PLOS ONE: [sortOrder=DATE_NEWEST_FIRST, sort=Date, newest first, filterJournals=PLoSONE, q=subject:"Rheumatology"]PLOShttps://journals.plos.org/plosone/webmaster@plos.orgaccelerating the publication of peer-reviewed sciencehttps://journals.plos.org/plosone/search/feed/atom?sortOrder=DATE_NEWEST_FIRST&unformattedQuery=subject:%22Rheumatology%22&sort=Date,+newest+first&filterJournals=PLoSONEAll PLOS articles are Open Access.https://journals.plos.org/plosone/resource/img/favicon.icohttps://journals.plos.org/plosone/resource/img/favicon.ico2024-03-29T14:47:51ZExamining the longitudinal associations between activity limitations, instrumental supports and social participation in osteoarthritis: A CLSA population-based studyAnthony V. PerruccioCalvin YipJ. Denise PowerMayilee CanizaresElizabeth M. Badley10.1371/journal.pone.02998942024-03-27T14:00:00Z2024-03-27T14:00:00Z<p>by Anthony V. Perruccio, Calvin Yip, J. Denise Power, Mayilee Canizares, Elizabeth M. Badley</p>
Objective <p>In osteoarthritis (OA) research, disability is largely studied within the context of activities of daily living. Broader consequences for social participation are often overlooked. In prior work, instrumental supports received and their perceived availability were shown to play a role in the maintenance of social participation. Two indicators of social participation were identified, diversity and intensity. The current study extends the findings from this prior cross-sectional work by examining these relationships longitudinally.</p> Methods <p>Data are from the baseline and 3-year follow-up questionnaires of the Canadian Longitudinal Study on Aging, a population-based study of people ages 45–85 years at baseline. The sample was restricted to those who at baseline reported a doctor diagnosis of OA (n = 4104). Using structural equation modeling, latent variables were derived at each time point for activity limitations, instrumental supports perceived and received, and social participation diversity and intensity. Longitudinal factorial invariance was assessed. Model covariates included age, sex, education, income, marital status, smoking status, obesity, and number of chronic conditions.</p> Results <p>For all latent variables, strong factorial longitudinal invariance was found. Activity limitations increased over time. Greater baseline social participation intensity was associated with increases in later intensity and diversity. Increasing activity limitations were associated with decreases in social participation and with increasing receipt of instrumental supports; they were not associated with changes in perceived availability of supports. However, increasing perceived availability was positively associated with social participation intensity.</p> Conclusions <p>With a goal of increasing social participation, findings suggest a focus on interventions to reduce activity limitations in OA is necessary. Findings additionally highlight an important role for perceived availability of instrumental supports in maintaining or improving social participation in OA, in addition to current social participation, particularly intensity, for future social participation status.</p>Machine learning-based prediction of rheumatoid arthritis with development of ACPA autoantibodies in the presence of non-HLA genes polymorphismsGrzegorz DudekSebastian SakowskiOlga BrzezińskaJoanna SarnikTomasz BudlewskiGrzegorz DraganMarta PoplawskaTomasz PoplawskiMichał BijakJoanna Makowska10.1371/journal.pone.03007172024-03-22T14:00:00Z2024-03-22T14:00:00Z<p>by Grzegorz Dudek, Sebastian Sakowski, Olga Brzezińska, Joanna Sarnik, Tomasz Budlewski, Grzegorz Dragan, Marta Poplawska, Tomasz Poplawski, Michał Bijak, Joanna Makowska</p>
Machine learning (ML) algorithms can handle complex genomic data and identify predictive patterns that may not be apparent through traditional statistical methods. They become popular tools for medical applications including prediction, diagnosis or treatment of complex diseases like rheumatoid arthritis (RA). RA is an autoimmune disease in which genetic factors play a major role. Among the most important genetic factors predisposing to the development of this disease and serving as genetic markers are HLA-DRB and non-HLA genes single nucleotide polymorphisms (SNPs). Another marker of RA is the presence of anticitrullinated peptide antibodies (ACPA) which is correlated with severity of RA. We use genetic data of SNPs in four non-HLA genes (PTPN22, STAT4, TRAF1, CD40 and PADI4) to predict the occurrence of ACPA positive RA in the Polish population. This work is a comprehensive comparative analysis, wherein we assess and juxtapose various ML classifiers. Our evaluation encompasses a range of models, including logistic regression, <i>k</i>-nearest neighbors, naïve Bayes, decision tree, boosted trees, multilayer perceptron, and support vector machines. The top-performing models demonstrated closely matched levels of accuracy, each distinguished by its particular strengths. Among these, we highly recommend the use of a decision tree as the foremost choice, given its exceptional performance and interpretability. The sensitivity and specificity of the ML models is about 70% that are satisfying. In addition, we introduce a novel feature importance estimation method characterized by its transparent interpretability and global optimality. This method allows us to thoroughly explore all conceivable combinations of polymorphisms, enabling us to pinpoint those possessing the highest predictive power. Taken together, these findings suggest that non-HLA SNPs allow to determine the group of individuals more prone to develop RA rheumatoid arthritis and further implement more precise preventive approach.Biomarker combination predicting imminent relapse after discontinuation of biological drugs in patients with rheumatoid arthritis in remissionEiji SakashitaKatsuya NagataniHitoshi EndoSeiji Minota10.1371/journal.pone.02994502024-03-21T14:00:00Z2024-03-21T14:00:00Z<p>by Eiji Sakashita, Katsuya Nagatani, Hitoshi Endo, Seiji Minota</p>
Objectives <p>Compared to conventional disease-modifying antirheumatic drugs (DMARDs), biological DMARDs demonstrate superior efficacy but come with higher costs and increased infection risks. The ability to stop and resume biological DMARD treatment while maintaining remission would significantly alleviate these barriers and anxieties. The objective of this study was to identify biomarkers that can predict an imminent relapse, hopefully enabling the timely resumption of biological DMARDs before relapse occurs.</p> Methods <p>Forty patients with rheumatoid arthritis who had been in remission for more than 12 months were included in the study. The patients discontinued their biological DMARD treatment and were monitored monthly for the next 24 months. Out of the 40 patients, 14 (35%) remained in remission at the end of the 24-month period, while 26 (65%) experienced relapses at different time points. Among the relapse cases, 13 patients experienced early relapse within 6 months, and another 13 patients had late relapse between 6 months and 24 months. Seventy-three cytokines in the sera collected longitudinally from the 13 patients with late relapse were measured by multiplex immunoassay. Using cytokines at two time points, immediately after withdrawal and just before relapse, volcano plot and area under the receiver operating characteristic curves (AUC) were drawn to select cytokines that distinguished imminent relapse. Univariate and multivariate logistic regression analyses were used for the imminent relapse prediction model.</p> Results <p>IL-6, IL-29, MMP-3, and thymic stromal lymphopoietin (TSLP) were selected as potential biomarkers for imminent relapse prediction. All four cytokines were upregulated at imminent relapse time point. Univariate and multivariate logistic regression showed that a combination model with IL-6, MMP-3, and TSLP yielded an AUC of 0.828 as top predictors of imminent relapse.</p> Conclusions <p>This methodology allows for the prediction of imminent relapse while patients are in remission, potentially enabling the implementation of on- and off-treatments while maintaining remission. It also helps alleviate patient anxiety regarding the high cost and infection risks associated with biological DMARDs, which are the main obstacles to benefiting from their superb efficacy.</p>Alterations in articular cartilage frictional properties in the setting of acute gouty arthritisPai ZhengXueer ZhangChengcheng FengYuhong YuGuangwei CheZhihong CaoLi TianYong Huang10.1371/journal.pone.02987222024-03-21T14:00:00Z2024-03-21T14:00:00Z<p>by Pai Zheng, Xueer Zhang, Chengcheng Feng, Yuhong Yu, Guangwei Che, Zhihong Cao, Li Tian, Yong Huang</p>
The tribological behaviour of articular cartilage plays a key role in joint motion; however, there is a gap in research on the effect of hyperuricemic joint fluid on cartilage friction behaviour in acute gouty arthritis. In this study, we carried out a fixed-load scratch experiment to compare the friction and wear of articular cartilage under the lubrication of gouty arthritis arthritic fluid and normal human arthritic fluid, and the results showed that the cartilage friction coefficient of patients with acute gouty arthritis was significantly larger than that of normal human beings, and that the cartilage friction coefficient decreased with the elevation of normal load and sliding speed, and the change with the sliding speed varied more differently from that of normal human beings, and that the cartilage surface wear was more severe after prolonged friction. The wear and tear of the cartilage surface is more severe after prolonged friction. Patients with gouty arthritis should reduce the sudden speed changes such as fast running and variable speed running to maintain the stability of the cartilage surface friction coefficient.Web-based survey investigating cardiovascular complications in hypermobile Ehlers-Danlos syndrome after COVID-19 infection and vaccinationAnthony L. GuerrerioAllyson MatejaGretchen MacCarrickJonathan FintziErica BrittainPamela A. Frischmeyer-GuerrerioHarry C. Dietz10.1371/journal.pone.02982722024-03-21T14:00:00Z2024-03-21T14:00:00Z<p>by Anthony L. Guerrerio, Allyson Mateja, Gretchen MacCarrick, Jonathan Fintzi, Erica Brittain, Pamela A. Frischmeyer-Guerrerio, Harry C. Dietz</p>
Background <p>Hypermobile Ehlers-Danlos syndrome is a heritable connective tissue disorder associated with generalized joint hypermobility but also other multisystem comorbidities, many of which may be exacerbated during a viral illness or after a vaccination. We sought to determine whether individuals with hypermobile Ehlers Danlos syndrome report an increase in adverse events, including cardiovascular events, after COVID-19 illness or vaccination.</p> Methods <p>A cross-sectional web-based survey was made available from November 22, 2021, through March 15, 2022. 368 respondents primarily from the United States self-reported data including diagnosis. We used a Cox proportional hazards model with time varying indicators for COVID-19 illness or vaccination in the previous 30 days.</p> Results <p>We found a significantly increased rate of new abnormal heart rhythms reported in the 30 days following COVID-19 illness. No additional cardiovascular events were reported after COVID-19 illness. 2.5% of respondents with COVID-19 illness were hospitalized. We did not find a statistically significant increased rate of cardiovascular events in the 30 days following any COVID-19 vaccination dose. Post COVID-19 vaccination, 87.2% of hypermobile Ehlers-Danlos syndrome respondents endorsed an expected adverse event (EAE), and 3.1% reported an emergency department visit/hospitalization, of those who received at least one vaccine dose. Events possibly reflecting exacerbation of orthostasis/dysautonomia were common.</p> Conclusion <p>Respondents did not report an increased rate of any cardiovascular events in the 30 days following COVID-19 vaccination; however, those with hypermobile Ehlers-Danlos syndrome experienced a high rate of expected adverse events after vaccination consistent with a high baseline prevalence of similar symptoms. No cardiovascular events other than new abnormal heart rhythms were reported at any point after a COVID-19 illness.</p>Cytokine and T cell responses in post-chikungunya viral arthritis: A cross-sectional studyAileen Y. ChangSarah R. TritschCarlos Andres Herrera GomezLiliana EncinalesAndres Cadena BonfantiWendy RosalesEvelyn Mendoza-TorresSamuel SimmensRichard L. AmdurChristopher N. MoresPaige FierbaughCarlos Alberto Perez HernandezGeraldine AvendañoPaula Bruges SilveraYerlenis Galvis CrespoAlberto David Cabana JimenezJennifer Carolina Martinez ZapataDennys JimenezEstefanie Osorio-LlanesJairo Castellar-LopezKarol SuchowieckiKaren MartinsMelissa GregoryIvan ZuluagaAbigale ProctorAlfonso Sucerquia HernándezLeandro Sierra-CarreroMaria Villanueva ColpasJuan Carlos Perez HernandezAndres Alberto Figueroa QuastJoaquin Andres Calderon De BarrosJosé Forero MejíaJohan Penagos RuizDavid BoyleGary S. FiresteinGary L. Simon10.1371/journal.pone.02995212024-03-20T14:00:00Z2024-03-20T14:00:00Z<p>by Aileen Y. Chang, Sarah R. Tritsch, Carlos Andres Herrera Gomez, Liliana Encinales, Andres Cadena Bonfanti, Wendy Rosales, Evelyn Mendoza-Torres, Samuel Simmens, Richard L. Amdur, Christopher N. Mores, Paige Fierbaugh, Carlos Alberto Perez Hernandez, Geraldine Avendaño, Paula Bruges Silvera, Yerlenis Galvis Crespo, Alberto David Cabana Jimenez, Jennifer Carolina Martinez Zapata, Dennys Jimenez, Estefanie Osorio-Llanes, Jairo Castellar-Lopez, Karol Suchowiecki, Karen Martins, Melissa Gregory, Ivan Zuluaga, Abigale Proctor, Alfonso Sucerquia Hernández, Leandro Sierra-Carrero, Maria Villanueva Colpas, Juan Carlos Perez Hernandez, Andres Alberto Figueroa Quast, Joaquin Andres Calderon De Barros, José Forero Mejía, Johan Penagos Ruiz, David Boyle, Gary S. Firestein, Gary L. Simon</p>
Objective <p>To define the relationship between chronic chikungunya post-viral arthritis disease severity, cytokine response and T cell subsets in order to identify potential targets for therapy.</p> Methods <p>Participants with chikungunya arthritis were recruited from Colombia from 2019–2021. Arthritis disease severity was quantified using the Disease Activity Score-28 and an Arthritis-Flare Questionnaire adapted for chikungunya arthritis. Plasma cytokine concentrations (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ and tumor necrosis factor (TNF)) were measured using a Meso Scale Diagnostics assay. Peripheral blood T cell subsets were measured using flow cytometry.</p> Results <p>Among participants with chikungunya arthritis (N = 158), IL-2 levels and frequency of regulatory T cells (Tregs) were low. Increased arthritis disease activity was associated with higher levels of inflammatory cytokines (IL-6, TNF and CRP) and immunoregulatory cytokine IL-10 (p<0.05). Increased arthritis flare activity was associated with higher Treg frequencies (p<0.05) without affecting T effector (Teff) frequencies, Treg/Teff ratios and Treg subsets. Finally, elevated levels of IL-2 were correlated with increased Treg frequency, percent Tregs out of CD4<sup>+</sup> T cells, and Treg subsets expressing immunosuppressive markers, while also correlating with an increased percent Teff out of live lymphocytes (p<0.05).</p> Conclusion <p>Chikungunya arthritis is characterized by increased inflammatory cytokines and deficient IL-2 and Treg responses. Greater levels of IL-2 were associated with improved Treg numbers and immunosuppressive markers. Future research may consider targeting these pathways for therapy.</p>Comparison across age groups of causes, circumstances, and consequences of falls among individuals living in Canada: A cross-sectional analysis of participants aged 45 to 85 years from the Canadian Longitudinal Study on AgingVanina P. M. Dal Bello-HaasMegan E. O’ConnellJake Ursenbach10.1371/journal.pone.03000262024-03-14T14:00:00Z2024-03-14T14:00:00Z<p>by Vanina P. M. Dal Bello-Haas, Megan E. O’Connell, Jake Ursenbach</p>
Falls are a leading cause of injury-related deaths and hospitalizations among Canadians. Falls risk has been reported to be increased in individuals who are older and with certain health conditions. It is unclear whether rurality is a risk factor for falls. This study aimed to investigate: 1) fall profiles by age group e.g., 45 to 54 years, 55 to 64 years, 65 to 74 years, 75 to 85 years; and 2) falls profiles of individuals, by age group, living in rural versus urban areas of Canada. Data (N = 51,338) from the Canadian Longitudinal Study on Aging was used to examine the relationship between falls and age, rurality, chronic conditions, need for medical attention, and fall characteristics (manner, location, injury). Self-reported falls within a twelve-month period occurred in only 4.8% (single fall) and 0.8% (multiple falls) of adults. Falls were not related to rural residence or age, but those with memory impairment, multiple sclerosis, as well as other chronic conditions such as mood disorder, anxiety disorder, and hyperthyroidism not often thought to be associated with falls, were also more likely to fall. Older individuals were more likely to fall indoors or fall while standing or walking. In contrast, middle-aged individuals were more likely to fall outdoors or while exercising. Type of injury was not associated with age, but older individuals were more likely to report hospitalization after a fall. This study shows that falls occur with a similar frequency in individuals regardless of age or urban/rural residence. Age was associated with fall location and activity. A more universally applicable multi-facted approach, rather than one solely based on older age considerations, to screening, primary prevention and management may reduce the personal, social, and economic burden of falls and fall-related injuries.Deep learning-based fully automated grading system for dry eye disease severitySeonghwan KimDaseul ParkYoumin ShinMee Kum KimHyun Sun JeonYoung-Gon KimChang Ho Yoon10.1371/journal.pone.02997762024-03-14T14:00:00Z2024-03-14T14:00:00Z<p>by Seonghwan Kim, Daseul Park, Youmin Shin, Mee Kum Kim, Hyun Sun Jeon, Young-Gon Kim, Chang Ho Yoon</p>
There is an increasing need for an objective grading system to evaluate the severity of dry eye disease (DED). In this study, a fully automated deep learning-based system for the assessment of DED severity was developed. Corneal fluorescein staining (CFS) images of DED patients from one hospital for system development (n = 1400) and from another hospital for external validation (n = 94) were collected. Three experts graded the CFS images using NEI scale, and the median value was used as ground truth. The system was developed in three steps: (1) corneal segmentation, (2) CFS candidate region classification, and (3) estimation of NEI grades by CFS density map generation. Also, two images taken on different days in 50 eyes (100 images) were compared to evaluate the probability of improvement or deterioration. The Dice coefficient of the segmentation model was 0.962. The correlation between the system and the ground truth data was 0.868 (p<0.001) and 0.863 (p<0.001) for the internal and external validation datasets, respectively. The agreement rate for improvement or deterioration was 88% (44/50). The fully automated deep learning-based grading system for DED severity can evaluate the CFS score with high accuracy and thus may have potential for clinical application.The association between a rotator cuff tendon tear and a tear of the long head of the biceps tendon: Chart review studyAbdulrahman AlraddadiBader AldebasiBander AlnufaieMohammed AlmuhannaMohammed AlkhalifahMotaz AleidanYousef MuradAwad M. AlmuklassAltayeb A. Ahmed10.1371/journal.pone.03002652024-03-11T14:00:00Z2024-03-11T14:00:00Z<p>by Abdulrahman Alraddadi, Bader Aldebasi, Bander Alnufaie, Mohammed Almuhanna, Mohammed Alkhalifah, Motaz Aleidan, Yousef Murad, Awad M. Almuklass, Altayeb A. Ahmed</p>
Rotator cuff (RC) and long head of the biceps tendon (LHBT) tears are common shoulder problems presented to the orthopedic clinic. The aim of this study was to assess the association between RC and LHBT tears among a Saudi population sample. A total of 243 patients who were diagnosed with shoulder pain due to RC or LHBT tear between 2016 and 2018 using a magnetic resonance imaging scan were included in this study. Females comprised 66% of the sample, and 59% (n = 143) of the shoulders were on the right side. The mean age of the patients was 58 ± 11 years, ranging from 23 to 88 years. A significant association was detected between the LHBT and RC tears (P < 0.001). Out of 26 cases showing RC and LHBT tears, 81% had a full thickness tear, whereas 19% had a partial tear. The LHBT tears were presented significantly in 48% of cases with at least two completely torn RC compared to 10% in cases with one completely torn RC (P < 0.001). The LHBT tear was significantly observed in shoulders with RC tears including the tendons of subscapularis, supraspinatus, and infraspinatus, but not the teres minor (P < 0.001). Both types of tears were presented significantly in senior patients aged more than 65 years compared to younger patients (P < 0.01). Thus, the LHBT should be assessed carefully in shoulders with more than one RC tear or in chronic cases.Modified Mesenchymal stem cell, platelet-rich plasma, and hyaluronic acid intervention in early stage osteoarthritis: A systematic review, meta-analysis, and meta-regression of arthroscopic-guided intra-articular approachesKevin Christian TjandraRobin NovriansyahI. Nyoman Sebastian SudiasaArdiyana ArNurul Azizah Dian RahmawatiIsmail Hadisoebroto Dilogo10.1371/journal.pone.02958762024-03-08T14:00:00Z2024-03-08T14:00:00Z<p>by Kevin Christian Tjandra, Robin Novriansyah, I. Nyoman Sebastian Sudiasa, Ardiyana Ar, Nurul Azizah Dian Rahmawati, Ismail Hadisoebroto Dilogo</p>
Background <p>Mesenchymal stem cells (MSCs) hold promise for osteoarthritis (OA) treatment, potentially enhanced by combining them with platelet-rich plasma (PRP) and hyaluronic acid (HA). This study aimed to assess the synergy of MSCs, PRP, and varying HA doses, and determine optimal MSC sources to treat early-stage OA in the perspective of Lysholm score, VAS Score, KSS score, and WOMAC score.</p> Method <p>Original articles from 2013 to 2023 were screened from four databases, focusing on clinical trials and randomized controlled trials. The Risk of Bias in Non-randomized Studies—of Interventions (ROB-2) tool evaluated bias, and a PICOS criteria table guided result construction. Revman 5.4 analyzed outcomes such as Lysholm score, VAS score, KSS, WOMAC score, cartilage volume, and defect size using MRI. This systematic review adhered to PRISMA guidelines.</p> Result <p>Nine studies met the final inclusion criteria. Meta-analysis revealed a significant improvement in Lysholm score (MD: 17.89; 95% CI: 16.01, 19.77; I2 = 0%, P = 0.56), a notable reduction in VAS score (MD: -2.62; 95% CI: -2.83, -2.41; I2 = 99%, P < 0.00001), elevated KSS (MD: 29.59; 95% CI: 27.66, 31.52; I2 = 95%, P < 0.0001), and reduced WOMAC score (MD: -12.38; 95% CI: -13.75, -11.01; I2 = 99%, P < 0.0001).</p> Conclusions <p>Arthroscopic guided high-dose subchondral application of primary cultured synovial MSCs in popliteal PRP media with HA effectively regenerates cartilage defects and improves clinical outcomes in early-stage osteoarthritis. Clarification of MSC sources and quantities enhances the understanding of this promising treatment modality.</p>Antidiabetic drug administration prevents bone mineral density loss: Evidence from a two-sample Mendelian randomization studyMingzhu ChenShuisen LinWanqiong ChenXiaoqiang Chen10.1371/journal.pone.03000092024-03-07T14:00:00Z2024-03-07T14:00:00Z<p>by Mingzhu Chen, Shuisen Lin, Wanqiong Chen, Xiaoqiang Chen</p>
The aim of this study was to investigate the effect of common antidiabetic drugs on BMD by two-sample Mendelian randomization (MR). The single nucleotide polymorphisms that were strongly associated with insulin, metformin, rosiglitazone and gliclazide were extracted as instrumental variables (IVs) for MR analysis. The inverse variance weighted (IVW) method was used as the primary MR method to assess the causal effect of antidiabetic drugs on BMD, and other MR methods, including Weighted median, MR Egger and Weighted mode, were used for complementary analysis. Reliability and stability were assessed by the leave-one-out test. In the present work, IVW estimation of the causal effect of insulin on heel BMD demonstrated that there was a null effect of insulin on heel BMD (β = 0.765; se = 0.971; <i>P</i> = 0.430), while metformin treatment had a positive effect on heel BMD (β = 1.414; se = 0.460; <i>P</i> = 2.118*10<sup>−3</sup>). The causal relationship between rosiglitazone and heel BMD analysed by IVW suggested that there was a null effect of rosiglitazone on heel BMD (β = -0.526; se = 1.744; <i>P</i> = 0.763), but the causal effect of gliclazide on heel BMD evaluated by IVW demonstrated that there was a positive effect of gliclazide on heel BMD (β = 2.671; se = 1.340; <i>P</i> = 0.046). In summary, the present work showed that metformin and gliclazide have a role in reducing BMD loss in patients with diabetes and are recommended for BMD loss prevention in diabetes.Developing a disease-specific patient reported outcome measure to enhance understanding of the lived experiences of ANCA associated vasculitis: A protocol paperLauren FloydAjay DhaygudeSandip MitraChristine Rowland10.1371/journal.pone.02987962024-03-07T14:00:00Z2024-03-07T14:00:00Z<p>by Lauren Floyd, Ajay Dhaygude, Sandip Mitra, Christine Rowland</p>
Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a chronic, relapsing-remitting condition associated with increased morbidity. Previous research has shown patients with AAV report high levels of fatigue, pain, depression and anxiety. Over recent years successful work has been carried out to improve clinical outcomes, resulting in reduced mortality and end stage kidney disease (ESKD). Despite this, little work has been done to better understand the role of the patient within this condition. The prevalence of AAV is increasing and to date, there is a shortage of specific tools that assess and measure key features relating to patient reported outcomes (PROs). This protocol details how we can better understand the lived experiences of those with AAV through the development of a disease specific, patient reported outcome measure (PROM), to be used in clinic practice. This will allow us to recognise and validate PROs and the impact the disease and its treatment has on patients’ health related quality of life (HRQoL). In addition, we aim to identify potential differences in PRO’s between demographics, organ involvement and treatment subgroups in AAV as well as outcomes relating to the patient experience. Patients from a single centre in the UK will be recruited to take part in the exploratory qualitative study which will include focus groups and semi-structured interviews. The inclusion criteria comprise anyone with a diagnosis of AAV and willing to participate, including those who have active or relapsing disease, those are economically active, unemployed, retired and patients receiving renal replacement therapy. The aim of the project is to identify key issues patients experience in relation to their disease and its management and how these can be better assessed in a new PROM developed for use in the clinic setting. This will enable better delivery of individualised care and inform shared decision making, while also serving as a platform for future research looking at PROs in other glomerulonephritides.Causal associations between rheumatoid arthritis, cataract and glaucoma in European and East Asian populations: A bidirectional two-sample mendelian randomization studyMenghao TengJiachen WangXiaochen SuYe TianJiqing WangYingang Zhang10.1371/journal.pone.02991922024-03-04T14:00:00Z2024-03-04T14:00:00Z<p>by Menghao Teng, Jiachen Wang, Xiaochen Su, Ye Tian, Jiqing Wang, Yingang Zhang</p>
Background <p>Previous studies have indicated a heightened susceptibility to cataract and glaucoma among rheumatoid arthritis (RA) patients, while it remains uncertain whether RA is causally associated with cataract and glaucoma. A two-sample mendelian randomization (MR) analysis was used to investigate the causal associations between RA, cataract and glaucoma in European and East Asian populations.</p> Methods <p>In the European population, genome-wide association study (GWAS) summary statistics for cataract (372,386 individuals) and glaucoma (377,277 individuals) were obtained from the FinnGen consortium (R9), while RA summary data were derived from a meta-analysis of GWAS encompassing 97173 samples. In the East Asian population, summary data for cataract (212453 individuals), glaucoma (212453 individuals), and RA (22515 individuals) were sourced from the IEU Open GWAS project. Inverse-variance weighted (IVW, random-effects) method served as the primary analysis, complemented by MR‒Egger regression, weighted median, weighted mode and simple mode methods. Additionally, various sensitivity tests, including Cochran’s Q test, MR‒Egger intercept, MR pleiotropy Residual Sum and Outlier test and leave-one-out test were performed to detect the heterogeneity, horizontal pleiotropy and stability of the analysis results.</p> Results <p>Following stringent screening, the number of selected instrumental variables ranged from 8 to 56. The IVW results revealed that RA had an increased risk of cataract (OR = 1.041, 95% CI = 1.019–1.064; P = 2.08×10<sup>−4</sup>) and glaucoma (OR = 1.029, 95% CI = 1.003–1.057; P = 2.94×10<sup>−2</sup>) in European populations, and RA displayed a positive association with cataract (OR = 1.021, 95% CI = 1.004–1.039; P = 1.64×10<sup>−2</sup>) in East Asian populations. Other methods also supported those results by IVW, and sensitivity tests showed that our analysis results were credible and stable.</p> Conclusions <p>This study revealed a positive causality between RA and the increased risk of cataract and glaucoma, which provides guidance for the early prevention of cataracts and glaucoma in patients with RA and furnishes evidence for the impact of RA-induced inflammation on ophthalmic diseases.</p>Chloroform associated with bone mineral density and bone mineral content in adults: A population-based cross-sectional researchLin LiXuekui LiuXia ZhangYan ZhangQing LiHoufa GengLi ShiBen WangQinqin QiuTianpei YuYiquan SangLyying WangWei XuJun Liang10.1371/journal.pone.02901322024-03-01T14:00:00Z2024-03-01T14:00:00Z<p>by Lin Li, Xuekui Liu, Xia Zhang, Yan Zhang, Qing Li, Houfa Geng, Li Shi, Ben Wang, Qinqin Qiu, Tianpei Yu, Yiquan Sang, Lyying Wang, Wei Xu, Jun Liang</p>
Background <p>Bone mineral density is an important indicator of osteoporosis, and its variation with volatile organic compounds exposure has rarely been studied. However, the relationship between chloroform (an essential volatile organic compounds component) and bone mineral density remains unclear. Consequently, we aimed to explore the relationship between chloroform alone and bone mineral density or bone mineral content.</p> Methods <p>Herein, 2,553 individuals aged 18 and above from the National Health and Nutrition Examination Surveys (NHANES) in 2009–2010, 2013–2014, and 2017–2020, were included. We employed two independent t-tests and multi-linear regression models to statistically assess the relationship between chloroform exposure and BMD/BMC in the spine and femoral area.</p> Results <p>A "V"-shaped correlation between chloroform exposure and bone mineral density or bone mineral content (BMD/BMC) was observed in the unadjusted model, particularly in the Ward’s triangle and femoral neck as a whole. A negative correlation was specifically observed for the Ward’s triangle BMD/BMC and L4 BMD/BMC. On the other hand, in the adjusted model, a dominantly negative correlation between the L4 BMC and chloroform exposure was observed over a range of exposure levels. The subgroup analysis revealed a negative correlation between chloroform concentrations and BMC in the femur and spine, especially in women and the 65–80 age population.</p> Conclusion <p>Our study revealed a "V" shaped correlation between chloroform and BMD/BMC of the femur and spine in U.S. adults. This finding highlights the fact that prolonged exposure to chloroform may cause the changes in BMD/BMC.</p>Protective effects of ectoine on articular chondrocytes and cartilage in rats for treating osteoarthritisPeng LiYong HuangLishuai MiaoZhiqi ZhuZhanjun Shi10.1371/journal.pone.02993512024-02-29T14:00:00Z2024-02-29T14:00:00Z<p>by Peng Li, Yong Huang, Lishuai Miao, Zhiqi Zhu, Zhanjun Shi</p>
Osteoarthritis (OA) is a chronic degenerative disease that primarily includes articular cartilage destruction and inflammatory reactions, and effective treatments for this disease are still lacking. The present study aimed to explore the protective effects of ectoine, a compatible solute found in nature, on chondrocytes in rats and its possible application in OA treatment. In the <i>in vitro</i> studies, the morphology of the chondrocytes after trypsin digestion for 2 min and the viability of the chondrocytes at 50°C were observed after ectoine treatment. The reactive oxygen species (ROS) levels in chondrocytes pretreated with ectoine and post-stimulated with H<sub>2</sub>O<sub>2</sub> were detected using an ROS assay. Chondrocytes were pretreated with ectoine before IL-1β stimulation. RT‒qPCR was used to measure the mRNA levels of cyclooxygenase-2 (COX-2), metallomatrix proteinase-3, -9 (MMP-3, -9), and collagen type II alpha 1 (Col2A1). In addition, immunofluorescence was used to assess the expression of type II collagen. The <i>in vivo</i> effect of ectoine was evaluated in a rat OA model induced by the modified Hulth method. The findings revealed that ectoine significantly increased the trypsin tolerance of chondrocytes, maintained the viability of the chondrocytes at 50°C, and improved their resistance to oxidation. Compared with IL-1β treatment alone, ectoine pretreatment significantly reduced COX-2, MMP-3, and MMP-9 expression and maintained type II collagen synthesis in chondrocytes. <i>In vivo</i>, the cartilage of ectoine-treated rats exhibited less degeneration and lower Osteoarthritis Research Society International (OARSI) scores. The results of this study suggest that ectoine exerts protective effects on chondrocytes and cartilage and can, therefore, be used as a potential therapeutic agent in the treatment of OA.