçet Syndrome Patients by Using a Particular Cutoff Value for Carotid Intima Media Thickness?

OBJECTIVE: Behçet syndrome (BS) is a multisystemic chronic vasculitic disease. Among previous studies, although there are some that showed increased risk of subclinical atherosclerosis in BS, there are also others that showed the opposite. The objective of this study is to evaluate subclinical atherosclerosis in BS by using the cutoff value for intima-media thickness in the 2013 European Society of Cardiology/European Society of Hypertension guideline. METHODS: We conducted a cross-sectional analysis of 100 BS patients and 30 healthy volunteers at a single center in a 4-month period. All ultrasound scans were performed in a blind manner to the clinical assessment, and they were carried out by the same researcher by a B-mode ultrasonography. RESULT: When we grouped the patients based on the presence of subclinical atherosclerosis, the frequency of subclinical atherosclerosis in the BS patients was found to be higher than that in the healthy controls (32% and 7%, respectively; p = 0.006). When a cutoff is used for carotid intima-media thickness, increased atherosclerosis risk is observed in BS patients with vascular involvement (p = 0.043). CONCLUSIONS: Although higher inflammation and increased atherosclerosis in vascular BS patients were expected, this situation was not supported much in previous studies. We think that this may have been caused by mere comparison of numerical data, and usage of a cutoff value could be more significant in distinguishing what is normal and what is abnormal as in several medical parameters.

Causes of severe infections in patients with systemic sclerosis and associated factors.

BACKGROUND: Systemic sclerosis (SSc) is a chronic systemic disease characterized by vascular damage, autoimmunity, and fibrosis in the skin and internal organs. In this study, we tried to determine the causes of severe infection in patients with SSc and to reveal the factors associated with severe infection. METHODS: We retrospectively examined 214 SSc patients between January 2010 and August 2020. Forty-seven patients with at least one severe infection and 167 patients without severe infection were compared. RESULTS: A total of 76 episodes of severe infections were detected in 47 (22%) patients. Common infections included pneumonia, infected digital ulcer, urinary tract infections, and osteomyelitis. Female patients had a higher frequency in the group without severe infection (91.6% vs. 80.9%, p = 0.035). Patients with severe infections had a higher frequency of digital ulcers (p < 0.001), cardiac (p = 0.002), and GIS involvement (p < 0.001). In multivariable analysis, digital ulcer presence (OR: 2.849 [1.356-5.898] (p = 0.006) and cardiac involvement (OR: 2.801 [1.248-6.285]) were associated with severe infection. Of the patients with severe infections, 34% had recurrent severe infections. There was no difference in demographic and clinical characteristics between patients with recurrent and nonrecurrent severe infections. DISCUSSION: The presence of digital ulcer and cardiac involvement seem to be associated with a severe infection in patients with systemic sclerosis. In patients with cardiac involvement and digital ulcers, more careful attention may be required for the development of severe infections.

High mobility group box-1 levels may be associated with disease activity of Behcet's disease

BACKGROUND: High mobility group box- 1 (HMGB- 1) is a nuclear protein acting as a proinflammatory molecule. The serum HMGB- 1 levels were found elevated in chronic inflammatory diseases. In this cross-sectional study, serum HMGB- 1 levels in Behcet's disease (BD) patients and healthy controls (HC) were studied. Also, its association with disease activity scores and clinical findings were evaluated. METHODS: Ninety BD patients and 50 age-sex matched HC were included in the study. Disease activity scores were assessed by Behcet Disease Current Activity Form (BDCAF) and Behcet Syndrome Activity Score (BSAS). Serum HMGB- 1 levels were measured using a commercial ELISA kit. A p value of < 0.05 was considered to be statistically significant. RESULTS: Serum HMGB- 1 levels were significantly higher in BD than in HC (43.26 pg/mL and 16.73 pg/mL; p < 0.001, respectively). Serum HMGB- 1 levels were statistically significantly associated with presence of erythema nodosum (EN) and genital ulcers in the last one month prior to recruitment (p = 0.041 and p < 0.001, respectively). BDCAF and BSAS scores were positively correlated with serum HMGB- 1 level ( p = 0.03 and p = 0.02, respectively). DISCUSSION: HMGB - 1 may play a role in the development of BD. Also, due to its positive correlation with disease activity indices, it can be used as a novel disease activity parameter in BD.

Serum Interleukin 35 Levels in Systemic Sclerosis and Relationship With Clinical Features.

BACKGROUND/OBJECTIVE: Interleukin (IL) 35 is a member of the IL-12 family. Studies show that IL-35 is an important anti-inflammatory cytokine and suppresses effector T-cell activity. In this study, we aimed to evaluate serum IL-35 levels in systemic sclerosis (SSc) patients and its potential relation with clinical findings. METHODS: We conducted a cross-sectional analysis of 70 SSc patients and 29 healthy volunteers in a single center in 5 months' period. Extension of skin fibrosis was evaluated by using modified Rodnan skin score. Disease severity was assessed by Medsger disease severity scores. Serum IL-35 was measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit (Cloud-Clone Corp, Wuhan, China). The relationship between IL-35 levels and clinical and laboratory parameters was investigated. Mann-Whitney U test was used to compare parameters among the groups. Correlation was tested by Spearsman correlation coefficient. RESULTS: Serum IL-35 levels was significantly higher in SSc patients (8.69 [interquartile range, 29.33] pg/mL) than in healthy controls (7.11 [interquartile range 7.53] pg/mL; p < 0.001). There was no significant relationship between serum IL-35 levels and organ involvement. There was a negative correlation between serum IL-35 levels and Medsger disease severity score (Rho, -0.333; p = 0.006), modified Rodnan skin score (Rho, -0.307; p = 0.010), and C-reactive protein (Rho, -0.294; p = 0.015). There was no relationship between IL-35 and disease duration and erythrocyte sedimentation rate. CONCLUSIONS: Our study revealed that IL-35 levels were higher in SSc patients, and in contrast to previous studies, it was the first study that showed that IL-35 levels did not increase in SSc patients with pulmonary fibrosis.

Process optimisation, biocompatibility and anti-cancer efficacy of curcumin loaded gelatine microparticles cross-linked with dialdeyhde carboxymethyl cellulose.

In this study, we produced curcumin loaded gelatine microparticles, through spray-drying method, with dialdehyde carboxymethyl cellulose (DCMC) which is introduced as a new cross-linking agent for drug delivery systems and examined toxicities by comparison of traditional cross-linking agents. We employed various parameters in the production and tried to develop the most efficient drug delivery system through Taguchi method by examining efficiencies on gastric cancer under in vitro conditions. The results indicated gelatine microparticles cross-linked with DCMC offers more biocompatible drug delivery systems. The particle size of the microparticles produced via different parameters varies from 1.926 to 3.357 µm. Curcumin was substantially remained stable after 6 months. This study indicates potential use of DCMC cross-linked gelatine microparticles as drug delivery vehicle.

Zero valent zinc nanoparticles promote neuroglial cell proliferation: A biodegradable and conductive filler candidate for nerve regeneration.

Regeneration of nerve, which has limited ability to undergo self-healing, is one of the most challenging areas in the field of tissue engineering. Regarding materials used in neuroregeneration, there is a recent trend toward electrically conductive materials. It has been emphasized that the capacity of conductive materials to regenerate such tissue having limited self-healing ability improves their clinical utility. However, there have been concerns about the safety of materials or fillers used for conductance due to their lack of degradability. Here, we attempt to use poly(Ɛ-caprolactone) (PCL) matrix consisting of varying proportions of zero valent zinc nanoparticles (Zn NPs) via electrospinning. These conductive, biodegradable, and bioactive materials efficiently promoted neuroglial cell proliferation depending on the amount of Zn NPs present in the PCL matrix. Chemical characterizations indicated that the incorporated Zn NPs do not interact with the PCL matrix chemically and that the Zn NPs improved the tensile properties of the PCL matrix. All composites exhibited linear conductivity under in vitro conditions. In vitro cell culture studies were performed to determine the cytotoxicity and proliferative efficiency of materials containing different proportions of Zn NPs. The results were obtained to explore new conductive fillers that can promote tissue regeneration.

Polyacrylamide-based semi-interpenetrating networks for entrapment of laccase and their use in azo dye decolorization.

In this study, laccase from Trametes versicolor was immobilized in poly(acrylamide-crotonic acid)/sodium alginate [P(AAm-CrA)/alginate], poly(acrylamide-crotonic acid)/K-carrageenan [(P(AAm-CrA)/K-car)], poly(acrylamide-citraconic acid)/sodium alginate (P(AAm-CA)/alginate), and poly(acrylamide-citraconic acid)/K-carrageenan (P(AAm-CA)/K-car) semi-interpenetrating network by entrapment method. Optimum pH and temperatures values were determined between 5.0-6.0 and 40-50 °C for free laccase (FL) and immobilized laccases, respectively. After 42 days of storage at 4 °C, FL and immobilized laccases retained their original activities in the range of 55%-73%. Percent decolorization of Acid Orange 52 by free enyzme and enyzmes immobilized in hydrogels was found between 63% and 39%. Percent decolorization of Acid Orange 52 in the presence of mediator by free enyzme was found 73% and enyzmes immobilized in hydrogels were found as 73%.

A novel insight into the neuroprotective effects of cannabidiol: maintained apelin/dopamine synthesis, NRF2 signaling, and AKT/CREB/BDNF gene expressions.

Neuroinflammation is a process associated with degeneration and loss of neurons in different parts of the brain. The most important damage mechanisms in its formation are oxidative stress and inflammation. This study aimed to investigate the protective effects of cannabidiol (CBD) against neuroinflammation through various mechanisms. Thirty­two female rats were randomly divided into 4 groups as control, lipopolysaccharide (LPS), LPS + CBD and CBD groups. After six hours following LPS administration, rats were sacrificed, brain and cerebellum tissues were obtained. Tissues were stained with hematoxylin­eosin for histopathological analysis. Apelin and tyrosine hydroxylase synthesis were determined immunohistochemically. Total oxidant status and total antioxidant status levels were measured, and an oxidative stress index was calculated. Protein kinase B (AKT), brain-derived neurotrophic factor (BDNF), cyclic­AMP response element­binding protein (CREB) and nuclear factor erythroid 2­related factor 2 (NRF2) mRNA expression levels were also determined. In the LPS group, hyperemia, degeneration, loss of neurons and gliosis were seen in all three tissues. Additionally, Purkinje cell loss in the cerebellum, as well as neuronal loss in the cerebral cortex and hippocampus, were found throughout the LPS group. The expressions of AKT, BDNF, CREB and NRF2, apelin and tyrosine hydroxylase synthesis all decreased significantly. CBD treatment reversed these changes and ameliorated oxidative stress parameters. CBD showed protective effects against neuroinflammation via regulating AKT, CREB, BDNF expressions, NRF2 signaling, apelin and tyrosine hydroxylase synthesis.

The factors predicting development of serious infections in ANCA-associated vasculitis.

BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare autoimmune disease usually involving small vessels and progressing with necrotizing inflammation. Treatment requires long-term use of immunosuppressive agents to inhibit disease activity. Serious infections (SIs) are a common complication in AAV. OBJECTIVE: The aim of this study was to identify the risk factors for serious infections which required hospitalization in patients with AAV. METHODS: In this retrospective cohort study., we included 84 patients admitted to the Ankara University Faculty of Medicine in the last 10 years with a diagnosis of AAV. RESULTS: In 42 (50%) of 84 patients followed up with the diagnosis of AAV, an infection requiring hospitalization was identified. The patients' total corticosteroid dose, use of pulse steroids, induction regimen, levels of C-reactive protein (CRP) and the presence of pulmonary and renopulmonary involvement were found to be associated with the frequency of infection (p=0.015, p=0.016, p=0.010, p=0.03, p= 0.026 and p=0.029, respectively). In multivariable analysis, it was found that renopulmonary involvement (p=0.002, HR=4.95, 95% CI= 1.804-13.605), age of over 65 (p=0.049, HR=3.37, 95% CI=1.004-11.369) and high CRP levels (p=0.043, HR=1.006, 95% CI=1.000-1.011) constituted independent predictors of serious infection risk. CONCLUSION: The frequency of infection is known to be increased in ANCA-associated vasculitis. Our study showed that renopulmonary involvement, age and elevated CRP levels on admission are independent risk factors of infection.

Synthesis and biological evaluation of optically active conjugated γ- and δ-lactone derivatives.

An efficient synthesis of racemic and both enantiomeric forms of heteroaryl substituted γ- and δ-lactone derivatives derived from allyl and homoallyl alcohol backbones has been accomplished via ring closing metathesis reaction. 2-Heteroaryl substituted allyl and homoallyl alcohols have been efficiently resolved through enzymatic method with high ee (97-99%) and known stereochemistry. Antimicrobial and antioxidant activities of target lactones were evaluated.

Systemic Immune Inflammation Index as a Reliable Disease Activity Marker in Psoriatic Arthritis.

OBJECTIVE: To assess the utility of systemic immune inflammation index (SII) in predicting disease activity in psoriatic arthritis (PsA) patients. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Diskapi Yildirim Beyazit Research and Training Hospital, Ankara, Turkey, from October 2020 to September 2021. METHODOLOGY: This study included 106 PsA and 103 age and gender-matched healthy individuals. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), and SII were calculated from complete blood count parameters. The PsA disease activity was assessed by using disease activity score-ESR and DAS-CRP based on 28 joints and the Disease Activity in Psoriatic Arthritis (DAPSA) scores. The receiver operating characteristic (ROC) curve was performed to evaluate the utility of SII in determining disease activity in PsA patients. RESULTS: The NLR, PLR, MLR, and SII were significantly higher in PsA patients compared to healthy control (p=0.013, p=0.019, p=0.012, and p=0.002, respectively). There were statistically significant positive correlations between the DAS28-ESR, DAS28-CRP, and DAPSA and SII (p<0.001, p<0.001, and p<0.001 respectively). The SII values were significantly higher in PsA patients with moderate to severe disease activity according to DAPSA scores when compared to patients with remission or low disease activity (p<0.001). The cut-off value of 800x109/L was found for predicting disease activity in PsA. CONCLUSION: SII may be an easy, practical, economical, and readily accessible tool for monitoring disease activity and the efficacy of treatment in PsA patients. KEY WORDS: Blood cell count, Psoriatic arthritis, Systematic immune inflammation index (SII).

Disseminated Nocardiosis with Ocular Involvement in a Patient with Anca-associated Vasculitis.

A 62-year male patient, diagnosed with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), developed proptosis and decrease in visual acuity while on rituximab treatment. As the ophthalmological examination and imaging studies could not exclude tumour of the orbit, enucleation of the orbit was performed. The histopathology displayed necrosis and inflammation. Because the clinical, laboratory and pathological findings of the patient suggested a vasculitis exacerbation, the immunosuppressive treatment was continued. However, the patient developed confusion and hemiplegia with cerebral mass lesions on imaging. The subsequent report of the pathology revealed a nocardial infection of the eye. The patient was diagnosed with nocardiosis with ocular and cerebral involvement. Despite efficient antimicrobial therapy, the disease progressed rapidly causing death. This case is unique as it describes disseminated nocardiosis with ocular and cerebral involvement in an AVV patient. Key Words: Immunosuppression, Nocardiosis, ANCA-associated vasculitis, Proptosis.

Biochemical, pharmacological, and toxicological attributes of caper (Capparis ovata) flowering buds and berries pickles.

Capparis ovata is a natural plant that grows widely in Turkey and its flowering buds and berry pickle are used in traditional medicine. Thus, the current study was expanded to evaluate the biochemical, pharmacological, and toxicological aspects of the Capparis ovata water extract (COWE). To determine the biochemical properties of COWE, mineral and fatty acid content, elemental analysis, flavonoid/phenolic content, radical-scavenging capacity, and pesticide analysis were performed. Furthermore, to find out whether it had anti-inflammatory properties, reverse transcription-polymerase chain reaction (RT-PCR) and nuclear factor kappa B (NF-κB) luciferase activity tests were conducted. Whole-genome transcriptomic profiling was carried out at a dose level of 500 mg/kg COWE to understand its pharmacological effect. Transaminases in serum were tested, and quantitative polymerase chain reaction (qPCR) was done using a custom design array that included the stress and molecular toxicology pathway to establish its toxicological qualities. As a result of the evaluations, it was observed that COWE has a high mineral and unsaturated fatty acid content, flavonoid/phenolic content, and radical-scavenging ability. It significantly inhibited NF-κB transcriptional activity as well as inflammatory cytokine expression in T-lymphoblast cells. Whole-genome transcriptomic profiling depicted that COWE modulates immune responses by upregulating natural killer cell activation, cellular response to type I interferon, B-cell proliferation and differentiation, and Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways. Molecular Toxicology Pathfinder RT2 Profiler PCR array analysis revealed that COWE at or lower dose of 500 mg/kg/day did not cause a comparatively adverse effect. According to the findings, COWE is a rich source of nutrients and can be used as an adjunct therapy for various inflammatory diseases.

Prognostic factors for relapse and poor outcome in neuro-Behçet's syndrome: results from a clinical long-term follow-up of a single centre.

OBJECTIVE: To describe the clinical characteristics of neuro-Behçet's syndrome (NBS) and to define the factors associated with relapses and poor outcome. METHODS: Among 2118 patients with Behçet's syndrome who fulfilled the international study group criteria, 208 (9.8%) patients had NBS. Retrospective data of 125 NBS patients (55.5% male; mean age 37.2 ± 11.8 years) were analysed. We divided patients into two subgroups, either parenchymal (p-NBS) or non-parenchymal (np-NBS), according to international consensus recommendations for NBS. We assessed the predictor factors associated with relapse and poor outcome-which was defined as a modified Rankin score (mRS) ≥ 3 at last follow-up and/or death-using Cox and logistic regression analyses, respectively. RESULTS: In total, 79 (63.2%) patients presented with p-NBS and 46 (36.8%) presented with np-NBS. Ocular involvement was more common in p-NBS than np-NBS (55.7% vs. 37.0%, p = 0.04), whereas vascular involvement excluding cerebral vein thrombosis was more frequent in patients with np-NBS (19.0% vs. 52.2%, p < 0.001). Forty-two patients (33.6%) experienced at least one relapse. Factors associated with relapse were BS diagnosis at a younger age and cranial nerve dysfunction (HR 0.96 95% CI 0.93-0.99 and 2.36 95% CI 1.23-4.52, respectively). After a median of 68 (Q1-Q3: 25-125) months, 23 patients (18.4%) had a poor outcome. Indicators of a poor outcome were higher initial mRS and the progressive p-NBS type (OR 8.28 95% CI 1.04-66.20 and 33.57 95% CI 5.99-188.21, respectively). CONCLUSION: Our findings indicate that clinical characteristics and prognosis differ between NBS subgroups, of which patients with p-NBS have worse outcomes.