Active juvenile systemic lupus erythematosus is associated with distinct NK cell transcriptional and phenotypic alterations.

While adaptive immune responses have been studied extensively in SLE (systemic lupus erythematosus), there is limited and contradictory evidence regarding the contribution of natural killer (NK) cells to disease pathogenesis. There is even less evidence about the role of NK cells in the more severe phenotype with juvenile-onset (J)SLE. In this study, analysis of the phenotype and function of NK cells in a large cohort of JSLE patients demonstrated that total NK cells, as well as perforin and granzyme A expressing NK cell populations, were significantly diminished in JSLE patients compared to age- and sex-matched healthy controls. The reduction in NK cell frequency was associated with increased disease activity, and transcriptomic analysis of NK populations from active and low disease activity JSLE patients versus healthy controls confirmed that disease activity was the main driver of differential NK cell gene expression. Pathway analysis of differentially expressed genes revealed an upregulation of interferon-α responses and a downregulation of exocytosis in active disease compared to healthy controls. Further gene set enrichment analysis also demonstrated an overrepresentation of the apoptosis pathway in active disease. This points to increased propensity for apoptosis as a potential factor contributing to NK cell deficiency in JSLE.

Phytosterols in human serum as measured using a liquid chromatography tandem mass spectrometry.

Phytosterols are lipophilic compounds found in plants with structural similarity to mammalian cholesterol. They cannot be endogenously produced by mammals and therefore always originate from diet. There has been increased interest in dietary phytosterols over the last few decades due to their association with a variety of beneficial health effects including low-density lipoprotein cholesterol lowering, anti-inflammatory and anti-cancerous effects. They are proposed as potential moderators for diseases associated with the central nervous system where cholesterol homeostasis is found to be imperative (multiple sclerosis, dementia, etc.) due to their ability to reach the brain. Here we utilised an enzyme-assisted derivatisation for sterol analysis (EADSA) in combination with a liquid chromatography tandem mass spectrometry (LC-MSn) to characterise phytosterol content in human serum. As little as 100 fg of plant sterol was injected on a reversed phase LC column. The method allows semi-quantitative measurements of phytosterols and their derivatives simultaneously with measurement of cholesterol metabolites. The identification of phytosterols in human serum was based on comparison of their LC retention times and MS2, MS3 spectra with a library of authentic standards. Free campesterol serum concentration was in the range from 0.30-4.10 µg/mL, ß-sitosterol 0.16-3.37 µg/mL and fucosterol was at lowest concentration range from 0.05-0.38 µg/mL in ten individuals. This analytical methodology could be applied to the analysis of other biological fluids and tissues.

Case study: the development of specialist nurse roles in Malta.

Specialist nurses play a significant role in healthcare. This study investigated and evaluated the primary and extended roles and the development of specialist nurses in Malta. METHODS: A qualitative case study design and purposive sampling techniques were used to gain a deep understanding of the complex issues surrounding specialist nurses from multiple data sets. A survey of the total specialist nurse population in 2013 (n=27), in-depth interviews with a group of specialist nurses (n=9) and four focus groups with key professionals and policy stakeholders (total n=28) were carried out. Data were collected between 2013 and 2015 and analysed using thematic analysis. FINDINGS: Three themes emerged: the roles and attributes of specialist nurses in Malta; the development of specialist nurses; and the influences on the advancement of specialist nursing practice in Malta. Although these data are nearly a decade old, no further research has been carried out. CONCLUSIONS: A legally accepted set of definitions as well as preparation and evaluation of the specialist nurse role from a national policy perspective is needed. Attitudes and systems that limit specialist nurses need to be challenged.

The Global Leadership Mentoring Community: An evaluation of its impact on nursing leadership.

AIM: To evaluate a year-long mentorship program, pairing nurses from different regions across the world to support their global leadership capability, and identifying additional consequences of their participation. BACKGROUND: Investment in developing nurse leaders continues as a strategic global imperative. Building on the first cohort's recommendations, this second program illustrates continued progress. PROGRAM EVALUATION: Using the logic model of program evaluation, this non-empirical paper uses data collected from anonymized questionnaires and participants' stories to help improve the program, illustrating innovative practices to develop the confidence and competence of emerging and established nurse leaders globally. DISCUSSION: The value of mentorship was recognized, and there were gains for both mentors and mentees in the development of leadership confidence and competence. Through engagement and collaboration with the whole community, participants were encouraged to understand their own and others' cultures avoiding assumptions and stereotypes. CONCLUSION: This evaluation illustrates that in addition to helping improve future programs, mentorship has enabled the growth of individuals' skill sets and the confidence to reach out to peers across the world to understand the meaning of global health and to make a meaningful contribution to the challenges they face. IMPLICATIONS FOR NURSING PRACTICE: Nurse managers should be encouraged to develop and formalize a mentoring culture to benefit the leadership competence and well-being of their workforce. IMPLICATIONS FOR NURSING POLICY: Every nurse has a responsibility to invest in nursing leadership for themselves and others. Mentorship can assist nurse leaders to build workforce capability to lead and contribute to the policy agenda locally, nationally, and internationally. Starting early and at the individual level, global mentorship programs can develop leadership expertise to help nurses find their voice and strengthen their confidence and competence to lead and therefore build the strategic leaders of the future.

Role of CD14+ monocyte-derived oxidised mitochondrial DNA in the inflammatory interferon type 1 signature in juvenile dermatomyositis.

OBJECTIVES: To define the host mechanisms contributing to the pathological interferon (IFN) type 1 signature in Juvenile dermatomyositis (JDM). METHODS: RNA-sequencing was performed on CD4+, CD8+, CD14+ and CD19+ cells sorted from pretreatment and on-treatment JDM (pretreatment n=10, on-treatment n=11) and age/sex-matched child healthy-control (CHC n=4) peripheral blood mononuclear cell (PBMC). Mitochondrial morphology and superoxide were assessed by fluorescence microscopy, cellular metabolism by 13C glucose uptake assays, and oxidised mitochondrial DNA (oxmtDNA) content by dot-blot. Healthy-control PBMC and JDM pretreatment PBMC were cultured with IFN-α, oxmtDNA, cGAS-inhibitor, TLR-9 antagonist and/or n-acetyl cysteine (NAC). IFN-stimulated gene (ISGs) expression was measured by qPCR. Total numbers of patient and controls for functional experiments, JDM n=82, total CHC n=35. RESULTS: Dysregulated mitochondrial-associated gene expression correlated with increased ISG expression in JDM CD14+ monocytes. Altered mitochondrial-associated gene expression was paralleled by altered mitochondrial biology, including 'megamitochondria', cellular metabolism and a decrease in gene expression of superoxide dismutase (SOD)1. This was associated with enhanced production of oxidised mitochondrial (oxmt)DNA. OxmtDNA induced ISG expression in healthy PBMC, which was blocked by targeting oxidative stress and intracellular nucleic acid sensing pathways. Complementary experiments showed that, under in vitro experimental conditions, targeting these pathways via the antioxidant drug NAC, TLR9 antagonist and to a lesser extent cGAS-inhibitor, suppressed ISG expression in pretreatment JDM PBMC. CONCLUSIONS: These results describe a novel pathway where altered mitochondrial biology in JDM CD14+ monocytes lead to oxmtDNA production and stimulates ISG expression. Targeting this pathway has therapeutical potential in JDM and other IFN type 1-driven autoimmune diseases.

Cytokine production by human B cells: role in health and autoimmune disease.

B cells are classically considered solely as antibody-producing cells driving humoral immune responses to foreign antigens in infections and vaccinations as well as self-antigens in pathological settings such as autoimmunity. However, it has now become clear that B cells can also secrete a vast array of cytokines, which influence both pro- and anti-inflammatory immune responses. Indeed, similarly to T cells, there is significant heterogeneity in cytokine-driven responses by B cells, ranging from the production of pro-inflammatory effector cytokines such as IL-6, through to the release of immunosuppressive cytokines such as IL-10. In this review, focusing on human B cells, we summarize the key findings that have revealed that cytokine-producing B cell subsets have critical functions in healthy immune responses and contribute to the pathophysiology of autoimmune diseases.

Gender-Diverse Inclusion in Immunological Research: Benefits to Science and Health.

The differences between male and female immune systems are an under-researched field, ripe for discovery. This is evidenced by the stark sex biases seen in autoimmunity and infectious disease. Both the sex hormones (oestrogen and testosterone), as well as the sex chromosomes have been demonstrated to impact immune responses, in multiple ways. Historical shortcomings in reporting basic and clinical scientific findings in a sex-disaggregated manner have led not only to limited discovery of disease aetiology, but to potential inaccuracies in the estimation of the effects of diseases or interventions on females and gender-diverse groups. Here we propose not only that research subjects should include both cis-gender men and cis-gender women, but also transgender and gender-diverse people alongside them. The known interaction between the hormonal milieu and the sex chromosomes is inseparable in cis-gender human research, without the confounders of puberty and age. By inclusion of those pursuing hormonal affirmation of their gender identity- the individual and interactive investigation of hormones and chromosomes is permitted. Not only does this allow for a fine-tuned dissection of these individual effects, but it allows for discovery that is both pertinent and relevant to a far wider portion of the population. There is an unmet need for detailed treatment follow-up of the transgender community- little is known of the potential benefits and risks of hormonal supplementation on the immune system, nor indeed on many other health and disease outcomes. Our research team has pioneered the inclusion of gender-diverse persons in our basic research in adolescent autoimmune rheumatic diseases. We review here the many avenues that remain unexplored, and suggest ways in which other groups and teams can broaden their horizons and invest in a future for medicine that is both fruitful and inclusive.

B cell contribution to immunometabolic dysfunction and impaired immune responses in obesity.

Obesity increases the risk of type 2 diabetes mellitus, cardiovascular disease, fatty liver disease, and cancer. It is also linked with more severe complications from infections, including COVID-19, and poor vaccine responses. Chronic, low-grade inflammation and associated immune perturbations play an important role in determining morbidity in people living with obesity. The contribution of B cells to immune dysregulation and meta-inflammation associated with obesity has been documented by studies over the past decade. With a focus on human studies, here we consolidate the observations demonstrating that there is altered B cell subset composition, differentiation, and function both systemically and in the adipose tissue of individuals living with obesity. Finally, we discuss the potential factors that drive B cell dysfunction in obesity and propose a model by which altered B cell subset composition in obesity underlies dysfunctional B cell responses to novel pathogens.

Mini-Review: Gut-Microbiota and the Sex-Bias in Autoimmunity - Lessons Learnt From Animal Models.

It is well appreciated that there is a female preponderance in the development of most autoimmune diseases. Thought to be due to a complex interplay between sex chromosome complement and sex-hormones, however, the exact mechanisms underlying this sex-bias remain unknown. In recent years, there has been a focus on understanding the central pathogenic role of the bacteria that live in the gut, or the gut-microbiota, in the development of autoimmunity. In this review, we discuss evidence from animal models demonstrating that the gut-microbiota is sexually dimorphic, that there is a bidirectional relationship between the production of sex-hormones and the gut-microbiota, and that this sexual dimorphism within the gut-microbiota may influence the sex-bias observed in autoimmune disease development. Collectively, these data underline the importance of considering sex as a variable when investigating biological pathways that contribute to autoimmune disease risk.

Investing in nursing and its leadership to secure global health: Are we making progress?

Investing in nursing and its leadership has been a key global priority in achieving world health. This paper aims to explore what it means to invest in nursing and its leadership and whether we are progressing in its endeavour. Consideration is given to whose responsibility it is to invest, the importance of education to support strategic nurse leaders and enable them to have a voice to lead as well as create a culture in which their staff wish to stay. Further, the paper explores the importance of each country accepting responsibility for developing and funding its strategic workforce plan and paying nurse professionals fairly and taking steps to reduce workforce shortages. Finally, the paper examines the progress the United Kingdom is making and concludes that investment in nursing is everyone's business, the government, healthcare organisations, society and above all nurses themselves. Collectively, we must step up to influence change and have nursing voices heard.

Favorable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases.

BACKGROUND: Differences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained, and the effect of underlying immune dysfunction or suppression is unknown. Here, we sought to examine the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), and juvenile systemic lupus erythematosus (JSLE) against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group. METHODS: Sera were collected from JIA (n = 118), JDM (n = 49), and JSLE (n = 30) patients and from healthy control (n = 54) children and adolescents prior to the coronavirus disease 19 (COVID-19) pandemic. We used sensitive flow-cytometry-based assays to determine titers of antibodies that reacted with the spike and nucleoprotein of HCoV-OC43 and cross-reacted with the spike and nucleoprotein of SARS-CoV-2, and we compared them with respective titers in sera from patients with multisystem inflammatory syndrome in children and adolescents (MIS-C). FINDINGS: Despite immune dysfunction and immunosuppressive treatment, JIA, JDM, and JSLE patients maintained comparable or stronger humoral responses than healthier peers, which was dominated by immunoglobulin G (IgG) antibodies to HCoV-OC43 spike, and harbored IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM, and JSLE patients, which argues against increased exposure. CONCLUSIONS: Consequently, autoimmune rheumatic diseases and their treatment were associated with a favorable ratio of spike to nucleoprotein antibodies. FUNDING: This work was supported by a Centre of Excellence Centre for Adolescent Rheumatology Versus Arthritis grant, 21593, UKRI funding reference MR/R013926/1, the Great Ormond Street Children's Charity, Cure JM Foundation, Myositis UK, Lupus UK, and the NIHR Biomedical Research Centres at GOSH and UCLH. This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council, and the Wellcome Trust.

Biomarkers Associated with Organ-Specific Involvement in Juvenile Systemic Lupus Erythematosus.

Juvenile systemic lupus erythematosus (JSLE) is characterised by onset before 18 years of age and more severe disease phenotype, increased morbidity and mortality compared to adult-onset SLE. Management strategies in JSLE rely heavily on evidence derived from adult-onset SLE studies; therefore, identifying biomarkers associated with the disease pathogenesis and reflecting particularities of JSLE clinical phenotype holds promise for better patient management and improved outcomes. This narrative review summarises the evidence related to various traditional and novel biomarkers that have shown a promising role in identifying and predicting specific organ involvement in JSLE and appraises the evidence regarding their clinical utility, focusing in particular on renal biomarkers, while also emphasising the research into cardiovascular, haematological, neurological, skin and joint disease-related JSLE biomarkers, as well as genetic biomarkers with potential clinical applications.

Intestinal barrier dysfunction plays an integral role in arthritis pathology and can be targeted to ameliorate disease.

BACKGROUND: Evidence suggests an important role for gut-microbiota dysbiosis in the development of rheumatoid arthritis (RA). The link between changes in gut bacteria and the development of joint inflammation is missing. Here, we address whether there are changes to the gut environment and how they contribute to arthritis pathogenesis. METHODS: We analyzed changes in markers of gut permeability, damage, and inflammation in peripheral blood and serum of RA patients. Serum, intestines, and lymphoid organs isolated from K/BxN mice with spontaneous arthritis or from wild-type, genetically modified interleukin (IL)-10R-/-or claudin-8-/-mice with induced arthritis were analyzed by immunofluorescence/histology, ELISA, and flow cytometry. FINDINGS: RA patients display increased levels of serum markers of gut permeability and damage and cellular gut-homing markers, both parameters positively correlating with disease severity. Arthritic mice display increased gut permeability from early stages of disease, as well as bacterial translocation, inflammatory gut damage, increases in interferon γ (IFNγ)+and decreases in IL-10+intestinal-infiltrating leukocyte frequency, and reduced intestinal epithelial IL-10R expression. Mechanistically, both arthritogenic bacteria and leukocytes are required to disrupt gut-barrier integrity. We show that exposing intestinal organoids to IFNγ reduces IL-10R expression by epithelial cells and that mice lacking epithelial IL-10R display increased intestinal permeability and exacerbated arthritis. Claudin-8-/-mice with constitutively increased gut permeability also develop worse joint disease. Treatment of mice with AT-1001, a molecule that prevents development of gut permeability, ameliorates arthritis. CONCLUSIONS: We suggest that breakdown of gut-barrier integrity contributes to arthritis development and propose restoration of gut-barrier homeostasis as a new therapeutic approach for RA. FUNDING: Funded by Versus Arthritis (21140 and 21257) and UKRI/MRC (MR/T000910/1).

The emerging field of regulatory B cell immunometabolism.

B cells are well known as critical mediators of humoral immune responses via the production of antibodies. However, numerous studies have also identified populations of B cells that are characterized by their anti-inflammatory properties. These "regulatory B cells" restrain excessive inflammatory responses in a wide range of health conditions. A significant knowledge gap remains concerning the nature of the signals that determine whether a B cell exerts a pro-inflammatory or anti-inflammatory function. In this perspective, we explore the concept that in addition to the cytokine microenvironment, intracellular and extracellular metabolic signals play a pivotal role in controlling the balance between regulatory and antibody-producing B cell subsets. Determining the metabolites and tissue-specific signals that influence B cell fate could establish novel therapeutic targets for the treatment of diseases where abnormal B cell responses contribute to pathogenesis.

Reflexões: a responsabilidade das enfermeiras com doutorado de liderar uma mudança na prática / Reflexiones: la responsabilidad de las enfermeras con doctorado de liderar un cambio en la práctica / Reflections: The Responsibility of Doctoral Nurses to Lead a Change in Practice

This paper aims to consider the responsibilities of doctoral nurses to lead changes in practice through a very personal reflection of over 52 years in nursing. The reflective learning moves from an early training experience where I learned to 'do' to becoming a nursing professor with a doctoral qualification and an 'evidence-based doer.' The change witnessed has been considerable. As the highest educated professional, I have learned that doctoral nurses are responsible for leading and directly influencing clinical practice, either as a practitioner, an educator, or a researcher. They are capable of encouraging the development of critical thinking skills and helping practitioners to be curious, take risks with ideas, identify gaps in the evidence base, and be creative in their problem-solving. If the strategic vision for nurses globally is to provide the best quality of patient care, then evidence-based practice is key to leading from the head, hand, and heart. Doctoral nurses understand the patient benefits of a high staff-to-patient ratio and having a critical mass of university qualified nurses and must strive to influence policy to this effect. As each country, particularly in Latin America, develops a critical mass of doctorally qualified nurses, then they can harness their innovation, create new ways of working, attract them back into practice, and strengthen their political voice to lead strategic change. Doctoral nurses must develop their leadership skills and their confidence to lead. They have a responsibility to realise their potential and identify the opportunities to really make a difference.

El presente artículo tiene como objetivo considerar las responsabilidades de las enfermeras con doctorado de liderar cambios en la práctica a través de una reflexión muy personal de mis más de 52 años de experiencia en enfermería. El aprendizaje reflexivo transita de una experiencia de formación temprana en la que aprendí a "hacer" a convertirme en una profesora de enfermería con un título de doctorado y en una enfermera que actúa "con base en la evidencia". El cambio que he observado ha sido enorme. Como profesional con el más alto nivel educativo, he aprendido que las enfermeras con doctorado son responsables de liderar e influir directamente en la práctica clínica, ya sea como practicantes, educadoras o investigadoras, pues son capaces de fomentar el desarrollo de habilidades de pensamiento crítico y de ayudar a las practicantes a ser curiosas, a tomar riesgos en las ideas, a identificar lagunas en la evidencia y a ser creativas en la resolución de problemas. Si la visión estratégica de las enfermeras a nivel mundial es brindar la mejor calidad de atención al paciente, entonces la práctica basada en la evidencia es clave para liderar desde la cabeza, la mano y el corazón. Las enfermeras con doctorado comprenden los beneficios de contar tanto con una alta proporción de personal por paciente como con una masa crítica de enfermeras con título universitario y, por lo tanto, deben esforzarse por influir en las políticas para este fin. A medida que cada país, en particular en América Latina, desarrolla una masa crítica de enfermeras con doctorado, puede aprovechar su innovación, crear nuevas formas de trabajo, atraerlas nuevamente a la práctica y fortalecer su voz política para liderar el cambio estratégico. Las enfermeras con doctorado deben desarrollar sus habilidades de liderazgo y su confianza para liderar, puesto que tienen la responsabilidad de desarrollar su potencial e identificar las oportunidades para marcar la diferencia.

O objetivo deste artigo é identificar as responsabilidades das enfermeiras com doutorado de liderar mudanças na prática por meio de uma reflexão pessoal com base nos meus 52 anos de experiência em enfermagem. A aprendizagem reflexiva transita de uma experiência de formação precoce na qual aprendi a "fazer", a me tornar uma professora de enfermagem com título de doutorado e uma enfermeira que atua com base na evidência. A mudança que venho observando é enorme. Como profissional com mais alto nível educacional, aprendi que as enfermeiras com doutorado são as responsáveis por liderar e influenciar diretamente a prática clínica, seja como profissionais da saúde, seja como educadoras ou pesquisadoras, pois são capazes de fomentar o desenvolvimento de habilidades de pensamento crítico e de ajudar as profissionais da saúde a serem curiosas, a correr riscos com suas ideias, a identificar lacunas na evidência e a buscar solução de problemas. Se a visão estratégica das enfermeiras no âmbito mundial é oferecer melhor qualidade de atenção ao paciente, então a prática baseada na evidência é fundamental para liderar a partir da cabeça, da mão e do coração. As enfermeiras com doutorado compreendem os benefícios de contar tanto com uma alta proporção de pessoal por paciente quanto com um corpus crítico de enfermeiras com título universitário e, portanto, devem se esforçar por influenciar as políticas para esse objetivo. À medida que cada país, em particular na América Latina, desenvolve um corpus crítico de enfermeiras com doutorado, pode aproveitar sua inovação, criar formas de trabalho, atraí-las novamente para a prática e fortalecer sua voz política para liderar a mudança estratégia. As enfermeiras doutoras devem desenvolver suas habilidades de lideranças e sua confiança para liderar, visto que têm a responsabilidade de desenvolver seu potencial e identificar as oportunidades para fazer a diferença.

A systematic review exploring the bidirectional relationship between puberty and autoimmune rheumatic diseases.

BACKGROUND: Autoimmune rheumatic diseases (ARDs) are associated with a significant sex-bias, which becomes more evident post-puberty. This systematic review aims to elucidate the bidirectional relationship between puberty and ARD-related outcomes. METHODS: Studies published in English until October 2019 were identified using a systematic search of endocrinology and rheumatology literature. Information was extracted on study design, sample size, demographics, puberty outcome measures, disease outcome measures, and main findings. The methodological quality of the studies included was analysed using the Newcastle-Ottawa Scale (NOS). RESULTS: Sixteen non-randomised studies reporting on the impact of puberty on ARD outcomes (n = 7), ARD impact on puberty-related outcomes (n = 8), or both (n = 1) have been identified. The impact of puberty on ARD outcomes were investigated in patients with juvenile idiopathic arthritis (JIA)-associated uveitis (n = 1), juvenile systemic lupus erythematosus (JSLE) (n = 5) or in healthy controls who developed adult-onset SLE (n = 1) or had non-specific symptoms (n = 1). The impact of ARD on puberty outcomes was explored in JIA (n = 4) and JSLE (n = 3). Quality assessment of studies showed a small to moderate risk of bias overall (NOS 4-9/9). Due to large heterogeneity of the studies it was not possible to perform a meta-analysis. Multiple studies reported on delayed puberty in patients with JIA/JSLE, menstrual and hormonal abnormalities, and lower height and weight than controls. Earlier (pre-pubertal) onset of JSLE was correlated with more severe disease and more need for systemic treatment. CONCLUSION: A bidirectional relationship exists between puberty and ARDs; however, more and better research is required to elucidate the complexity of this relationship. We propose puberty-related clinical assessments in patients with ARDs, which can improve patient outcomes and facilitate future research.

Regulatory B Cells in Experimental Mouse Models of Arthritis.

Regulatory B cells (Breg) have been shown to have a role in the suppression of a wide variety of immune responses, yet they are deficient or defective in autoimmune diseases such as rheumatoid arthritis. For the study of autoimmune inflammation, experimental models of arthritis have acted as a valuable tool in understanding the development of Bregs and their role in maintaining immune homeostasis. In this chapter, we will focus on the study of transitional-2 marginal zone precursor (T2-MZP) Bregs in the context of two experimental arthritis models: antigen-induced arthritis (AIA) and collagen-induced arthritis (CIA). We will specifically focus on how to induce arthritis, as well as on methods for the isolation and functional study of Bregs both in vitro and in vivo.

Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission.

Anecdotal evidence suggests that Coronavirus disease 2019 (COVID-19), caused by the coronavirus SARS-CoV-2, exhibits differences in morbidity and mortality between sexes. Here, we present a meta-analysis of 3,111,714 reported global cases to demonstrate that, whilst there is no difference in the proportion of males and females with confirmed COVID-19, male patients have almost three times the odds of requiring intensive treatment unit (ITU) admission (OR = 2.84; 95% CI = 2.06, 3.92) and higher odds of death (OR = 1.39; 95% CI = 1.31, 1.47) compared to females. With few exceptions, the sex bias observed in COVID-19 is a worldwide phenomenon. An appreciation of how sex is influencing COVID-19 outcomes will have important implications for clinical management and mitigation strategies for this disease.