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There is a large and growing body of literature proposing that there are benefits to employees and workplaces when pets are allowed to accompany their owners to work. This article reports a scoping review of research that is workplace-based and that provides information on the reported benefits or problems of allowing employees' pets at work. The databases Scopus, Discover and Google Scholar were searched with the initial search terms "pets AND workplace AND research." Results were reviewed initially by title to remove items where, for instance, "PET" was used as an acronym. Studies were included if they provided information on research into human well-being and/or work or task performance and pets at work. This included research into the presence of pets while working from home, as the home can be considered a workplace in this situation. A total of 189 papers on pets at work were identified from the searches. The abstracts were reviewed and papers that did not report research into the benefits and challenges of employees' pets at work were excluded, leaving 31 results. The majority of studies used survey methods and did not include validated psychometric measures of key variables including stress. Findings indicated that the presence of employees' pets at work may reduce stress and lead to more positive work-related attitudes, but these findings may not apply to all employees or all workplaces. Negative aspects of pets in the workplace include health risks to humans and animals, cultural concerns and dislike or fear of some animals, and the proportion of participants who raised these concerns or agreed with them varied widely between studies. However, there is little evidence on the prevalence of risks or how they are addressed, and there was no data on how work performance, absenteeism or staff turnover were related to pet-friendly policies at work. More research is required, and some directions for future research are suggested. [ABSTRACT FROM AUTHOR]

AIM: To examine the relationships between workplace bullying, destructive leadership and team conflict, and physical health, strain, self-reported performance and intentions to quit among veterinarians in New Zealand, and how these relationships could be moderated by psychological capital and perceived organisational support. METHODS: Data were collected by means of an online survey, distributed to members of the New Zealand Veterinary Association. Participation was voluntary and all responses were anonymous and confidential. Scores for the variables measured were based on responses to questions or statements with responses categorised on a linear scale. A series of regression analyses were used to assess mediation or moderation by intermediate variables on the relationships between predictor variables and dependent variables. RESULTS: Completed surveys were provided by 197 veterinarians, of which 32 (16.2%) had been bullied at work, i.e. they had experienced two or more negative acts at least weekly over the previous 6 months, and nine (4.6%) had experienced cyber-bullying. Mean scores for workplace bullying were higher for female than male respondents, and for non-managers than managers (p<0.01). Scores for workplace bullying were positively associated with scores for destructive leadership and team conflict, physical health, strain, and intentions to quit (p<0.001). Workplace bullying and team conflict mediated the relationship between destructive leadership and strain, physical health and intentions to quit. Perceived organisational support moderated the effects of workplace bullying on strain and self-reported job performance (p<0.05). CONCLUSIONS: Relatively high rates of negative behaviour were reported by veterinarians in this study, with 16% of participants meeting an established criterion for having been bullied. The negative effects of destructive leadership on strain, physical health and intentions to quit were mediated by team conflict and workplace bullying. It should be noted that the findings of this study were based on a survey of self-selected participants and the findings may not represent the wider population of New Zealand veterinarians. [ABSTRACT FROM PUBLISHER]

Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal and spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren's disease and Sicca Syndrome, with ex-vivo functional studies to construct a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures. We confirm the presence of a fibroblast cell state and identify a pericyte/mural cell state with potential immunological functions. The identification of cellular properties associated with these structures and the molecular and functional interactions identified by this analysis may provide key therapeutic cues for tertiary lymphoid structures associated conditions in autoimmunity and cancer., Competing Interests: Competing interests: F.B. is an employee of Candel Therapeutics. C.D.B is the founder of Mestag Therapeutics. B.A.F. has undertaken consultancy for: Novartis, BMS, Servier, Galapagos, Roche, UCB, Sanofi, Janssen, A.Z., Otsuka, Amgen, Kiniksa and received research funding from Janssen, Servier, Galapagos, and Celgene. A.F. has consulted for Janssen and Sonoma, and has received research funding from: BMS, Roche, UCB, Nascient, Mestag, GSK, and Janssen. S.J.B. has undertaken consultancy for: Abbvie, Amgen, Argenx, Aurinia, Bain, BMS, EcoR1, Iqvia, J&J/Janssen, Kiniksa & Novartis. K.G.L. and A.P.F. are employees of F. Hoffmann-La Roche Ltd. The remaining authors declare no competing interests., (© 2024. The Author(s).)

First-year veterinary students' perceptions on the veterinary professionalism attributes important to future success in clinical practice were explored using a card sort technique. The key findings were that self-oriented attributes (overall mean: 3.20; 42% of responses rated essential) and people-oriented attributes (overall mean: 3.13; 39% essential) were rated more highly than task-oriented attributes (overall mean: 2.98; 31% essential) (1-4 scale: 1 = irrelevant, 4 = essential). Within these overall ratings, the establishment/maintenance of effective client relationships (people-oriented attribute; mean: 3.84) and the ability to be composed under pressure and recover quickly (self-oriented attribute; mean: 3.82) received the highest scores. The highest task-oriented score was the ability to work to a high standard and achieve results (mean: 3.57). There was no difference between ethnicities or between men and women, but respondents < 20 years of age gave higher scores to people-oriented attributes than did older respondents (≥ 20 years). The use of the card sort technique has not been widely reported in veterinary educational literature, and so this study represents a novel approach to garnering opinions from newly enrolled veterinary students-a group of stakeholders whose views on this subject are seldom sought. The results show that first-year veterinary students have well-developed opinions on the key attributes of veterinary professionalism and indicate that the early development of students' opinions needs to be taken into consideration in the design of professionalism curricula within veterinary programs.

BACKGROUNDPrimary Sjögren's syndrome (pSS) is characterized by B cell hyperactivity and elevated B-lymphocyte stimulator (BLyS). Anti-BLyS treatment (e.g., belimumab) increases peripheral memory B cells; decreases naive, activated, and plasma B cell subsets; and increases stringency on B cell selection during reconstitution. Anti-CD20 therapeutics (e.g., rituximab) bind and deplete CD20-expressing B cells in circulation but are less effective in depleting tissue-resident CD20+ B cells. Combined, these 2 mechanisms may achieve synergistic effects.METHODSThis 68-week, phase II, double-blind study (GSK study 201842) randomized 86 adult patients with active pSS to 1 of 4 arms: placebo, s.c. belimumab, i.v. rituximab, or sequential belimumab + rituximab.RESULTSOverall, 60 patients completed treatment and follow-up until week 68. The incidence of adverse events (AEs) and drug-related AEs was similar across groups. Infections/infestations were the most common AEs, and no serious infections of special interest occurred. Near-complete depletion of minor salivary gland CD20+ B cells and a greater and more sustained depletion of peripheral CD19+ B cells were observed with belimumab + rituximab versus monotherapies. With belimumab + rituximab, reconstitution of peripheral B cells occurred, but it was delayed compared with rituximab. At week 68, mean (± standard error) total EULAR Sjögren's syndrome disease activity index scores decreased from 11.0 (1.17) at baseline to 5.0 (1.27) for belimumab + rituximab and 10.4 (1.36) to 8.6 (1.57) for placebo.CONCLUSIONThe safety profile of belimumab + rituximab in pSS was consistent with the monotherapies. Belimumab + rituximab induced enhanced salivary gland B cell depletion relative to the monotherapies, potentially leading to improved clinical outcomes.TRIAL REGISTRATIONClinicalTrials.gov NCT02631538.FUNDINGFunding was provided by GSK.

Immunofibroblasts have been described within tertiary lymphoid structures (TLS) that regulate lymphocyte aggregation at sites of chronic inflammation. Here we report, for the first time, an immunoregulatory property of this population, dependent on inducible T-cell co-stimulator ligand and its ligand (ICOS/ICOS-L). During inflammation, immunofibroblasts, alongside other antigen presenting cells, like dendritic cells (DCs), upregulate ICOSL, binding incoming ICOS + T cells and inducing LTα3 production that, in turn, drives the chemokine production required for TLS assembly via TNFRI/II engagement. Pharmacological or genetic blocking of ICOS/ICOS-L interaction results in defective LTα expression, abrogating both lymphoid chemokine production and TLS formation. These data provide evidence of a previously unknown function for ICOSL-ICOS interaction, unveil a novel immunomodulatory function for immunofibroblasts, and reveal a key regulatory function of LTα3, both as biomarker of TLS establishment and as first driver of TLS formation and maintenance in mice and humans., (© 2022. The Author(s).)

Background: While previous research has examined components of professionalism that veterinary employers and clients expect in veterinarians, little attention has been paid to practising clinical veterinarians' opinions on important professional competencies that help to enhance the veterinarian-client relationship. This study used a phenomenological approach and critical incident technique to gather the narratives of practising veterinarians in New Zealand about positive and negative veterinarian-client interactions. The intention was to identify the underlying principles of professionalism that resulted in the positive/negative outcomes of those interactions., Methods: Twenty-two practising veterinarians were interviewed, and each respondent was asked to recollect and narrate a significant positive and a significant negative critical incident in their career that involved a veterinarian-client interaction within a clinical setting. The professional competencies that the veterinarian believed contributed to a successful or an unsuccessful outcome were elucidated using thematic analysis., Results: Thematic analysis of the critical incident narratives revealed four major themes under the overarching theme of 'building a relationship between the veterinarian and the client': 'accountability and integrity', 'effective communication skills', 'personal wellbeing' and 'quality of care'., Conclusion: The description of the important professional competencies that helped to enhance the veterinarian-client relationship provides a reference for the practising profession to help improve the likelihood of veterinarians enjoying satisfied and successful careers., (© 2021 British Veterinary Association.)

CD80 and CD86 are expressed on antigen presenting cells (APCs) and their role in providing costimulation to T cells is well established. However, it has been shown that these molecules can also be expressed by T cells, but the significance of this observation remains unknown. We have investigated stimuli that control CD80 and CD86 expression on T cells and show that in APC-free conditions around 40% of activated, proliferating CD4 + T cells express either CD80, CD86 or both. Expression of CD80 and CD86 was strongly dependent upon provision of CD28 costimulation as ligands were not expressed following TCR stimulation alone. Furthermore, we observed that CD80 + T cells possessed the hallmarks of induced regulatory T cells (iTreg), expressing Foxp3 and high levels of CTLA-4 whilst proliferating less extensively. In contrast, CD86 was preferentially expressed on INF-γ producing cells, which proliferated more extensively and had characteristics of effector T cells. Finally, we demonstrated that CD80 expressed on T cells inhibits CTLA-4 function and facilitates the growth of iTreg. Together these data establish endogenous expression of CD80 and CD86 by activated T cells is not due to ligand capture by transendocytosis and highlight clear differences in their expression patterns and associated functions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Soskic, Jeffery, Kennedy, Gardner, Hou, Halliday, Williams, Janman, Rowshanravan, Hirschfield and Sansom.)

CD40 and its ligand CD40L (CD154) belong to the tumor necrosis factor receptor superfamily and are expressed by a variety of immune and non-immune cells. CD40L plays a central role in co-stimulation and regulation of the immune response via activation of cells expressing CD40. Imbalance of the CD40-CD40L co-stimulatory pathway has been reported in many autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome, thus supporting its role in the breach of immune tolerance that is typical of these diseases. Targeting CD40-CD40L signalling might represent a novel therapeutic option for several autoimmune disorders., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earliest phases of TLS establishment. This program of events, that precedes lymphocyte infiltration in the tissue, is mediated by paracrine and autocrine signals mainly regulated by IL13. This initial fibroblast network is expanded and stabilized, once lymphocytes are recruited, by the local production of the cytokines IL22 and lymphotoxin. Interfering with this regulated program of events or depleting the immunofibroblasts in vivo results in abrogation of local pathology, demonstrating the functional role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel therapeutic targets in TLS-associated diseases., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Background: The phosphatidylinositol 3-kinase delta isoform (PI3Kδ) belongs to an intracellular lipid kinase family that regulate lymphocyte metabolism, survival, proliferation, apoptosis and migration and has been successfully targeted in B-cell malignancies. Primary Sjögren's syndrome (pSS) is a chronic immune-mediated inflammatory disease characterised by exocrine gland lymphocytic infiltration and B-cell hyperactivation which results in systemic manifestations, autoantibody production and loss of glandular function. Given the central role of B cells in pSS pathogenesis, we investigated PI3Kδ pathway activation in pSS and the functional consequences of blocking PI3Kδ in a murine model of focal sialoadenitis that mimics some features of pSS., Methods and Results: Target validation assays showed significant expression of phosphorylated ribosomal protein S6 (pS6), a downstream mediator of the phosphatidylinositol 3-kinase delta (PI3Kδ) pathway, within pSS salivary glands. pS6 distribution was found to co-localise with T/B cell markers within pSS aggregates and the CD138+ plasma cells infiltrating the glands. In vivo blockade of PI3Kδ activity with seletalisib, a PI3Kδ-selective inhibitor, in a murine model of focal sialoadenitis decreased accumulation of lymphocytes and plasma cells within the glands of treated mice in the prophylactic and therapeutic regimes. Additionally, production of lymphoid chemokines and cytokines associated with ectopic lymphoneogenesis and, remarkably, saliva flow and autoantibody production, were significantly affected by treatment with seletalisib., Conclusion: These data demonstrate activation of PI3Kδ pathway within the glands of patients with pSS and its contribution to disease pathogenesis in a model of disease, supporting the exploration of the therapeutic potential of PI3Kδ pathway inhibition in this condition., Competing Interests: Competing interests: SN, Grant/Research support: UCB Pharma; RAA, WAF, AP Employee of UCB Pharma. FB, Grant/Research support, ARUK., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

Tertiary lymphoid structures (TLS) are frequently observed in target organs of autoimmune diseases. TLS present features of secondary lymphoid organs such as segregated T and B cell zones, presence of follicular dendritic cell networks, high endothelial venules and specialized lymphoid fibroblasts and display the mechanisms to support local adaptive immune responses toward locally displayed antigens. TLS detection in the tissue is often associated with poor prognosis of disease, auto-antibody production and malignancy development. This review focuses on the contribution of TLS toward the persistence of the inflammatory drive, the survival of autoreactive lymphocyte clones and post-translational modifications, responsible for the pathogenicity of locally formed autoantibodies, during autoimmune disease development.

Tertiary lymphoid structures (TLS) are organized aggregates of lymphocytes, myeloid, and stromal cells that provide ectopic hubs for acquired immune responses. TLS share phenotypical and functional features with secondary lymphoid organs (SLO); however, they require persistent inflammatory signals to arise and are often observed at target sites of autoimmune disease, chronic infection, cancer, and organ transplantation. Over the past 10 years, important progress has been made in our understanding of the role of stromal fibroblasts in SLO development, organization, and function. A complex and stereotyped series of events regulate fibroblast differentiation from embryonic life in SLOs to lymphoid organ architecture observed in adults. In contrast, TLS-associated fibroblasts differentiate from postnatal, locally activated mesenchyme, predominantly in settings of inflammation and persistent antigen presentation. Therefore, there are critical differences in the cellular and molecular requirements that regulate SLO versus TLS development that ultimately impact on stromal and hematopoietic cell function. These differences may contribute to the pathogenic nature of TLS in the context of chronic inflammation and malignant transformation and offer a window of opportunity for therapeutic interventions in TLS associated pathologies.

Lymphangiogenesis associated with tertiary lymphoid structure (TLS) has been reported in numerous studies. However, the kinetics and dynamic changes occurring to the lymphatic vascular network during TLS development have not been studied. Using a viral-induced, resolving model of TLS formation in the salivary glands of adult mice we demonstrate that the expansion of the lymphatic vascular network is tightly regulated. Lymphatic vessel expansion occurs in two distinct phases. The first wave of expansion is dependent on IL-7. The second phase, responsible for leukocyte exit from the glands, is regulated by lymphotoxin (LT)βR signaling. These findings, while highlighting the tight regulation of the lymphatic response to inflammation, suggest that targeting the LTα1β2/LTβR pathway in TLS-associated pathologies might impair a natural proresolving mechanism for lymphocyte exit from the tissues and account for the failure of therapeutic strategies that target these molecules in diseases such as rheumatoid arthritis., (Copyright © 2016 The Authors.)

Inhibition of the CD28:CD80/CD86 T cell costimulatory pathway has emerged as an effective strategy for the treatment of T cell-mediated inflammatory diseases. However, patient responses to CD28-ligand blockade by abatacept (CTLA-4-Ig) in conditions such as rheumatoid arthritis are variable and often suboptimal. In this study, we show that the extent to which abatacept suppresses T cell activation is influenced by the strength of TCR stimulation, with high-strength TCR stimulation being associated with relative abatacept insensitivity. Accordingly, cyclosporin A, an inhibitor of T cell stimulation via the TCR, synergized with abatacept to inhibit T cell activation. We also observed that 1,25-dihydroxyvitamin D3 enhanced the inhibition of T cell activation by abatacept, strongly inhibiting T cell activation driven by cross-linked anti-CD3, but with no effect upon anti-CD28 driven stimulation. Thus, like cyclosporin A, 1,25-dihydroxyvitamin D3 inhibits TCR-driven activation, thereby promoting abatacept sensitivity. Vitamin D3 supplementation may therefore be a useful adjunct for the treatment of conditions such as rheumatoid arthritis in combination with abatacept to promote the efficacy of treatment., (Copyright © 2015 The Authors.)

A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging molecules have been implicated within the complex sequential processes that result in phagocytosis and degradation of apoptotic cells. Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance, although its precise role in the clearance process is ill defined. The main objective of this work is to further characterise the function of ICAM-3 in the removal of apoptotic cells. Using a range of novel anti-ICAM-3 monoclonal antibodies (mAbs), including one (MA4) that blocks apoptotic cell clearance by macrophages, alongside apoptotic human leukocytes that are normal or deficient for ICAM-3, we demonstrate that ICAM-3 promotes a domain 1-2-dependent tethering interaction with phagocytes. Furthermore, we demonstrate an apoptosis-associated reduction in ICAM-3 that results from release of ICAM-3 within microparticles that potently attract macrophages to apoptotic cells. Taken together, these data suggest that apoptotic cell-derived microparticles bearing ICAM-3 promote macrophage chemoattraction to sites of leukocyte cell death and that ICAM-3 mediates subsequent cell corpse tethering to macrophages. The defined function of ICAM-3 in these processes and profound defect in chemotaxis noted to ICAM-3-deficient microparticles suggest that ICAM-3 may be an important adhesion molecule involved in chemotaxis to apoptotic human leukocytes.

Optimism, self-esteem, satisfaction with social support, and coping strategies were examined in relation to study-related subjective workload, stress, and life satisfaction. Questionnaires were distributed to students in the second, third, and fourth years of the five-year BVSc program at Massey University. One hundred fifty usable responses were received. Most respondents were female. Students with more optimism and self-esteem were less stressed than those who were more pessimistic or lower in self-esteem. Students who reported having heavy subjective workloads were more stressed, whereas students with higher self-esteem experienced more well-being. Men and women did not differ on any of the study variables, and there were no differences between students in different years of study. Recommendations include retaining initiatives to build well-being that are already in place. Support resources exist within the university, but students are often reluctant to seek help, so staff need to continue to identify students in need of additional help who might benefit from referral to a health practitioner. Where practicable, support service providers may be able to contribute actively to teaching. As well as helping students build effective social and coping strategies, this approach will provide students with additional information about the services that are available. Students may not see workshops on interpersonal skills or stress management as relevant unless they are linked to their immediate concerns.