Twenty Years of SPARTAN: From Inception to Impact (SPARTAN 2023 Annual Meeting Proceedings).

PURPOSE OF REVIEW: This review takes a look at the past, present, and future of SPARTAN, the Spondyloarthritis Research and Treatment Network, an organization of North American healthcare professionals dedicated to advancing research, education, and patient care in spondyloarthritis. RECENT FINDINGS: In 2022, SPARTAN completed the Classification of Axial SpondyloarthritiS Inception Cohort (CLASSIC) study, a collaboration with the Assessment in SpondyloArthritis International Society (ASAS). CLASSIC aimed to validate the 2009 ASAS classification criteria for axial spondyloarthritis. Other ongoing SPARTAN endeavors include the development of US referral recommendations for axial spondyloarthritis, an update of the 2019 ACR/SAA/SPARTAN treatment recommendations for axial spondyloarthritis and multiple educational initiatives. Twenty years after its inception, SPARTAN continues to grow and broaden its impact, guided by the SPARTAN vision of "a world free of spondyloarthritis through leadership in research and education."

DFT, Molecular Docking, ADME, and Cardiotoxicity Studies of Persuasive Thiazoles as Potential Inhibitors of the Main Protease of SARS-CoV-2.

This study explores the capability of thiazoles as potent inhibitors of SARS-CoV-2 Mpro. Seventeen thiazoles (1-17) were screened for their linking affinity with the active site of SARS-CoV-2 Mpro and compared with the FDA-recommended antiviral drugs, Remdesivir and Baricitinib. Density Functional Theory (DFT) calculations provided electronic and energetic properties of these ligands, shedding light on their stability and reactivity. Molecular docking analysis revealed that thiazole derivatives exhibited favorable linking affinities with various functional sites of SARS-CoV-2 proteins, including spike receptor-linking zone, nucleocapsid protein N-terminal RNA linking zone, and Mpro. Notably, compounds 3, 10, and 12 displayed the best interaction with 6LZG as compared to FDA-approved antiviral drugs Remdesivir and Baricitinib, while compounds 1, 10, and 8 exhibited strong linking with 6 M3 M and also better than Remdesivir and Baricitinib. Additionally, compounds 3, 1, and 6 showed promising interactions with 6LU7 but only compound 3 performed better than Baricitinib. An ADME (Absorption, Distribution, Metabolism, and Excretion) study provided insights into the pharmacokinetics and drug-likeness of these compounds, with all ligands demonstrating good physicochemical characteristics, lipophilicity, water solubility, pharmacokinetics, drug-likeness, and medicinal chemistry attributes. The results suggest that these selected thiazole derivatives hold promise as potential candidates for further drug development.

Exploration of Specific Fluoroquinolone Interaction with SARS-CoV-2 Main Protease (Mpro) to Battle COVID-19: DFT, Molecular Docking, ADME and Cardiotoxicity Studies.

Herein, the pharmacokinetic profiles, binding interactions, and molecular properties of fluoroquinolone derivatives as prospective antiviral drugs are examined using a combination of docking, ADME, and DFT simulations. The effectiveness of the ligands is compared with the clinically tested and FDA-authorized medicine remdesivir. The findings demonstrated encouraging binding energies, indicating possible inhibitory effectiveness against SARS-CoV-2 Mpro. The fluoroquinolone derivatives also exhibit promising ADME characteristics, although compounds 5, 6, 9, 12-20 possess poor values, suggesting that oral administration may be possible. The potential of the selected compounds as SARS-CoV-2 Mpro inhibitors is thoroughly understood because of the integrated analysis of DFT, with compound 11 demonstrating the highest energy gap of 0.2604 eV of, docking with viral targets with docking scores of -7.9 to -5.9 kcal/mol, with compound 18 demonstrating the highest docking score, which is at the 13th position in energy difference in the DFT data. Their favorable electrical properties, robust binding interactions with viral targets, and attractive pharmacokinetic profiles boost their potential as prospective study subjects. These substances have the potential to be transformed into cutting-edge antiviral therapies that specifically target SARS-CoV-2 Mpro and related coronaviruses.

HLA-B27, axial spondyloarthritis and survival.

INTRODUCTION: Ankylosing spondylitis (AS), and carriage of HLA-B27 gene in otherwise healthy individuals, are reportedly associated with increased mortality. We evaluated this hypothesis, using data from both a 35-year AS follow-up study and UK Biobank data. METHODS: In 1985, 363 members of the Swiss AS Patient Society and 806 relatives were screened clinically and then radiographically for AS/axial spondyloarthritis (axSpA). Life expectancy was analysed in 377 axSpA patients having available pelvic radiographs and HLA-B27 status, comparing with matched Swiss population data. Survival in relation to HLA-B27 status in the general population was studied in UK Biobank European-ancestry participants (n=407 480, n=30 419 deaths). RESULTS: AS patients have increased standardised mortality rate (SMR) compared with the general population (1.37, 95% CI 1.11 to 1.62). This increase was significant for HLA-B27-positive AS (SMR 1.38, 95% CI 1.11 to 1.65). Shortened life expectancy was observed among both HLA-B27-positive AS women (SMR 1.77, 95% CI 1.09 to 2.70) and men (SMR 1.31, 95% CI 1.02 to 1.59). Patients with non-radiographic axSpA (nr-axSpA) had significantly lower SMR: 0.44 (95% CI 0.23 to 0.77), compared with the general population. In the UK Biobank European-ancestry population cohort, HLA-B27 carriage was not significantly associated with any change in mortality (HR 1, 95% CI 0.97 to 1.1, p=0.349, adjusted by sex), in either males (HR 1, 95% CI 0.98 to 1.1, p=0.281) or females (HR 0.96, 95% CI 0.9 to 1, p=0.232), and no increase in vascular disease mortality was observed. DISCUSSION: AS patients, but not nr-axSpA patients, have a significantly shortened life expectancy. Increased mortality is particularly significant among women with HLA-B27-positive AS. HLA-B27 carriage in the European-ancestry general population does not influence survival, or the risk of death due to vascular disease.

Axial Spondyloarthritis and Diagnostic Challenges: Over-diagnosis, Misdiagnosis, and Under-diagnosis.

PURPOSE OF REVIEW: This article aims to review the challenges in axial spondyloarthritis diagnosis and identify the possible contributing factors. RECENT FINDINGS: The inability to reach an accurate diagnosis in a timely fashion can lead to treatment delays and worse disease outcomes. The lack of validated diagnostic criteria and the misuse of the currently available classification criteria could be contributing. There is also significant inter-reader variability in interpreting images, and the radiologic definitions of axial spondyloarthritis continue to be re-defined to improve their positive predictive value. The role of inflammatory back pain features, serologic biomarkers, genetics, and their diagnostic contribution to axial spondyloarthritis continues to be investigated. There is still a significant amount of delay in the diagnosis of axial spondyloarthritis. Appreciating the factors that contribute to this delay is of utmost importance to close the gap. It is similarly important to recognize other conditions that may present with symptoms that mimic axial spondyloarthritis so that misdiagnosis and wrong treatment can be avoided.

Design, Synthesis, Characterization and Computational Studies of Mannich Bases Oxadiazole Derivatives as New Class of Jack Bean Urease Inhibitors.

Mannich bases consisting of 1,3,4-oxadiazole-2-thione (3 a-3 l) bearing various substituents were synthesized and found potent jack bean urease inhibitors. The prepared compounds showed significantly good inhibitory activities with IC50 values from 9.45±0.05 to 267.42±0.23 µM. The compound 3 k containing 4-chlorophenyl (-R) and 4-hydroxyphenyl (-R') was most active with IC50 9.45±0.05 µM followed by 3 e (IC50 22.52±0.15 µM) in which -R was phenyl and -R' was isopropyl group. However, when both -R and -R' were either 4-chlorophenyl groups (3 l) or only -R' was 4-nitrophenyl (3 i), both compounds were found inactive. The detailed binding affinities of the produced compounds with protein were explored through molecular docking and data-supported in-vitro enzyme inhibition profiles. Drug likeness was confirmed by in silico ADME investigations and molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps were got from DFT calculations. ESP maps exposed that there are two potential binding sites with the most positive and most negative parts.

Investigations of Electronic, Structural, and In Silico Anticancer Potential of Persuasive Phytoestrogenic Isoflavene-Based Mannich Bases.

Isoflavenes have received the greatest research attention among the many groups of phytoestrogens. In this study, various isoflavene-based Mannich bases were selected for their theoretical studies. The purpose of this research was to discover the binding potential of all the designated Mannich bases acting as inhibitors against cancerous proteins EGFR, cMet, hTrkA, and HER2 (PDB codes: 5GTY, 3RHK, 6PL2, and 7JXH, respectively). For their virtual screening, DFT calculations and molecular docking studies were undertaken using in silico software. Docking studies predicted that ligands 5 and 15 exhibited the highest docking score by forming hydrogen bonds within the active pocket of protein 6PL2, ligands 1 and 15 both with protein 3RHK, and 7JXH, 12, and 17 with protein 5GTY. Rendering to the trends in polarizability and dipole moment, the energy gap values (0.2175 eV, 0.2106 eV) for the firm conformers of Mannich bases (1 and 4) replicate the increase in bioactivity and chemical reactivity. The energy gap values (0.2214 eV and 0.2172 eV) of benzoxazine-substituted isoflavene-based Mannich bases (9 and 10) reflect the increase in chemical potential due to the most stable conformational arrangements. The energy gap values (0.2188 eV and 0.2181 eV) of isoflavenes with tertiary amine-based Mannich bases (14 and 17) reflect the increase in chemical reactivity and bioactivity due to the most stable conformational arrangements. ADME was also employed to explore the pharmacokinetic properties of targeted moieties. This study revealed that these ligands have a strong potential to be used as drugs for cancer treatment.

Factors predicting axial spondyloarthritis among first-degree relatives of probands with ankylosing spondylitis: a family study spanning 35 years.

OBJECTIVE: Factors predicting axial spondyloarthritis (axSpA) among first-degree relatives (FDRs) of ankylosing spondylitis (AS) patients need to be defined. We investigated the predictive value of the probands' HLA-B27 and radiographic sacroiliitis status on disease occurrence among their FDR. We also assessed the predictive value of features of the clinical history, including chronic inflammatory back pain (CIBP) and acute anterior uveitis (AAU), among the FDR and how they can be used to improve classification and diagnosis of axSpA. METHODS: In 1985, we studied 363 AS probands and 806 FDR who underwent rheumatologic examination, completed questionnaires, provided blood samples for HLA-typing and underwent radiography of sacroiliac joints. At follow-up in 2018-2019, 125 patients and 360 FDR were available for study, and completed a postal questionnaire about axSpA features. FDRs were asked to report whether after 1985 they had been diagnosed by Swiss rheumatologists as having axSpA. RESULTS: Among HLA-B27(+) FDR, axSpA occurred in 25.4%-26.3%, independent of the radiographic sacroiliitis status of the proband. AAU occurred in 13/34 (38.2%) FDR with axSpA vs 29/251 (11.6%) FDR without axSpA (p=0.00004, OR=4.74 95% CI 2.15 to 10.47). The presence of CIBP at baseline did not predict later occurrence of axSpA but combining CIBP and pain/discomfort at the thoracic spine and at anterior (ventral) chest wall ever, assessed at follow-up in 2018-2019, provided 83.1% sensitivity and 87.2% specificity for current axSpA. CONCLUSION: Occurrence of AAU among FDR of axSpA probands should prompt screening for axSpA. Moreover, co-occurrence of CIBP and pain/discomfort in the thoracic spine and at anterior chest wall as a three-question tool may further enhance clinical suspicion of axSpA among these FDR.

Development of an environmental contextual factor item set relevant to global functioning and health in patients with axial spondyloarthritis.

OBJECTIVE: To describe the development of an Environmental contextual factors (EF) Item Set (EFIS) accompanying the disease specific Assessment of SpondyloArthritis international Society Health Index (ASAS HI). METHOD: First, a candidate item pool was developed by linking items from existing questionnaires to 13 EF previously selected for the International Classification of Functioning, Disability and Health (ICF) /ASAS Core Set. Second, using data from two international surveys, which contained the EF item pool as well as the items from the ASAS HI, the number of EF items was reduced based on the correlation between the item and the ASAS HI sum score combined with expert opinion. Third, the final English EFIS was translated into 15 languages and cross-culturally validated. RESULTS: The initial item pool contained 53 EF addressing four ICF EF chapters: products and technology (e1), support and relationship (e3), attitudes (e4) and health services (e5). Based on 1754 responses of axial spondyloarthritis patients in an international survey, 44 of 53 initial items were removed based on low correlations to the ASAS HI or redundancy combined with expert opinion. Nine items of the initial item pool (range correlation 0.21-0.49) form the final EFIS. The EFIS was translated into 15 languages and field tested in 24 countries. CONCLUSIONS: An EFIS is available complementing the ASAS HI and helps to interpret the ASAS HI results by gaining an understanding of the interaction between a health condition and contextual factors. The EFIS emphasizes the importance of support and relationships, as well as attitudes of the patient and health services in relation to self-reported health.

Synthesis, in Vitro Cholinesterase Inhibition, Molecular Docking, DFT, and ADME Studies of Novel 1,3,4-Oxadiazole-2-Thiol Derivatives.

A series of 1,3,4-oxadiazole-2-thiol derivatives bearing various alkyl or aryl moieties were designed, synthesized, and characterized using modern spectroscopic methods to yield 17 compounds (6a-6q) that were screened for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes in the search for 'lead' compounds for Alzheimer's disease treatment (AD). The compounds 6q, 6p, 6k, 6o, and 6l showed inhibitory capability against AChE and BChE, with IC50 values ranging from 11.73±0.49 to 27.36±0.29 µM for AChE and 21.83±0.39 to 39.43±0.44 µM for BChE, inhibiting both enzymes within a limited range. The SAR ascertained that the substitution of the aromatic moiety had a profound effect on the AChE and BChE inhibitory potential as compared to the aliphatic substitutions which were supported by the molecular docking studies. The drug-likeness of the most synthesized compounds was confirmed by in silico ADME investigations. These results were additionally supplemented by the molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps got from DFT calculations. ESP maps expose that on all structures, there are two potential binding sites conquered by the most positive and most negative districts.

Synthesis and Micromechanistic Studies of Sensitized Bentonite for Methyl Orange and Rhodamine-B Adsorption from Wastewater: Experimental and DFT-Based Analysis.

This work reports the formation of a novel adsorbent, prepared by activating bentonite with cinnamic acid, which is highly efficient to remove dyes from wastewater. The adsorption efficiency of the cinnamic acid activated bentonite was compared with unmodified bentonite by removing methyl orange and rhodamine-B from polluted water. The characterization was performed through X-ray diffraction (XRD) Fourier transform infrared (FTIR) and scanning electron microscopy (SEM). The results indicated that acidic pH and low temperature were more suitable for the selected dyes adsorption. The analysis of the data was done by the Langmuir and Freundlich isotherms; the Freundlich isotherm showed more suitability for the equilibrium data. The data were further analyzed by pseudo-first and pseudo-second-order models to study adsorption kinetics. The results showed that methyl orange and rhodamine-B adsorption obeyed pseudo-order kinetics. The results obtained from this research suggested that acid activation of bentonite with cinnamic acid increased the surface area of the clay and hence enhanced its adsorption efficiency. The maximum adsorption efficiency for the removal of methyl orange and rhodamine-B was up to 99.3 mg g-1 and 44.7 mg g-1, respectively, at 25 °C. This research provides an economical modification technique of bentonite, which makes it cost-effective and a good adsorbent for wastewater treatment.

Facile Synthesis of ZIF-67 for the Adsorption of Methyl Green from Wastewater: Integrating Molecular Models and Experimental Evidence to Comprehend the Removal Mechanism.

Organic dyes with enduring colors which are malodorous are a significant source of environmental deterioration due to their virulent effects on aquatic life and lethal carcinogenic effects on living organisms. In this study, the adsorption of methyl green (MG), a cationic dye, was achieved by using ZIF-67, which has been deemed an effective adsorbent for the removal of contaminants from wastewater. The characterization of ZIF-67 was done by FTIR, XRD, and SEM analysis. The adsorption mechanism and characteristics were investigated with the help of control batch experiments and theoretical studies. The systematical kinetic studies and isotherms were sanctioned with a pseudo-second-order model and a Langmuir model (R2 = 0.9951), confirming the chemisorption and monolayer interaction process, respectively. The maximum removal capacities of ZIF-67 for MG was 96% at pH = 11 and T = 25 °C. DFT calculations were done to predict the active sites in MG by molecular electrostatic potential (MEP). Furthermore, both Molecular dynamics and Monte Carlo simulations were also used to study the adsorption mechanism.

Worldwide Differences in Clinical Phenotype of Axial Spondyloarthritis.

PURPOSE OF REVIEW: This review aims to describe the variations in the clinical presentation of axial spondyloarthritis (axSpA) across the globe. RECENT FINDINGS: We searched the PubMed database and screened more than 1360 articles; 60 of them were selected based on relevance to the topic being discussed and the goals of the review. Most of the clinical manifestations, including IBP, peripheral arthritis, and extra-articular involvement are seen in different regions of the world, but with appreciable clinical heterogeneity, possibly related to a smaller number of patients from some countries, and global variation in the prevalence of HLA-B27. For example, HLA-B27-positive patients have an earlier age of onset, higher prevalence of acute anterior uveitis, and greater familial occurrence. Peripheral arthritis and enthesitis are most commonly seen among axSpA patients from Latin America and Asia, whereas IBD appears to be slightly more common among Middle Eastern and North African patients. The main weakness encountered while reviewing these data is that some studies were small, and others were cross-sectional and retrospective; hence the inferences may have a selection bias. AxSpA is a very heterogenous disease with varied presentation across the globe, in part related to HLA-B27 positivity. It is imperative to further investigate the key regional differences as they impact timely disease recognition and initiation of early treatment. Therefore, there is a need for a large worldwide systematic study to capture the clinical picture of AxSpA in a more uniform manner.

Diffuse Idiopathic Skeletal Hyperostosis (DISH) and a Possible Inflammatory Component.

PURPOSE OF REVIEW: Diffuse Idiopathic Skeletal Hyperostosis (DISH) is considered a metabolic condition, characterized by new bone formation affecting mainly at entheseal sites. Enthesitis and enthesopathies occur not only in the axial skeleton but also at some peripheral sites, and they resemble to some extent the enthesitis that is a cardinal feature in spondyloarthritis (SpA), which is an inflammatory disease. RECENT FINDINGS: We review the possible non-metabolic mechanism such as inflammation that may also be involved at some stage and help promote new bone formation in DISH. We discuss supporting pathogenic mechanisms for a local inflammation at sites typically affected by this disease, and that is also supported by imaging studies that report some similarities between DISH and SpA. Local inflammation, either primary or secondary to metabolic derangements, may contribute to new bone formation in DISH. This new hypothesis is expected to stimulate further research in both the metabolic and inflammatory pathways in order to better understand the mechanisms that lead to new bone formation. This may lead to development of measures that will help in earlier detection and effective management before damage occurs.

Review on the hazardous applications and photodegradation mechanisms of chlorophenols over different photocatalysts.

Chlorophenols are very important environmental pollutants, which have created huge problems for both aquatic and terrestrial lives. Therefore, their removal needs urgent, effective, and advanced technologies to safeguard our environment for future generation. This review encompasses a comprehensive study of the applications of chlorophenols, their hazardous effects and photocatalytic degradation under light illumination. The effect of various factors such as pH and presence of different anions on the photocatalytic oxidation of chlorophenols have been elaborated comprehensively. The production of different oxidizing agents taking part in the photodegradation of chlorophenols are given a bird eye view. The photocatalytic degradation mechanism of different chlorophenols over various photocatalyts has been discussed in more detail and elaborated that how different photocatalysts degrade the same chlorophenols with the aid of different oxidizing agents produced during photocatalysis. Finally, a future perspective has been given to deal with the effective removal of these hazardous pollutants from the environment.

The American College of Rheumatology Fibromyalgia Criteria Are Useful in the Evaluation of Fibromyalgia Symptoms in Patients With Ankylosing Spondylitis: A Cross-Sectional Study.

BACKGROUND: Fibromyalgia (FM) is common among patients with ankylosing spondylitis (AS), and its coexistence is believed to interfere with the measurement of patient-reported outcomes of disease activity and function in AS because of overlapping symptoms between the 2 diseases. This can confound clinical assessment and treatment decisions. AIMS: The aim of this study was to assess the relationship between the Fibromyalgia Symptom Scale (FSS) and its components, the Widespread Pain Index (WPI), and System Severity Scale with measures of disease activity, function, and patient-reported outcomes in AS. METHODS: We recruited 63 AS patients (aged ≥18 years) meeting the modified New York criteria, and Bath Ankylosing Spondylitis Disease Activity Index, Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein, Routine Assessment of Patient Index Data 3, and Bath Ankylosing Spondylitis Functional Index questionnaires were administered to them. The presence of FM was determined using validated 2010 American College of Rheumatology diagnostic criteria for FM. RESULTS: Twenty-eight of 63 patients (44.4%) with AS and FM had higher disease activity and greater impairment of functional ability compared with AS patients without FM. Using multiple linear regression estimates, there was no significant relationship of FSS scores with Bath Ankylosing Spondylitis Disease Activity Index (p = 0.36), Routine Assessment of Patient Index Data 3 (p = 0.50), Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (p = 0.24), Bath Ankylosing Spondylitis Functional Index (p = 0.42) scores, or erythrocyte sedimentation rate (p = 0.82) and C-reactive protein (p = 0.75). CONCLUSIONS: Despite a high prevalence of FM in our patients with the diagnosis of AS, there was no relationship between FSS and measures of disease activity or function in AS, suggesting that FSS and its components could be a useful tool to assess FM in AS patients. Also, FM impairs functional ability in patients with AS.

Organocatalyzed Solvent Free and Efficient Synthesis of 2,4,5-Trisubstituted Imidazoles as Potential Acetylcholinesterase Inhibitors for Alzheimer's Disease.

The catalytic potential of pyridine-2-carboxlic acid has been evaluated for efficient, green and solvent free synthesis of 2,4,5-trisubstituted imidazole derivatives 3a-3m. The compounds 3a-3m were synthesized by one pot condensation reaction of substituted aromatic aldehydes, benzil, and ammonium acetate in good to excellent yields (74-96 %). To explore the potential of these compounds against Alzheimer's disease, their inhibitory activities against acetylcholinesterase (AChE) were evaluated. In this series of compounds, compound 3m, bearing one ethoxy and a hydroxy group on the phenyl ring on 2,4,5-trisubstituted imidazoles, proved to be a potent AChE inhibitor (102.56±0.14). Structure-activity relationship (SAR) of these compounds was developed. Molecular dockings were carried out for the compounds 3m, 3e, 3k, 3c, 3a, 3d, 3j, and 3f in order to further investigate the binding mechanism. The inhibitor molecule was molecularly docked with acetylcholinesterase to further study its binding mechanism. The amino group of the compound 3m forms an H-bond with the oxygen atom of the residue (i. e., THR121) which has a bond length of 3.051 Å.

Association of rs10490924 in ARMS2/HTRA1 with age-related macular degeneration in the Pakistani population.

Age-related macular degeneration (AMD) is a disease of the elderly in which central vision is lost because of degenerative changes of the macula. The current study investigated the association of single-nucleotide polymorphisms (SNPs) with AMD in the Pakistani population. Four SNPs were analyzed in this study: rs1061170 in the CFH, rs429608 near CFB, rs2230199 in the C3, and rs10490924 in ARMS2/HTRA1. This case-control association study was conducted on 300 AMD patients (125 wet AMD and 175 dry AMD) and 200 unaffected age- and gender-matched control individuals. The association of the SNP genotypes and allele frequency distributions were compared between patients and healthy controls, keeping age, gender, and smoking status as covariates. A significant genotype and variant allele association was found of rs10490924 in ARMS2/HTRA1 with wet AMD, while the SNPs in CFH, CFB, and C3 were not associated with AMD in the current Pakistani cohort. The lack of association of CFH, CFB, and C3 may be attributed to limited sample size. This study demonstrates that genetic causative factors of AMD differ among populations and supports the need for genetic association studies among cohorts from various populations to increase our global understanding of the disease pathogenesis.

Sensitization of TiO2 nanosheets with Cu-biphenylamine framework to enhance photocatalytic degradation performance of toxic organic contaminants: synthesis, mechanism and kinetic studies.

TNS/Cu(X) composite materials were firstly synthesized via simple overnight stirring of TNS in the methanolic solution of Cu complexes. The developed TNS/Cu(X) composites had a well-designed nanostructure, in which the TNS and Cu complexes were closely bounded with each other. The biphenylamine complexes fixed on the TNS surface in form of nanocapsules, which were confirmed by TEM and SEM, thus improving the surface area and subsequently charge separation. Innovatively merged photocatalysts of Cu complexes with TNS were successfully verified for photocatalytic mineralization of colored and colorless organic contaminants under the visible light degradation. As compared to original TNS, TNS/Cu(BA) showed prominent improvement in the catalytic actions. Kinetics i.e. t 1/2 (half-life times period), K app, and R 2 (linear regression co-efficient) were also studied. The amended materials created charge separation, by means of electrons gathering at the higher CB, and holes gathering at the lower level valence band of the Cu complex, therefore improving mineralization efficiency of the electrons and holes. TNS/Cu(BA) degrade 99%-99.6% of methyl orange (MO) and rhodamine B (RhB) dyes at 120 min, and 160 min, respectively, and 68% of phenol and 53% of TCP were destroyed in 180 min. The resilient holes can directly destroy MO, RhB, phenol, and TCP.

A Systematic Review and Meta-analysis of Efficacy and Safety of Novel Interleukin Inhibitors in the Management of Psoriatic Arthritis.

OBJECTIVE: The aim of this study was to systemically review the efficacy and safety of inhibitors of interleukin 6 (IL-6): clazakizumab, IL-12/23: ustekinumab, and IL-17A: secukinumab, brodalumab, and ixekizumab in psoriatic arthritis (PsA). METHODS: The literature search was conducted using MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science. We included randomized controlled trials that assessed the efficacy of IL inhibitors and reported American College of Rheumatology 20 response at 24 weeks. Meta-analysis was done using random-effects model utilizing the DerSimonian and Laird method. Quality assessment was done using RobotReviewer Cochrane Risk-of-Bias Assessment Tool. Heterogeneity was assessed with Q statistic and quantified with I. Publication bias was assessed with a funnel plot. RESULTS: Eight studies including 2722 subjects demonstrate the efficacy of IL inhibitors clazakizumab, secukinumab, ixekizumab, brodalumab, and ustekinumab in the treatment of PsA. The American College of Rheumatology 20/50/70 risk ratios were 2.02 (95% confidence interval [CI], 1.65-2.47; P = 0.000), 2.95 (95% CI, 2.32-3.73; P = 0.00), and 5.14 (95% CI, 3.28-8.06; P = 0.00), respectively, in favor of treatment versus placebo. There was no evidence of significant heterogeneity between trials. Subgroup analysis showed efficacy in patients who were tumor necrosis factor naive, as well as tumor necrosis factor nonresponders or inadequate responders. The number of adverse events was higher in the treatment groups versus placebo, the majority were mild and did not require treatment adjustment (risk ratio, 1.17; 95% CI, 1.06-1.28; P = 0.001). There was no significant difference in drug withdrawals. CONCLUSIONS: Our meta-analysis shows that the inhibitors of IL-6 (clazakizumab), IL-12/23 (ustekinumab), and IL-17A (secukinumab, brodalumab, ixekizumab) are efficacious and generally well tolerated when used to treat patients with PsA.