Bruton's tyrosine kinase inhibition suppresses neutrophilic inflammation and restores histone deacetylase 2 expression in myeloid and structural cells in a mixed granulocytic mouse model of asthma.

Asthmatic inflammation is not a single homogenous inflammation but may be categorized into several phenotypes/endotypes. Severe asthma is characterized by mixed granulocytic inflammation in which there is increased presence of neutrophilic numbers and unresponsiveness to corticosteroids. Neutrophilic oxidative stress and histone deacetylase 2 (HDAC2) dysregulation in the pulmonary compartment are thought to lead to corticosteroid insensitivity in severe asthma with mixed granulocytic inflammation. Bruton's tyrosine kinase (BTK) is a no-receptor tyrosine kinase which is expressed in innate immune cells such as neutrophils and dendritic cells (DCs) where it is incriminated in balancing of inflammatory signaling. We hypothesized in this study that BTK inhibition strategy could be utilized to restore corticosteroid responsiveness in mixed granulocytic asthma. Therefore, combined therapy of BTK inhibitor (ibrutinib) and corticosteroid, dexamethasone was administered in cockroach allergen extract (CE)-induced mixed granulocyte airway inflammation model in mice. Our data show that CE-induced neutrophilic inflammation was concomitant with HDAC2 expression and upregulation of p-NFkB expression in airway epithelial cells (AECs), myeloid cells and pulmonary tissue. Further, there were increased expression/release of inflammatory and oxidative mediators such as MUC5AC, TNF-α, GM-CSF, MCP-1, iNOS, nitrotyrosine, MPO, lipid peroxides in AECs/myeloid cells/pulmonary tissue. Dexamethasone alone significantly attenuated eosinophilic inflammation and inflammatory cytokines but was not able to control oxidative inflammation. Ibrutinib alone markedly reduced neutrophilic infiltration and oxidative inflammation, and restored HDAC2 without having any significant effect on eosinophilic inflammation. These data suggest that BTK inhibition strategy may be used in conjunction with dexamethasone to treat both neutrophilic and eosinophilic inflammation, i.e. mixed granulocytic asthma.

The Diagnostic Value of Clinical Sacroiliac Joint Pain Provocation Tests for Detection of Sacroiliitis Identified by MRI in Sampled Iraqi Patients with Inflammatory Back Pain.

Background: Sacroiliitis has been considered as the keystone in the diagnosis of axial spondyloarthritis (SPA). The diagnosis can be challenging in early stages of sacroiliitis, as conventional radiographs may be normal. Pain provocative tests can be very helpful to give a clue whether sacroiliitis is present in suspected patient by reproducing the patient's pain. Objective: To assess the validity of clinical sacroiliac joint pain provocation tests for sacroiliitis in comparison with magnetic resonance imaging (MRI). Patients and methods: A total of 65 patients were selected from cohort of patients with persistent inflammatory low back pain during their attendance to the Rheumatology Consultant Clinic at Baghdad Teaching Hospital. Data were collected using questionnaire and interview. Socio-demographic characteristics, disease duration and clinical data were recorded for all patients. Data from four different clinical examination tests (Flexion Abduction and External Rotation [FABER], direct compression, distraction, and lateral compression) with subsequent MRI findings of sacroiliac joint for each patient were analysed. Positive MRI findings were further subdivided into active and chronic lesions according to the new ASAS (association of spondyloarthritis international society) criteria of positive imaging in spondyloarthropathy. Results: A total of 65 patients were included in this study, age range 18-39 years, 69.2% were men. The prevalence of sacroiliitis in the study was 67.7% (43.1% bone marrow oedema, 18.5% erosions, 15.4% sclerosis, 6.2 % for each of effusion; ankyloses and capsulitis). In the whole study group, the highest association with sacroiliitis was for FABER test with sensitivity of 75% while the most specific one was the lateral compression test (71.4%). In men, sacroiliitis was associated with sacroiliac joint (SIJ) clinical tests assessed in multi-test regimens; significant association was found by combining direct compression and FABER test with sensitivity of 51% and specificity of 28.5%. Conclusion: This study identified the reliability of a number of clinical examination tests of SIJ, which increase as they are used in multi-test regimen rather than each one alone, this had a significant association for men only.

2021 Asia-Pacific League of Associations for Rheumatology clinical practice guideline for treatment of gout.

BACKGROUND: Gout is the most prevalent inflammatory arthritis in the Asia-Pacific region and worldwide. This clinical practice guideline (CPG) aims to provide recommendations based on systematically obtained evidence and values and preferences tailored to the unique needs of patients with gout and hyperuricemia in Asia, Australasia, and the Middle East. The target users of these guidelines are general practitioners and specialists, including rheumatologists, in these regions. METHODS: Relevant clinical questions were formulated by the Steering Committee. Systematic reviews of evidence were done, and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation methodology. A multi-sectoral consensus panel formulated the final recommendations. RESULTS: The Asia-Pacific League of Associations for Rheumatology Task Force developed this CPG for treatment of gout with 3 overarching principles and 22 recommendation statements that covered the treatment of asymptomatic hyperuricemia (2 statements), treatment of acute gout (4 statements), prophylaxis against gout flare when initiating urate-lowering therapy (3 statements), urate-lowering therapy (3 statements), treatment of chronic tophaceous gout (2 statements), treatment of complicated gout and non-responders (2 statements), treatment of gout with moderate to severe renal impairment (1 statement), and non-pharmacologic interventions (5 statements). CONCLUSION: Recommendations for clinically relevant scenarios in the management of gout were formulated to guide physicians in administering individualized care.

Heat transfer enhancement of laminar nanofluids flow in a circular tube fitted with parabolic-cut twisted tape inserts.

Numerical investigation has been carried out on heat transfer and friction factor characteristics of copper-water nanofluid flow in a constant heat-fluxed tube with the existence of new configuration of vortex generator using Computational Fluid Dynamics (CFD) simulation. Two types of swirl flow generator: Classical twisted tape (CTT) and Parabolic-cut twisted tape (PCT) with a different twist ratio (y = 2.93, 3.91 and 4.89) and different cut depth (w = 0.5, 1.0 and 1.5 cm) with 2% and 4% volume concentration of CuO nanofluid were used for simulation. The effect of different parameters such as flow Reynolds number, twist ratio, cut depth and nanofluid were considered. The results show that the enhancement of heat transfer rate and the friction factor induced by the Classical (CTT) and Parabolic-cut (PCT) inserts increases with twist ratio and cut depth decreases. The results also revealed that the heat transfer enhancement increases with an increase in the volume fraction of the CuO nanoparticle. Furthermore, the twisted tape with twist ratio (y = 2.93) and cut depth w = 0.5 cm offered 10% enhancement of the average Nusselt number with significant increases in friction factor than those of Classical twisted tape.

Numerical investigation of heat transfer and friction factor characteristics in a circular tube fitted with V-cut twisted tape inserts.

Numerical investigation of the heat transfer and friction factor characteristics of a circular fitted with V-cut twisted tape (VCT) insert with twist ratio (y = 2.93) and different cut depths (w = 0.5, 1, and 1.5 cm) were studied for laminar flow using CFD package (FLUENT-6.3.26). The data obtained from plain tube were verified with the literature correlation to ensure the validation of simulation results. Classical twisted tape (CTT) with different twist ratios (y = 2.93, 3.91, 4.89) were also studied for comparison. The results show that the enhancement of heat transfer rate induced by the classical and V-cut twisted tape inserts increases with the Reynolds number and decreases with twist ratio. The results also revealed that the V-cut twisted tape with twist ratio y = 2.93 and cut depth w = 0.5 cm offered higher heat transfer rate with significant increases in friction factor than other tapes. In addition the results of V-cut twist tape compared with experimental and simulated data of right-left helical tape inserts (RLT), it is found that the V-cut twist tape offered better thermal contact between the surface and the fluid which ultimately leads to a high heat transfer coefficient. Consequently, 107% of maximum heat transfer was obtained by using this configuration.

Correlation of lung function with disease activity rheumatoid arthritis.

OBJECTIVES: To find a correlation between Lung function with the disease activity in Rheumatoid arthritis (RA). METHODS: The study was carried out on 40 (35 female and 5 male) patients with active RA who fulfilled the ARA 1987 reversed criteria for the classification of RA. Patients with signs and symptoms of respiratory disease or chest injury were excluded from this study. The patients were all examined clinically by weighted and selective index for active synovitis and assessed for functional status of the follwing; ESR, Hb % level, pulmonary function tests including FEV1, VC, FEV,/ FVC and DL(CO). Another group of 30 (27 female and 3 male) patients with active RA served as a control group. RESULTS: The results showed that Hb level ranged between (7-13.3 gm/dl), ESR ranged between 11-131 mm/hr and restrictive ventilatory defect was observed in 15 (37.5%) patients. Obstructive ventilator defect was presented in 10 (25%) patients. A decreased in DLCO was detected in 23 (51.5%) patients. There was a positive correlation between PETS with Hb%, ESR, Disease duration and activity of synovitis (P<0.005). CONCLUSION: Lung function can be used to stratify abnormalities in a clinically useful manner and can be used as an indicator of disease activity in RA.