scholarly journals Modelling rheumatoid arthritis: A hybrid modelling framework to describe pannus formation in a small joint

2021 ◽  
Author(s):  
Fiona R Macfarlane ◽  
Mark AJ Chaplain ◽  
Raluca Eftimie

AbstractRheumatoid arthritis (RA) is a chronic inflammatory disorder that causes pain, swelling and stiffness in the joints, and negatively impacts the life of affected patients. The disease does not have a cure yet, as there are still many aspects of this complex disorder that are not fully understood. While mathematical models can shed light on some of these aspects, to date there are not many such models that can be used to better understand the disease. As a first step in the mechanistic understanding of RA, in this study we introduce a new hybrid mathematical modelling framework that describes pannus formation in a small proximal interphalangeal (PIP) joint. We perform numerical simulations with this new model, to investigate the impact of different levels of immune cells (macrophages and fibroblasts) on the degradation of bone and cartilage. Since many model parameters are unknown and cannot be estimated due to a lack of experiments, we also perform a sensitivity analysis of model outputs to various model parameters (single parameters or combinations of parameters). Finally, we connect our numerical results with current treatments for RA, by discussing our numerical simulations in the context of various drug therapies using, for example, methotrexate, TNF-inhibitors or tocilizumab, which can impact different model parameters.

2021 ◽  
Vol 1 ◽  
pp. 110-117
Author(s):  
Faiq Isho Gorial ◽  
Sattar Jabbar Naema ◽  
Hameed Oda Ali ◽  
Saad Abdulrahman Hussain

Background: Rheumatoid Arthritis (RA) is a chronic inflammatory disorder that impact daily life activities. The impact on work productivity is critical because of persistent work disability. Aim: To evaluate work productivity in RA patients compared to healthy controls, and to assess the impact of socio-demographic characteristics on work productivity. Methods: This was a case-control study conducted at the Rheumatology Unit of Baghdad Teaching Hospital, Medical City during the period from August 2020 to the end of March 2021. Seventy-two patients with RA were selected and compared with 72 healthy subjects as a control group. All patients were diagnosed according to ACR/EULAR 2010 RA classification criteria. The socio-demographic and clinical features, lifestyle practices, and disease activity of the patients and controls were all recorded during interviews. A standardized Arabic version of the Workplace Activity Limitation Scale (WALS) and the Job Limitations Questionnaire were used to assess the impact of RA on work productivity (WLQ-25). Results: The vast majority of patients were females (58.1%). Positive rheumatoid factor was reported in 94.4% of the patients. The patients showed a significantly lower WALS total score and higher WLQ-25 total score median (IQR) compared with controls. Conclusion: Active RA impairs the work productivity which was influenced by CDAI score and negatively associated with the use of DMARDs.


2020 ◽  
Author(s):  
Helen L Wright ◽  
Max Lyon ◽  
Elinor A Chapman ◽  
Robert J Moots ◽  
Steven W Edwards

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting synovial joints. Neutrophils are believed to play an important role in both the initiation and progression of RA, and large numbers of activated neutrophils are found within both synovial fluid (SF) and synovial tissue from RA joints. In this study we analysed paired blood and SF neutrophils from patients with severe, active RA (DAS28>5.1, n=3) using RNA-seq. 772 genes were significantly different between blood and SF neutrophils. IPA analysis predicted that SF neutrophils had increased expression of chemokines and ROS production, delayed apoptosis, and activation of signalling cascades regulating the production of NETs. This activated phenotype was confirmed experimentally by incubating healthy control neutrophils in cell-free RA SF, which was able to delay apoptosis and induce ROS production in both unprimed and TNFα primed neutrophils (p<0.05). RA SF significantly increased neutrophil migration through 3μM transwell chambers (p<0.05) and also increased production of NETs by healthy control neutrophils, including exposure of myeloperoxidase (MPO) and citrullinated histone-H3-positive DNA NETs. IPA analysis predicted NET production was mediated by signalling networks including AKT, RAF1, SRC and NF-κB. Our results expand the understanding of the molecular changes that take place in the neutrophil transcriptome during migration into inflamed joints in RA, and the altered phenotype in RA SF neutrophils. Specifically, RA SF neutrophils lose their migratory properties, residing within the joint to generate signals that promote joint damage, as well as inflammation via recruitment and activation of both innate and adaptive immune cells. We propose that this activated SF neutrophil phenotype contributes to the chronic inflammation and progressive damage to cartilage and bone observed in patients with RA.


2011 ◽  
Vol 26 (S2) ◽  
pp. 1745-1745
Author(s):  
N. Pilipenko ◽  
M. Karekla

Asthma is a chronic inflammatory disorder of the airways, ounknown etiology and growing prevalence (GINA, 2009). Appropriate asthma management can control the disorder and enable patients to enjoy a good quality of life (WHO, 2007).Yet, many asthma patients are unable to maintain asthma control (Rabe et al., 2003) for various reasons, including psychological ones (Feldman et al., 2005).This study examined the prevalence of psychomorbidity, and its interaction with asthma control difficulties and asthma-related quality of life in a sample of 200 asthma patients in Cyprus. Asthma diagnoses and severity were established by medical chart review.Psychomorbidity was evaluated using the Patient Health Questionnaire (Spitzer, 1999). Additionally, the impact of asthma-specific (e.g. asthma knowledge), health-specific (e.g. smoking history) and socio-demographic (e.g. perceived poverty) factors was examined as prior research literature suggests these may significantly impact asthma control and asthma-related quality of life.Currently, the present study is in its final stages of data collection (to conclude 2010). The results will offer valuable insights into the mechanisms and factors which affect asthma control, quality of life, and psychomorbidity. In doing so, the present study will contribute to the improved understanding of asthma patients’ experiences, essential to guide medical and psychological interventions.


Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3402
Author(s):  
Emilia Vassilopoulou ◽  
George N. Konstantinou ◽  
Anastasia Dimitriou ◽  
Yannis Manios ◽  
Lemonica Koumbi ◽  
...  

Asthma is a complex chronic inflammatory disorder. Diet’s impact on asthma symptoms is controversial. The objective of this pilot crossover, randomized, two-period study was to examine the effect of dietary histamine intake on asthma symptoms in twenty-one children with mild intermittent asthma. Children were randomly assigned to either a high- or low-histamine diet, based on the Mediterranean pattern, for 4 weeks. After a 2-week washout period, patients crossed to the alternative diet for 4 additional weeks. Asthma symptoms were assessed at baseline and after the completion of each diet period by a clinician. Daily symptoms and peak flow were recorded throughout the intervention. Adherence to the dietary intervention was assessed via analysis of four random 24-h recalls, for each intervention period. Eighteen children completed the study. Significantly higher mean air flow obstruction was recorded and a trend for prolonged and more severe symptoms was observed during the high-histamine period. Diet may have an active and direct impact on asthma symptoms. Food choice is affected and/or may affect symptoms in children with mild asthma. Diet intervention is promising yet challenging, for asthma control.


2016 ◽  
Vol 138 (5) ◽  
Author(s):  
Paul G. Arauz ◽  
Sue A. Sisto ◽  
Imin Kao

This article presented an assessment of quantitative measures of workspace (WS) attributes under simulated proximal interphalangeal (PIP) joint arthrodesis of the index finger. Seven healthy subjects were tested with the PIP joint unconstrained (UC) and constrained to selected angles using a motion analysis system. A model of the constrained finger was developed in order to address the impact of the inclusion of prescribed joint arthrodesis angles on WS attributes. Model parameters were obtained from system identification experiments involving flexion–extension (FE) movements of the UC and constrained finger. The data of experimental FE movements of the constrained finger were used to generate the two-dimensional (2D) WS boundaries and to validate the model. A weighted criterion was formulated to define an optimal constraint angle among several system parameters. Results indicated that a PIP joint immobilization angle of 40–50 deg of flexion maximized the 2D WS. The analysis of the aspect ratio of the 2D WS indicated that the WS was more evenly distributed as the imposed PIP joint constraint angle increased. With the imposed PIP joint constraint angles of 30 deg, 40 deg, 50 deg, and 60 deg of flexion, the normalized maximum distance of fingertip reach was reduced by approximately 3%, 4%, 7%, and 9%, respectively.


2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
E. A. Bakare ◽  
C. R. Nwozo

We formulated and analysed a mathematical model to explore the cointeraction between malaria and schistosomiasis. Qualitative and comprehensive mathematical techniques have been applied to analyse the model. The local stability of the disease-free and endemic equilibrium was analysed, respectively. However, the main theorem shows that if RMS<1, then the disease-free equilibrium is locally asymptotically stable and the phase will vanish out of the host and if RMS>1, a unique endemic equilibrium is also locally asymptotically stable and the disease persists at the endemic steady state. The impact of schistosomiasis and its treatment on malaria dynamics is also investigated. Numerical simulations using a set of reasonable parameter values show that the two epidemics coexist whenever their reproduction numbers exceed unity. Further, results of the full malaria-schistosomiasis model also suggest that an increase in the number of individuals infected with schistosomiasis in the presence of treatment results in a decrease in malaria cases. Sensitivity analysis was further carried out to investigate the influence of the model parameters on the transmission and spread of malaria-schistosomiasis coinfection. Numerical simulations were carried out to confirm our theoretical findings.


Author(s):  
Valerio Vallini ◽  
Luigi Venturini ◽  
Paolo Carnesecchi ◽  
Roberto Andreini ◽  
Simone Meini

Chronic limb-threatening ischemia (CLTI) represents an unfavorable evolution of peripheral artery disease, characterized by pain at rest, ulceration, and gangrene and also by an increased risk of cardiovascular events, amputations, and death. According to scientific literature, in almost one third of cases affected by CLTI, defined as no-option CLTI patients, revascularization strategies are not feasible. In the past decade, several studies investigated the role of therapeutic angiogenesis through cell autologous therapy, administered through intramuscular injections or multiple local intralesional and perilesional injections. In this article, we report the case of a necrotizing inflammatory reaction in a patient affected by CLTI and chronic leg wounds that occurred on the multiple injection sites after autologous peripheral blood-derived mononuclear cells (PB-TNCs) transplantation. Since the patient was affected by corticosteroid-induced skin atrophy and rheumatoid arthritis, we hypothesize that an increased skin fragility and a mechanism of immune-mediated pathergy could have been main factors leading to worsening of wounds. This case report strongly suggests the urgent need to better define the indications and contraindications of cell therapy, and further studies of adequate methodology are required to definitively assess the efficacy and safety of autologous cell therapy by local injections of PB-TNCs in patients with chronic inflammatory disorder, such as rheumatoid arthritis, especially in case of concomitant marked skin atrophy. Pending definitive evidence from literature, a strong caution is needed in patients affected by chronic systemic inflammatory diseases, since multiple injections, acting as mechanical stimulus and pathergy trigger, might exacerbate a severe and uncontrolled inflammatory response.


2013 ◽  
Vol 23 (2) ◽  
pp. 91-100 ◽  
Author(s):  
Aggie Stewart

Objectives: Rheumatoid arthritis (RA) is an autoimmune, chronic inflammatory disorder that causes pain, swelling, stiffness, loss of joint function, and reduced quality of life. Yoga therapy may help individuals with RA manage stress and increase well-being. This study focused on the identification of therapeutic objectives and a methodology to achieve symptom relief, regain function, and enhance quality of life for individuals with RA. Methods: Four women with RA participated in private yoga therapy sessions for 2.5 months. Assessment based, tailored home practices were developed and modified to address participant - identified goals. Results: Participants reported decreased pain, fatigue, swelling, and flares; increased energy; pain-free range of motion and strength around affected joints; and a heightened sense of well-being. Conclusions: Tailored yoga therapy that emphasizes stress reduction may be beneficial for individuals with RA.


Geosciences ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 64 ◽  
Author(s):  
Nejc Bezak ◽  
Jošt Sodnik ◽  
Matjaž Mikoš

Debris flows with different magnitudes can have a large impact on debris fan characteristics such as height or slope. Moreover, knowledge about the impact of random sequences of debris flows of different magnitudes on debris fan properties is sparse in the literature and can be improved using numerical simulations of debris fan formation. Therefore, in this paper we present the results of numerical simulations wherein we investigated the impact of a random sequence of debris flows on torrential fan formation, where the total volume of transported debris was kept constant, but different rheological properties were used. Overall, 62 debris flow events with different magnitudes from 100 m3 to 20,000 m3 were selected, and the total volume was approximately 225,000 m3. The sequence of these debris flows was randomly generated, and selected debris fan characteristics after the 62 events were compared. For modeling purposes, we applied the Rapid Mass Movement Simulations (RAMMS) software and its debris flow module (RAMMS-DF). The modeling was carried out using (a) real fan topography from an alpine environment (i.e., an actual debris fan in north-west (NW) Slovenia formed by the Suhelj torrent) and (b) an artificial surface with a constant slope. Several RAMMS model parameters were tested. The simulation results confirm that the random sequence of debris flow events has only some minor effects on the fan formation (e.g., slope, maximum height), even when changing debris flow rheological properties in a wide range. After the 62 events, independent of the selected sequence of debris flows, the final fan characteristics were not significantly different from each other. Mann–Whitney (MW) tests and t-tests were used for this purpose, and the selected significance level was 0.05. Moreover, this conclusion applies for artificial and real terrain and for a wide range of tested RAMMS model rheological parameters. Further testing of the RAMMS-DF model in real situations is proposed in order to better understand its applicability and limitations under real conditions for debris flow hazard assessment or the planning of mitigation measures.


Author(s):  
Isabel Maria Oliveira ◽  
Diogo Castro Fernandes ◽  
Ibrahim Fatih Cengiz ◽  
Rui Luís Reis ◽  
Joaquim Miguel Oliveira

AbstractRheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disorder that mostly affects the synovial joints and can promote both cartilage and bone tissue destruction. Several conservative treatments are available to relieve pain and control the inflammation; however, traditional drugs administration are not fully effective and present severe undesired side effects. Hydrogels are a very attractive platform as a drug delivery system to guarantee these handicaps are reduced, and the therapeutic effect from the drugs is maximized. Furthermore, hydrogels can mimic the physiological microenvironment and have the mechanical behavior needed for use as cartilage in vitro model. The testing of these advanced delivery systems is still bound to animal disease models that have shown low predictability. Alternatively, hydrogel-based human dynamic in vitro systems can be used to model diseases, bypassing some of the animal testing problems. RA dynamic disease models are still in an embryonary stage since advances regarding healthy and inflamed cartilage models are currently giving the first steps regarding complexity increase. Herein, recent studies using hydrogels in the treatment of RA, featuring different hydrogel formulations are discussed. Besides, their use as artificial extracellular matrices in dynamic in vitro articular cartilage is also reviewed.


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