Search results
Found 30540 matches for
T cell phenotypes in COVID-19 - a living review.
COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients' long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation.
2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.
OBJECTIVES: Fatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage. The existence of multiple factors associated with driving and maintaining fatigue, and the evidence about what improves fatigue has led to a multifaceted approach to its management. However, there are no recommendations for fatigue management in people with I-RMDs. This lack of guidance is challenging for those living with fatigue and health professionals delivering clinical care. Therefore, our aim was to develop EULAR recommendations for the management of fatigue in people with I-RMDs. METHODS: A multidisciplinary taskforce comprising 26 members from 14 European countries was convened, and two systematic reviews were conducted. The taskforce developed the recommendations based on the systematic review of evidence supplemented with taskforce members' experience of fatigue in I-RMDs. RESULTS: Four overarching principles (OAPs) and four recommendations were developed. OAPs include health professionals' awareness that fatigue encompasses multiple biological, psychological and social factors which should inform clinical care. Fatigue should be monitored and assessed, and people with I-RMDs should be offered management options. Recommendations include offering tailored physical activity and/or tailored psychoeducational interventions and/or, if clinically indicated, immunomodulatory treatment initiation or change. Patient-centred fatigue management should consider the individual's needs and preferences, their clinical disease activity, comorbidities and other psychosocial and contextual factors through shared decision-making. CONCLUSIONS: These 2023 EULAR recommendations provide consensus and up-to-date guidance on fatigue management in people with I-RMDs.
Microneedles in diagnostic, treatment and theranostics: An advancement in minimally-invasive delivery system.
Microneedle (MN) technology plays an important role in biomedical engineering for their less intrusive access to the skin due to minimally or painless penetration, enhancement of drug permeability, improvement of detectability of biomolecules in the epidermal and dermal layers with therapeutic efficacy and safety. Furthermore, MNs possess some major disadvantages like difficulty in scale-up technique, variation in drug delivery pattern with respect to external environment of skin, blockage of arrays due to dermal tissues, induction of inflammation or allergy at the site of administration and restriction of dosing range based on the size of active. Additionally, microneedle acts as a transdermal theranostic device for monitoring the physiological parameters in clinical studies. The investigation of drug transfer mechanisms through microneedles includes coat and poke, poke and flow, poke and patch and poke and release method. This review article discusses different categories of microneedles with fabrication methods such as photolithography, laser cutting, 3D printing, etc. in therapeutic applications for treating cancer, diabetes, arthritis, obesity, neurological disorders, and glaucoma. Biosensing devices based on microneedles may detect target analytes directly in the interstitial fluid by penetrating the stratum corneum of the skin and thus microneedles-based devices can be considered as a single tool in diagnostic sensing and therapeutic administration of drugs inside the body. Moreover, the clinical status and commercial availability of microneedle devices are discussed in this review article to offer new insights to researchers and scientists. Continuous monitoring particularly for the determination of blood glucose concentration is one of the most important requirements for the development of next-generation healthcare devices. The aim of this review article focuses mainly on the theranostic applications of microneedles in various medical conditions such as malaria, glaucoma, cancer, etc.
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
The immune-epithelial-stromal interactions underpinning intestinal damage in celiac disease (CD) are incompletely understood. To address this, we performed single-cell transcriptomics (RNA sequencing; 86,442 immune, parenchymal and epithelial cells; 35 participants) and spatial transcriptomics (20 participants) on CD intestinal biopsy samples. Here we show that in CD, epithelial populations shifted toward a progenitor state, with interferon-driven transcriptional responses, and perturbation of secretory and enteroendocrine populations. Mucosal T cells showed numeric and functional changes in regulatory and follicular helper-like CD4+ T cells, intraepithelial lymphocytes, CD8+ and γδ T cell subsets, with skewed T cell antigen receptor repertoires. Mucosal changes remained detectable despite treatment, representing a persistent immune-epithelial 'scar'. Spatial transcriptomics defined transcriptional niches beyond those captured in conventional histological scores, including CD-specific lymphoid aggregates containing T cell-B cell interactions. Receptor-ligand spatial analyses integrated with disease susceptibility gene expression defined networks of altered chemokine and morphogen signaling, and provide potential therapeutic targets for CD prevention and treatment.
Clinical and cost-effectiveness of a personalised guided consultation versus usual physiotherapy care in people presenting with shoulder pain: a protocol for the PANDA-S cluster randomised controlled trial and process evaluation.
INTRODUCTION: Musculoskeletal shoulder pain is a common reason for people to be treated in physiotherapy services, but diagnosis can be difficult and often does not guide treatment or predict outcome. People with shoulder pain cite a need for clear information, and timely, tailored consultations for their pain. This trial will evaluate the introduction of a personalised guided consultation to help physiotherapists manage care for individuals with shoulder pain. METHODS AND ANALYSIS: This is a cluster randomised controlled trial to evaluate the clinical and cost-effectiveness of introducing a personalised guided consultation compared with usual UK NHS physiotherapy care. Physiotherapy services (n=16) will be randomised in a 1:1 ratio to either intervention (physiotherapy training package and personalised guided consultation incorporating a new prognostic tool) or control (usual care); 832 participants (416 in each arm) identified from participating physiotherapy service waiting lists aged 18 years or over with shoulder pain will be enrolled. Follow-up will occur at 3 time points: 6 weeks, 6 months and 12 months. The primary outcome will be the Shoulder Pain and Disability Index (SPADI) score over 12 months. Secondary outcomes include global perceived change of the shoulder condition, sleep, work absence and the impact of shoulder pain on work performance, healthcare utilisation and health-related quality of life (using EuroQol 5 Dimension 5 Level (EQ-5D-5L)). A multimethod process evaluation will investigate views and experiences of participants and physiotherapists, assess uptake, facilitators and barriers to delivery, and changes in factors assumed to explain intervention outcomes. Primary analysis of effectiveness will be by intention-to-treat, and a health economic evaluation will assess cost-utility of introducing the personalised consultation. ETHICS AND DISSEMINATION: The trial received ethics approval from the Yorkshire & The Humber (South Yorkshire) Research Ethics Committee (REC reference: 23/YH/0070). Findings will be shared through journal publications, media outlets and conference presentations. Supported by patient contributors and clinical advisors, we will communicate findings through a designated website, networks, newsletters, leaflets and in the participating physiotherapy services. TRIAL REGISTRATION NUMBER: ISRCTN45377604.
Lifestyle Modifications and Nonpharmacologic Interventions to Improve Outcomes in Psoriatic Arthritis: A Systematic Review.
PURPOSE: Psoriatic arthritis (PsA) is a multisystem inflammatory disorder associated with significant mortality and morbidity, including functional impairment and psychological disability. Although evidence-based treatment recommendations are available for the use of drug treatments in PsA, there is little guidance for health professionals on nonpharmacologic and psychological interventions that may be useful in PsA. The objective of this systematic review (SR) was to identify how lifestyle modifications and the use of nonpharmacologic and psychological interventions may improve the outcomes of patients with PsA. METHODS: Studies were included if they evaluated adults diagnosed with PsA and included exposure to nonpharmacologic interventions, psychological interventions, and lifestyle modifications. The outcomes used needed to have been validated in PsA. A systematic literature search was run on May 28, 2021, in the Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), EMBASE, Global Health, MEDLINE, and PsycINFO databases to identify articles related to lifestyle modifications and nonpharmacologic or psychological interventions for adults with PsA published between 2010 and 2021. Two review authors independently screened and selected full-text studies for inclusion in the SR. Risk of bias was assessed with either the Risk of Bias 2 (ie, RoB 2) tool or Critical Appraisal Skills Program checklist depending on the study type. FINDINGS: The search strategy identified 26,132 references. Eight studies examining lifestyle modifications and the effect on PsA were eligible to be included in the SR. Three of the 8 studies were randomized controlled trials, and 5 were nonrandomized studies. Three studies assessed physical activity, 3 assessed diet, 1 study assessed smoking, and another study assessed mud bath therapy. There was large heterogeneity between studies, and the measures of disease activity, and psychological and functional outcomes varied widely between studies. IMPLICATIONS: Although this SR identified 8 relevant studies, these studies did not provide high-quality evidence to guide patients for non-drug treatments of PsA. The effectiveness of these interventions has therefore not been established. We found that physical activity seems to have a positive impact on disease activity and psychological well-being. Further well-designed research studies are needed to develop treatment recommendations. PROSPERO identifier: CRD42021257404.
Relational spirals and thriving: A longitudinal investigation of older workers
Thriving is believed to occur when employees feel a sense of progress and momentum in the organization. This conceptual basis for thriving is inherently temporal—implying an underlying individual change process—which sets thriving apart from other well-being criteria in the Human Resource Management literature. However, surprisingly little research has demonstrated and unpacked the change and development processes that lead to thriving. In this article, we develop and test a theoretical model of the dynamic origins of thriving in a socially important context: the aging workforce. Specifically, we propose that older workers thrive when they experience relational spirals: a deepening of the employee-organization relationship as psychological contracts and role expansion drive each other in a mutually reinforcing spiral. Results from a large-scale nationally representative longitudinal study of 3370 Australian older workers—spanning 1.5 years and three time points—support the proposed model. Older workers' relational psychological contracts and role expansion formed a mutually reinforcing spiral process over time which ultimately led to higher levels of thriving. These results held even after imposing autoregressive control of lagged variables at earlier time points, and after accounting for the contributions of transactional psychological contracts to the spiral process. Our theorizing and empirical approach brings dynamic processes to the forefront of HR research on thriving, and points to implications for the role of HR in successful aging.
Leaders laughing in the line of fire: An emotional aperture perspective on leader laughter in response to critical questions.
Leaders are frequently put in the difficult position of repudiating critical questions in front of their followers. To help manage this situation, leaders sometimes express laughter in the hopes that it will "lubricate" their interaction and reduce perceptions that they are aggressive or confrontational with the critical questioner. Ironically, leaders' laughter may backfire by diminishing their apparent friendliness and approachability in the eyes of the witnessing followers. In this article, we employ an emotional aperture perspective to examine two seemingly contradictory theoretical perspectives regarding the potential impact of laughter on the witnessing followers' perception of a leader's warmth and effectiveness. Findings from nine studies across 2,012 adults show that leader laughter-even expressed briefly-bolsters or damages leader effectiveness depending on one important contingency: whether the leader's laughter is shared by the questioner. Unshared laughter reduces leader effectiveness by undermining leaders' apparent warmth, while shared laughter increases leader effectiveness by enhancing leaders' apparent warmth. We discuss implications for the literature on emotion expression, leadership events, and leader perception and influence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Efficacy of pharmacological interventions: a systematic review informing the 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.
OBJECTIVE: To identify the best evidence on the efficacy of pharmacological interventions in reducing fatigue in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and to summarise their safety in the identified studies to inform European Alliance of Associations for Rheumatology recommendations for the management of fatigue in people with I-RMDs. METHODS: Systematic review of adults with I-RMDs conducted according to the Cochrane Handbook. Search strategy ran in Medline, Embase, Cochrane Library, CINAHL Complete, PEDro, OTseeker and PsycINFO. Only randomised controlled trials (RCTs) or controlled clinical trials were eligible. Assessment of risk of bias, data extraction and synthesis performed by two reviewers independently and in duplicate. Data pooled in statistical meta-analyses. RESULTS: From 4151 records, 455 were selected for full-text review, 99 fulfilled the inclusion criteria and 19 RCTs were included in meta-analyses. Adalimumab was superior to placebo in reducing fatigue at 12 and 52 weeks in rheumatoid arthritis (RA) (n=3 and 2 RCTs; mean difference (MD)= -3.03, p<0.001; MD=-2.25, p=0.03, respectively). Golimumab (n=2 RCTs; 24 weeks: MD=-5.27, p<0.001), baricitinib (n=2 RCTs; 24 weeks: MD=-4.06, p<0.001), sarilumab (n=2 RCTs; 24 weeks: MD=-3.15, p<0.001), tocilizumab (n=3 RCTs; 24 weeks: MD=-3.69, p<0.001) and tofacitinib (n=3 RCTs; 12 weeks: MD=-4.44, p<0.001) were also superior to placebo in reducing fatigue in RA. A dose/effect relationship was observed for sarilumab, tocilizumab and tofacitinib. In spondyloarthritis (excluding psoriatic arthritis), secukinumab was superior to placebo in reducing fatigue at 16 weeks (n=2 RCTs; MD=-4.15, p<0.001), with a dose/effect relationship also observed. The narrative results of the RCTs not included in the meta-analysis indicated that several other pharmacological interventions were efficacious in reducing fatigue, with reassuring safety results. CONCLUSIONS: Several pharmacological interventions are efficacious and generally safe for managing fatigue in people with I-RMDs.
Efficacy of non-pharmacological interventions: a systematic review informing the 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.
OBJECTIVE: To identify the best evidence on the efficacy of non-pharmacological interventions in reducing fatigue in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and to summarise their safety in the identified studies to inform European Alliance of Associations for Rheumatology recommendations for the management of fatigue in people with I-RMDs. METHODS: Systematic review of randomised controlled trials (RCTs) including adults with I-RMDs conducted according to the Cochrane Handbook. Search strategy ran in Medline, Embase, Cochrane Library, CINAHL Complete, PEDro, OTseeker and PsycINFO. Assessment of risk of bias, data extraction and synthesis were performed by two reviewers independently. Data were pooled in meta-analyses. RESULTS: From a total of 4150 records, 454 were selected for full-text review, 82 fulfilled the inclusion criteria and 55 RCTs were included in meta-analyses. Physical activity or exercise was efficacious in reducing fatigue in rheumatoid arthritis (RA) (standardised mean differences (SMD)=-0.23, 95% CI=-0.37 to -0.1), systemic lupus erythematosus (SLE) (SMD=-0.54, 95% CI=-1.07 to -0.01) and spondyloarthritis (SMD=-0.94, 95% CI=-1.23 to -0.66); reduction of fatigue was not significant in Sjögren's syndrome (SMD=-0.83, 95% CI=-2.13 to 0.47) and systemic sclerosis (SMD=-0.66, 95% CI=-1.33 to 0.02). Psychoeducational interventions were efficacious in reducing fatigue in RA (SMD=-0.32, 95% CI=-0.48 to -0.16), but not in SLE (SMD=-0.19, 95% CI=-0.46 to 0.09). Follow-up models in consultations (SMD=-0.05, 95% CI=-0.29 to 0.20) and multicomponent interventions (SMD=-0.20, 95% CI=-0.53 to 0.14) did not show significant reductions of fatigue in RA. The results of RCTs not included in the meta-analysis suggest that several other non-pharmacological interventions may provide a reduction of fatigue, with reassuring safety results. CONCLUSIONS: Physica activity or exercise and psychoeducational interventions are efficacious and safe for managing fatigue in people with I-RMDs.
The role of physical activity in obesity: let's actively manage obesity.
Obesity, physical inactivity and sedentary behaviour are major public health concerns. A complex interaction of many factors leads to obesity, which requires an individualised multicomponent management strategy. As new interventions become available to help individuals manage obesity, it is essential that physical activity remains a core part of the approach. Here, we summarise current evidence regarding the benefits of physical activity as part of a management strategy of obesity. Additionally, we discuss current methods for increasing physical activity levels in individuals with obesity and outline the role of sport and exercise medicine physicians as part of the multidisciplinary team.
The role of physical activity in obesity: let's actively manage obesity.
Obesity, physical inactivity and sedentary behaviour are major public health concerns. A complex interaction of many factors leads to obesity, which requires an individualised multicomponent management strategy. As new interventions become available to help individuals manage obesity, it is essential that physical activity remains a core part of the approach. Here, we summarise current evidence regarding the benefits of physical activity as part of a management strategy of obesity. Additionally, we discuss current methods for increasing physical activity levels in individuals with obesity and outline the role of sport and exercise medicine physicians as part of the multidisciplinary team.
What Makes a Creative Team Player? A Social Dilemma Perspective on External Regulation and Creativity
Creativity is important for a group’s success, and thus, groups often demand that their members contribute creativity by setting up group goals. Group goal external regulation arises when individual members feel that their behavior is externally initiated and enforced. While research from the self-determination perspective suggests that such external regulation undermines creativity, emerging research also suggests the opposite: external regulation has motivational functions boosting creativity. To integrate these seemingly contradictory perspectives, we developed a contingency model (based on social dilemma theory) to explain the impacts of group goal external regulation. Specifically, conceiving creativity in the individual-group context of multiple goals, we suggest that group goal external regulation can prompt or hinder individual member creativity, depending on their individual goal progress (“concern for me”) and group identification (“concern for us”). We found support from two studies that when group identification is high, individuals demonstrate higher levels of creativity, irrespective of their individual goal progress and group goal external regulation experienced. When group identification is low, individuals demonstrate more contingent responses—that is, external regulation is positively (negatively) related to individual member creativity when their individual goal progress is poor (good).
Potential of nanocarriers using ABC transporters for antimicrobial resistance.
Some existing therapies such as antimicrobial regimens, drug combinations, among others, are employed for the treatment of infections that are a threat to the healthcare industry owing to low drug efficacy, increasing dosage regimes, mutation in bacteria and poor pharmacokinetics/pharmacodynamics properties of drugs. Overuse of antibiotics is fostering the emergence and spread of inherent microorganisms that confer temporary and permanent resistance. Nanocarriers accompanying the ABC transporter efflux mechanism are considered 'magic bullets' (i.e., effective antibacterial agents) and can traverse the multidrug-resistant obstacle owing to their multifunctional capabilities (e.g., nanostructure, variability in in vivo functions, etc.) by interfering with normal cell activity. This review focuses on novel applications of the ABC transporter pump by nanocarriers to overcome the resistance caused by the various organs of the body.
Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study.
PURPOSE: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. METHODS: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. RESULTS: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8-4.6) in CFS 4 vs 1-3; OR 12.4 (6.2-24.5) in CFS 8 vs 1-3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3-1.9) in CFS 4 compared to 0.2 (0.1-0.7) in CFS 8). These risks were both independent of age and dementia. CONCLUSION: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes.