Background: Airway inflammation is a feature of many respiratory diseases and there is a need for newer, more effective anti-inflammatory compounds. The aim of this study was to develop an ex vivo human lung explant model which can be used to help study the mechanisms underlying inflammatory responses and which can provide a tool to aid drug discovery for inflammatory respiratory diseases such as asthma and COPD. Method: Parenchymal lung tissue from 6 individual donors was dissected and cultured with two pro-inflammatory stimuli, lipopolysaccharide (LPS) (1 µg/ml) and interleukin-1 beta (IL-1β) (10 ng/ml) in the presence or absence of dexamethasone (1 µM). Inflammatory responses were assessed using Luminex analysis of tissue culture supernatants to measure levels of 21 chemokines, growth factors and cytokines. Results: A robust and reproducible inflammatory signal was detected across all donors for 12 of the analytes measured following LPS stimulation with a modest fold increase (<2-fold) in levels of CCL22, IL-4, and IL-2; increases of 2-4-fold in levels of CXCL8, VEGF and IL-6 and increases >4-fold in CCL3, CCL4, GM-CSF, IL-10, TNF-α and IL-1β. The inflammatory signal induced by IL-1β stimulation was less than that observed with LPS but resulted in elevated levels of 7 analytes (CXCL8, CCL3, CCL4, GM-CSF, IL-6, IL-10 and TNF-α). The inflammatory responses induced by both stimulations was supressed by dexamethasone for the majority of analytes. Conclusions: These data provide proof of concept that this ex vivo human lung explant model is responsive to inflammatory signals and could be used to investigate the anti-inflammatory effects of existing and novel compounds. In addition this model could be used to help define the mechanisms and pathways involved in development of inflammatory airway disease. Abbreviations: COPD: Chronic Obstructive Pulmonary Disease; ICS: inhaled corticosteroids; LPS: lipopolysaccharide; IL-1β: interleukin-1 beta; PSF: penicillin, streptomycin and fungizone
Background Low back pain (LBP) is a common musculoskeletal problem, associated with disability and high societal costs. The Oswestry Disability Index (ODI) is among the most commonly used patient reported outcome measures to measure disability due to LBP. Evidence supporting the reliability and validity of the Nepali Version of Oswestry Disability Index (NODI) exists, but its responsiveness is yet to be assessed. Objective We aimed to assess the responsiveness of NODI in participants with non-specific low back pain. Methods The study included 102 (Male 41, Female 61) participants with non-specific low back pain, attending the physiotherapy outpatient department of a tertiary care hospital and nearby community. The NODI was administered to the patients at baseline and again 2 weeks later along with a 7-item Nepali Version of Global Rating of Change (GROC-NP). Responsiveness of NODI was assessed by plotting Receivers Operating Characteristics (ROC) curve. Results The area under curve (AUC) of NODI was 0.88. The best cut-off point on the NODI for improvement on the GROC-NP or the minimal clinical important change (MIC) was 4.22 and ranged from 3.11 to 6.34. The sensitivity and specificity was 77.4% and 84.2% respectively. Conclusion NODI is a responsive scale which can discriminate between participants whose level of disability due to LBP is stable or improving. The result for minimal clinically important change, sensitivity and specificity are consistent with other cross culturally adopted versions.
Background Knee pain is one of the common causes of chronic pain mainly in the older adults.Chronic knee pain (CKP) is commonly due to arthritic changes (osteoarthritis). Chronic knee pain is a common and major health problem in ageing population. Knee pain is associated with high levels of disability. So early detection and treatment of pain related functional limitation is likely to have major influence on healthy ageing. The general objective of this study was to quantify the level of pain and physical function in patient with CKP. Methods Preliminary screening of population with chronic knee pain was taken and cross sectional descriptive study was done. Questionnaire with inclusion criteria was fulfilled with administration of Nepali version of Numerical Pain Rating Scale and Nepali version of Patient Specific Functional Scale on interview as well as self-report basis and the data was managed by SPSS version 23. Results 75.6% of female with chronic knee pain was found with the average pain level found to be 5 in N-NPRS scale.Among them 80.8% of chronic knee pain was due to knee osteoarthritis. Sitting function was found to be affected in 82.1% of population with mean Nepali version of Patient specific functional Scale score of 2. Similarly 80.8% reported going downstairs to be difficult due to knee pain with N-PSFS score of 2. Conclusion Pain and functional disability are the principle findings in patient with chronic knee pain for which they seek medical treatment .So the treatments should target on functional task with effective strategy. addressing disability. Focus on function is important for the development of optimal rehabilitation programs in patients with chronic knee pain.
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