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Objective: Quercetin is a flavonoid with anti-inflammatory properties and is used in a few rheumatic conditions. Herein, the authors review the rheumatological diseases in which quercetin has been investigated: rheumatoid arthritis, osteoarthritis, gout, and pre-hyperuricemia. Materials and Methods: A systematic search of articles published in PubMed/MEDLINE, Web of Sciences, LILACS, and Scielo from 1966 to August 2022 was done. No language restriction was used. The reference lists in the selected articles were analyzed to identify other publications. Results: There are only 6 articles published in this field, involving a total of 284 patients. Rheumatoid arthritis was the most studied disease (n=3 articles), and then osteoarthritis (n=2), gout (n=1), and pre-hyperuricemic subjects (n=1). Age varied from 19 to 62.5 years old; females predominated, ranging from 83% to 100% in most studies. However, all participants were male in the two articles in which gout and pre-hyperuricemia were evaluated. Disease duration varied from 5.0 to 10 years. Quercetin dosage ranged from 45 mg to 2000 mg/day. Regarding outcome, all studies except one showed a good result after quercetin treatment, with improved pain, morning stiffness, disease activity score-28 joints (DAS28), uric acid, inflammatory biomarkers, and other parameters in the studied diseases. Conclusions: This review shows that quercetin use in some rheumatic diseases has good effects, although new studies to confirm these findings are needed.

The identification of novel, yet easily measurable biomarkers of inflammation and oxidative stress might assist in the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a systematic review and meta-analysis of studies investigating the circulating concentrations of bilirubin, the end product of heme metabolism and a potent endogenous antioxidant with anti-inflammatory properties, in patients with RDs and healthy controls. The electronic databases PubMed, Scopus, and Web of Science were searched from inception to 31 December 2023 for relevant articles. We evaluated the risk of bias and the certainty of evidence using the Joanna Briggs Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation Working Group system, respectively. In 17 eligible studies, all with low risk of bias, compared to controls, patients with RDs had significantly lower concentrations of total bilirubin (standard mean difference, SMD=-0.68, 95% CI -0.91 to -0.44, p

Contraception is an important aspect of reproductive health in patients with rheumatic diseases. This is primarily due to the fact that in most immuneinflammatory rheumatic diseases (IRD) pregnancy must be planned. On one hand, the presence and activity of IRD can influence the course of the pregnancy, but on the other hand, pregnancy, which is accompanied by changes in general hormonal levels, is often a factor that alters the activity of IRD. Some patients take medication with potentially teratogenic effects. Planning a pregnancy during IRD can contribute to its optimal progression and minimize the risks of exacerbation of IRD. Given the wide range of barrier and hormonal contraceptives currently in use and the introduction of new drugs into clinical practice, data on the possibility of their use are of particular importance to rheumatologists in practical healthcare.

Abstract Background Opioids are not recommended for fibromyalgia. Objective To investigate the frequency of opioid use in a large cohort of fibromyalgia patients and to identify factors associated with opioid consumption. Methods A retrospective, observational study of a large fibromyalgia cohort in a tertiary care center. We assessed fibromyalgia severity, functional capacity, anxiety, depression, drugs consumption and the patient’s impression of change. We compared strong opioid consumers (SOC) and non-SOC. Inferential statistical and logistic regression analysis were used to identify factors associated with opioid consumption, and ANOVA for repeated measurements. Results We found a prevalence of 9.2% of SOC (100 patients) among 1087 patients in the cohort. During the last four years there was a significant increase on the incidence of SOC up to 12.8% (p = 0.004). There were no differences in demographic variables between SOC and non-SOC. Clinical variables were significantly more severe in SOC, and they consumed more non-opioid drugs (p

Abstract Background Patients with rheumatic diseases (RDs) have a lower desire to have children, fewer children, and a longer interval between their pregnancies, which can be due to the patient’s personal choice, the physician’s advice, changes in sexual activity, changes in fertility, and pregnancy failure. This study aimed to explore the understanding and experience of women with RDs regarding pregnancy intention. Method In Mashhad, Northeast Iran, between December 2022 and March 2023, this qualitative inquiry was carried out. Purposive sampling was used to select thirty women with RDs. Semi-structured interviews were used to collect the data. Graneheim and Lundman’s conventional content analysis method was used to analyze the data. The data organization was done using MAXQDA 12 software. Credibility, dependability, confirmability, and transferability have been considered as elements of trustworthiness. Results The participants’ data analysis revealed the following main theme: “duality of desire and fear in childbearing”. Five main categories were identified, including “Individual health concerns following pregnancy”, “motherhood and womanhood perceptions”, “concerns about child harm”, “contradictory beliefs and attitudes of significant family members and clinicians about pregnancy”, and “lack of social support for fertility”. Conclusion In order to improve the outcomes of pregnancy for women with RDs, the medical professionals who manage them must actively and frequently inquire about their intentions to childbearing and offer them individualized guidance on how to be in the best possible health at the time of conception. Rheumatologists, gynecologists, and reproductive health specialists can better address the sexual and reproductive health needs of this population by enhancing their collaboration in the care of women with RDs.

Abstract Background There is an increased risk of cardiovascular disease in people with many rheumatic diseases. The primary objective of this study was to evaluate cardiovascular disease hospitalizations in Alaska for people with and without a rheumatic disease diagnosis and assess disparities by race, with a focus on Alaska Native and American Indian people. Methods This study used the Alaska Health Facilities Data Reporting Program data on inpatient hospitalizations from 2015 to 2018. We identified people with a rheumatic disease diagnosis based on any hospitalization with a set of rheumatic disease diagnoses and compared them to people hospitalized but without a rheumatic disease diagnosis. We determined the odds of cardiovascular disease hospitalization by rheumatic disease diagnosis and assessed the influence of race and other factors, using univariate analyses and multivariable models. Results People with a rheumatic disease diagnosis other than osteoarthritis had higher odds of cardiovascular disease hospitalization. The odds ratio was highest in people with gout compared to other rheumatic diseases. In multivariable models, there was an interaction between race and rheumatic disease status. Specifically, having gout increased the odds of cardiovascular disease hospitalization for people of all races, while having a rheumatic disease other than gout or osteoarthritis increased the odds of cardiovascular disease hospitalization in Alaska Native/American Indian people but not in people of other races. Conclusions The association between rheumatic disease status and cardiovascular disease hospitalization in Alaska varied by type of rheumatic disease and race. This adds substantially to the literature on associations between rheumatic disease and cardiovascular disease in Indigenous North American populations.

Xue-Mei Liu,1,2,* Liu Yang,1,2,* Qi-Bin Yang1 1Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, 637000, People’s Republic of China; 2Department of Clinical Medicine, Graduate School of North Sichuan Medical College, Nanchong, Sichuan Province, 637000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qi-Bin Yang, Department of Rheumatology and Immunology, Affiliated Hospital, North Sichuan Medical College, 1 Maoyuannan Road, Nanchong, Sichuan Province, 637000, People’s Republic of China, Tel +86-817-259-8221, Email yangqb_001@163.comAbstract: Rheumatic disease is a disease which is not yet fully clarified to etiology and also involved in a local pathological injury or systemic disease. With the continuous improvement of clinical medical research in recent years, the development process of rheumatic diseases has been gradually elucidated; with the intensely study of epigenetics, it is realized that environmental changes can affect genetics, among which histone acetylation is one of the essential mechanisms in epigenetics. Histone deacetylases (HDACs) play an important role in regulating gene expression in various biological processes, including differentiation, development, stress response, and injury. HDACs are involved in a variety of physiological processes and are promising drug targets in various pathological conditions, such as cancer, cardiac and neurodegenerative diseases, inflammation, metabolic and immune disorders, and viral and parasitic infections. In this paper, we reviewed the roles of HDACs in rheumatic diseases in terms of their classification and function.Keywords: histone deacetylase, histone deacetylase inhibitor, rheumatic diseases

Abstract Autoimmune congenital heart block (ACHB) is a passively acquired immune-mediated disease characterized by the presence of maternal antibodies against components of the Ro/SSA and La/SSB ribonucleoprotein complex that mainly affects the cardiac conducting system. ACHB occurs in 2% of women with positive anti-Ro/SSA and anti-La/SSB antibodies and causes a high risk of intrauterine fetal death, neonatal mortality, and long-term sequelae. In this review, we first describe a case of ACHB to provide preliminary knowledge. Then, we discuss the possible pathogenic mechanisms of ACHB; summarize the pregnancy management of patients with positive anti-Ro/SSA and anti-La/SSB antibodies and/or rheumatic diseases, the prevention of ACHB, and the treatment of ACHB fetuses; and propose routine screening of these antibodies for the general population. Careful follow-up, which consists of monitoring the fetal heart rate, is feasible and reassuring for pregnant women with positive anti-Ro/SSA and/or anti-La/SSB antibodies to lower the risk of ACHB in fetuses. Moreover, maternal administration of hydroxychloroquine may be useful in preventing ACHB in pregnant women with anti-Ro/SSA and/or anti-La/SSB antibodies.

Abstract Introduction The purpose of this study was to investigate whether the inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine has a similar effectiveness and safety profile in patients with rheumatic and musculoskeletal diseases (RMDs) and healthy controls (HCs). Methods Between August 10, 2021 and September 30, 2021, 134 HCs and 269 patients with RMDs were recruited. All participants who tested negative for COVID-19 were vaccinated with SARS-CoV-2 inactivated vaccine. Next, 150 patients with RMDs and 30 HCs infected with the SARS-CoV-2 Omicron variant within the previous 12 weeks were recruited between February 20, 2023 and March 1, 2023. Serum samples were collected from each participant, and the serum immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody titers against SARS-CoV-2 were determined using a chemiluminescence assay. Results No statistically significant difference was found in the titer of anti-SARS-CoV-2 IgG and IgM antibodies, or in the incidence of vaccination-related adverse events between the RMD and HC groups (P = 0.183, P = 0.903, and P = 0.27, respectively). Serum IgG titers of SARS-CoV-2 neutralizing antibodies were significantly higher in patients who received two or more doses of inactivated vaccine than in patients who were unvaccinated or had received one dose of vaccine (244.36 ± 109.79 vs. 66.20 ± 82.50; P

Background: Obesity is one the most prevalent diseases all around the world. Some studies have shown a relationship between obesity and the worsening of rheumatic disorders. Higher rates of surgical complications might also be seen among these patients. Methods: This retrospective-descriptive study was performed on 25 patients with rheumatic disease referred to Loghman Hakim Hospital (Tehran- Iran) and candidates for bariatric surgery (laparoscopic Roux-en-Y gastric and laparoscopic sleeve gastrectomy) from 2018 to 2020. Duration of hospitalization after surgery and history of post-operation surgical and rheumatic complications were assessed. Patients were followed through 6 months after surgery. Results: The age (Mean±SD) of recruited patients was (38.4 ±10.0) years. The mean body mass index was 45.54 kg/m2 with the minimum and maximum values of 37.5 kg/m2 and 56.5 kg/m2. Among them, the prevalence of rheumatic disorders was rheumatoid arthritis 32%, psoriasis 28%, gout 16%, lupus erythematosus 8%, and other rheumatologic disorders 16%, respectively. One patient had a surgical complication that was a port site infection. One patient had a relapse of gout and other patients had remission and also, their therapeutic drugs were discontinued or reduced. Conclusion: Patients with rheumatic disorders revealed no higher surgical complication rate after bariatric surgery, and bariatric surgery helped disease remission among these patients.

Introduction: As a chronic autoimmune disease, Rheumatoid arthritis (RA) affects the joints. Studies have shown a complex and challenging link between cancer and RA. However, articles claim a significant relationship between cancer and treatment with DMARDs and biological DMARDs (e.g., Abatacept); however, the results are contradictory. Accordingly, this systematic review investigates the prevalence of cancer in RA patients taking Abatacept.Methods: We searched for articles published in four databases, namely Web of Science, Medline, PubMed, and Scopus up to September 29, 2023. The methodology followed recommendations from the Cochrane Handbook. During the search process, we selected articles using keywords such as “rheumatoid arthritis”, “malignancy”, and “cancer” with the Boolean operators “AND” and “OR”.”Results: A total of 12 studies were considered, the majority highlighted the effectiveness of Abatacept as an anti-RA medicine in the risk of cancer prevalence. Most of the patients investigated in the trials were female. Lung cancer was the greatest malignancy in those suffering from RA diseases. However, these investigations found no significant link between Abatacept use and cancer risk.Conclusion: There is speculation regarding the potential use of rheumatoid arthritis drugs in treating RA and its potential association with cancer incidence. According to the findings presented in this review article, there was no statistically significant association between the utilization of Abatacept and the prevalence of cancer in patients who were administered Abatacept either as a standalone treatment or in combination with other anti-rheumatoid medications. However, it is advised that further clinical trials be conducted to thoroughly investigate this association.

Objectives. To assess the lipid profile, neutrophil-lymphocyte ratio(NLR) and platelet-lymphocyte ratio(PLR) in different rheumatic diseases and to study their relation to disease activity and/or severity. Patients and methods. 257 patients (47 rheumatoid arthritis (RA), 100 systemic lupus erythematosus (SLE), 49 systemic sclerosis (SSc), 33 axial spondyloarthritis (axSpA) and 28 vasculitis (21with primary vasculitis and 7 with Behçet’s disease ‘BD’) and 70 controls were recruited. The disease activity and/or severity were assessed for each disease. The lipid profile was measured including: total cholesterol (TC), high-density lipoprotein (HDL),triglycerides (TG), low-density lipoprotein (LDL), very-low density lipoprotein (VLDL) and the LDL:HDL was calculated. The NLR and PLR were recorded. Results. In RA, NLR, PLR and HDL were significantly higher (p

Premature ovarian insufficiency (POI) is a clinical syndrome defined as loss of ovarian function before the age of 40 years. Among the causes of POI are genetic, metabolic disorders, as well as infectious or iatrogenic factors, but in some cases the exact cause cannot be established. Given the possible association of ovarian failure with autoimmune disorders, as well as the detection of antibodies to normal ovarian tissue in the serum of patients with POI, it is assumed that an autoimmune mechanism is a significant cause of the syndrome. Taking into account the relationship between POI and autoimmune diseases, it seems relevant to address the issues of mutual influence of the ovarian function of women with POI and rheumatic diseases (in particular, systemic lupus erythematosus, rheumatoid arthritis and systemic scleroderma), which is presented in this review. Hormone replacement therapy may be recommended for women with POI to improve their quality of life. Keywords: premature ovarian insufficiency, menopause, anti-ovarian antibodies, systemic lupus erythematosus, rheumatoid arthritis, systemic scleroderma, rheumatic diseases, hormone replacement therapy.

Cell-surface antigens, cytokines, receptors, and signal transduction molecules that are central in the pathogenesis of rheumatic diseases have been elucidated, and therapeutic targets have been identified. Molecular-targeted drugs are now available for the treatment of rheumatoid arthritis and other diseases, including psoriatic arthritis, ankylosing spondylitis, and juvenile idiopathic arthritis. These targeted drugs have shown the potential for achieving clinical remission in many rheumatic diseases. Tumor necrosis factor and interleukin-6 (IL-6) play major roles in rheumatoid arthritis, whereas IL-17 and IL-23 play crucial roles in spondyloarthritis. Biological disease-modifying anti-rheumatic drugs that specifically inhibit the actions of these cytokines and targeted synthetic disease-modifying anti-rheumatic drugs, such as Janus kinase inhibitors, have been approved, increasing the available treatment options. Molecular-targeted drugs also hold promise for the treatment of collagen diseases, including systemic lupus erythematosus, systemic sclerosis, and vasculitis. However, drawbacks related to their use persist, including high drug costs and the risk of adverse events, such as infectious diseases. Therefore, the criteria for selecting patients who are most likely to benefit from these drugs should be developed.

Telomeres, repetitive sequences located at the extremities of chromosomes, play a pivotal role in sustaining chromosomal stability. Telomerase is a complex enzyme that can elongate telomeres by appending telomeric repeats to chromosome ends and acts as a critical factor in telomere dynamics. The gradual shortening of telomeres over time is a hallmark of cellular senescence and cellular death. Notably, telomere shortening appears to result from the complex interplay of two primary mechanisms: telomere shelterin complexes and telomerase activity. The intricate interplay of genetic, environmental, and lifestyle influences can perturb telomere replication, incite oxidative stress damage, and modulate telomerase activity, collectively resulting in shifts in telomere length. This age-related process of telomere shortening plays a considerable role in various chronic inflammatory and oxidative stress conditions, including cancer, cardiovascular disease, and rheumatic disease. Existing evidence has shown that abnormal telomere shortening or telomerase activity abnormalities are present in the pathophysiological processes of most rheumatic diseases, including different disease stages and cell types. The impact of telomere shortening on rheumatic diseases is multifaceted. This review summarizes the current understanding of the link between telomere length and rheumatic diseases in clinical patients and examines probable telomere shortening in peripheral blood mononuclear cells and histiocytes. Therefore, understanding the intricate interaction between telomere shortening and various rheumatic diseases will help in designing personalized treatment and control measures for rheumatic disease.

Breakthrough COVID-19 (occurring in fully vaccinated people) has been described. Data on its characteristics among immune-mediated rheumatic disease (IMRD) patients are scarce. This study describes breakthrough COVID-19 occurring in IMRD patients participating in the SAFER-study, a Brazilian multicentric cohort evaluating the safety, effectiveness, and immunogenicity of SARS-CoV-2 vaccines in patients with autoimmune diseases. A descriptive analysis of the population and a binary logistic regression model were performed to evaluate the predictors of COVID-19-related hospitalization. A p-value < 0.05 was significant. The included 160 patients were predominantly females (83.1%), with a mean (SD) age of 40.23 (13.19) years. The patients received two (19%), three (70%), or four (11%) vaccine doses. The initial two-dose series was mainly with ChAdOx1 (Oxford/AstraZeneca) (58%) or BBIBP-CorV (Sinopharm-Beijing) (34%). The first booster (n = 150) was with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (63%) or ChAdOx1 (29%). The second booster (n = 112) was with BNT162b2 (40%) or ChAdOx1 (26%). The COVID-19 hospitalization rate was 17.5%. IMRD moderate/high activity (OR: 5.84; CI: 1.9–18.5; p = 0.002) and treatment with corticosteroids (OR: 2.94; CI: 1.02–8.49; p = 0.0043) were associated with higher odds of hospitalization, while increasing the number of vaccine doses was protective (OR: 0.37; CI: 0.15–0.9; p = 0.032). These findings, along with previous reassuring results about the safety of the COVID-19 vaccines, argue in favor of booster vaccination in IMRD patients.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by the presence of various serum autoantibodies and multi-system effects, predominantly affecting young female patients. The pathogenesis of SLE involves a combination of genetic factors, environmental triggers, and pathogen invasions that disrupt immune cell activation, leading to the release of autoantibodies and chronic inflammation. Mitochondria, as the primary cellular powerhouses, play a crucial role in SLE development through their control of energy generation, reactive oxygen species (ROS) production, and cellular apoptotic pathways. Dysregulation of mitochondrial structure and function can contribute to the immune dysregulation, oxidative stress, and inflammation seen in SLE. Recent research has highlighted the impact of mitochondrial dysfunction on various immune cells involved in SLE pathogenesis, such as T-lymphocytes, B-lymphocytes, neutrophils, and plasmacytoid dendritic cells. Mitochondrial dysfunction in these immune cells leads to increased ROS production, disrupted mitophagy, and alterations in energy metabolism, contributing to immune dysregulation and inflammation. Moreover, genetic variations in mitochondrial DNA (mtDNA) and abnormalities in mitochondrial dynamics have been linked to the pathogenesis of SLE, exacerbating oxidative stress and immune abnormalities. Targeting mitochondrial function has emerged as a promising therapeutic approach for SLE. Drugs such as sirolimus, N-acetylcysteine, coenzyme Q10, and metformin have shown potential in restoring mitochondrial homeostasis, reducing oxidative stress, and modulating immune responses in SLE. These agents have demonstrated efficacy in preclinical models and clinical studies by improving disease activity, reducing autoantibody titers, and ameliorating organ damage in SLE patients. In conclusion, this review underscores the critical role of mitochondria in the pathogenesis of SLE and the potential of targeting mitochondrial dysfunction as a novel therapeutic strategy for improving outcomes in SLE patients. Further investigation into the mechanisms underlying mitochondrial involvement in SLE and the development of targeted mitochondrial therapies hold promise for advancing SLE treatment and enhancing patient care.

Background: Patients with rheumatic diseases (RDs) have a lower desire to have children, fewer children, and a longer interval between their pregnancies, which can be due to the patient's personal choice, the physician's advice, changes in sexual activity, changes in fertility, and pregnancy failure. This study aimed to explore the understanding and experience of women with RDs regarding pregnancy intention. Method: In Mashhad, Northeast Iran, between December 2022 and March 2023, this qualitative inquiry was carried out. Purposive sampling was used to select thirty women with RDs. Semi-structured interviews were used to collect the data. Graneheim and Lundman's conventional content analysis method was used to analyze the data. The data organization was done using MAXQDA 12 software. Credibility, dependability, confirmability, and transferability have been considered as elements of trustworthiness. Results: The participants' data analysis revealed the following main theme: "duality of desire and fear in childbearing". Five main categories were identified, including "Individual health concerns following pregnancy", "motherhood and womanhood perceptions", "concerns about child harm", "contradictory beliefs and attitudes of significant family members and clinicians about pregnancy", and "lack of social support for fertility". Conclusion: In order to improve the outcomes of pregnancy for women with RDs, the medical professionals who manage them must actively and frequently inquire about their intentions to childbearing and offer them individualized guidance on how to be in the best possible health at the time of conception. Rheumatologists, gynecologists, and reproductive health specialists can better address the sexual and reproductive health needs of this population by enhancing their collaboration in the care of women with RDs. [ABSTRACT FROM AUTHOR]

This study investigated the association between autoimmunity and immunodeficiency in pediatric patients, focusing on the case of a 15-year-old female diagnosed with juvenile idiopathic arthritis (JIA) and secondary Sjögren's syndrome. The patient presented with a variety of symptoms, including joint pain, bronchial asthma, leukopenia, and skin lesions. Genetic testing revealed a de novo mutation in the DOCK8 gene, associated with DOCK8 deficiency, a condition usually associated with immunodeficiencies. The clinical course, diagnostic pathway, and treatment history are detailed, highlighting the importance of molecular diagnostics in understanding the genetic basis of rheumatic diseases. This case highlights the need to consider innate immune errors in patients with multiple diseases or atypical symptoms of rheumatic diseases. Furthermore, the study highlights the importance of targeted treatment, including genetic counseling, to improve patient outcomes. The observed association between autoimmunity and immune deficiency reinforces the importance of molecular testing in elucidating the causes of previously idiopathic rheumatic diseases, contributing to improved patient care and quality of life. [ABSTRACT FROM AUTHOR]

Background: Opioids are not recommended for fibromyalgia. Objective: To investigate the frequency of opioid use in a large cohort of fibromyalgia patients and to identify factors associated with opioid consumption. Methods: A retrospective, observational study of a large fibromyalgia cohort in a tertiary care center. We assessed fibromyalgia severity, functional capacity, anxiety, depression, drugs consumption and the patient's impression of change. We compared strong opioid consumers (SOC) and non-SOC. Inferential statistical and logistic regression analysis were used to identify factors associated with opioid consumption, and ANOVA for repeated measurements. Results: We found a prevalence of 9.2% of SOC (100 patients) among 1087 patients in the cohort. During the last four years there was a significant increase on the incidence of SOC up to 12.8% (p = 0.004). There were no differences in demographic variables between SOC and non-SOC. Clinical variables were significantly more severe in SOC, and they consumed more non-opioid drugs (p < 0.0001). Opioid consumption was independently associated with other non-opioid drugs (Odds ratio 1.25, CI: 1.13–1.38), but not with the fibromyalgia severity. At three months, 62% of the patients had opioid withdrawal. There were no statistical differences in the fibromyalgia severity at the initial evaluation, or the patient's impression of change compared with those patients who continued opioids. Coping strategies were better in those patients who withdrew opioids (p = 0.044). Conclusions: We observed an increase in opioid prescriptions during the last four years. Opioid consumption was associated with concomitant use of non-opioid drugs, but it was not associated with fibromyalgia severity. [ABSTRACT FROM AUTHOR]