Implementing good life with osteoArthritis from Denmark (GLA:D®) in australian public hospitals. Part 1: Feasibility.

Background: Literature reporting positive outcomes from the Good Life with osteoArthritis in Denmark (GLA:D®) program in Australia mainly involves patients attending private physiotherapy services.

Objective: Evaluate the feasibility of implementing GLA:D® in Australian public hospitals.

Design: Implementation study in three metropolitan tertiary public hospitals over six months.

Prospective validity of a clinical prediction rule for response to non-surgical multidisciplinary management of knee osteoarthritis in tertiary care: a multisite prospective longitudinal study.

Objectives: We tested a previously developed clinical prediction tool-a nomogram consisting of four patient measures (lower patient-expected benefit, lower patient-reported knee function, greater knee varus angle and severe medial knee radiological degeneration) that were related to poor response to non-surgical management of knee osteoarthritis. This study sought to prospectively evaluate the predictive validity of this nomogram to identify patients most likely to respond poorly to non-surgical management of knee osteoarthritis.

Design: Multisite prospective longitudinal study.

Response to letter to editor: The association between hip strength, physical function and dynamic balance in people with unilateral knee osteoarthritis: A cross-sectional study.

We thank the reader for their interest and response to our study investigating the association between clinical measures of hip strength in multiple directions and physical function (including dynamic balance) in people with knee osteoarthritis. Below, we provide a response to their questions, in turn.

The association between hip strength, physical function and dynamic balance in people with unilateral knee osteoarthritis: A cross-sectional study.

Background: In people with knee osteoarthritis, the association between multidirectional hip strength and physical function or balance is unknown.

Objective: To determine the relationship between hip flexion, extension, abduction, adduction, external and internal rotation strength and (1) physical function and (2) dynamic balance.

Design: Cross-sectional.

Hip strength, quadriceps strength and dynamic balance are lower in people with unilateral knee osteoarthritis compared to their non-affected limb and asymptomatic controls.

Background: There is insufficient literature on multi-directional hip strength differences and dynamic balance between people with knee osteoarthritis (KOA) and healthy controls.

Objective: In people with unilateral KOA, determine if hip/knee strength and dynamic balance differs (i) between sides, and (ii) compared to controls.

Methods: Thirty-six participants (17 women; 65.

Patient characteristics associated with a poor response to non-surgical multidisciplinary management of knee osteoarthritis: a multisite prospective longitudinal study in an advanced practice physiotherapist-led tertiary service.

Objectives: To explore patient characteristics recorded at the initial consultation associated with a poor response to non-surgical multidisciplinary management of knee osteoarthritis (KOA) in tertiary care.

Design: Prospective multisite longitudinal study.

Setting: Advanced practice physiotherapist-led multidisciplinary orthopaedic service within eight tertiary hospitals.

Does adding hip exercises to quadriceps exercises result in superior outcomes in pain, function and quality of life for people with knee osteoarthritis? A systematic review and meta-analysis.

Objectives: To determine, in people with knee osteoarthritis (KOA): i) the effectiveness of adding hip strengthening exercises to quadriceps exercises and ii) the type of hip strengthening exercise with the greatest evidence for improving pain, function and quality of life.

Design: Systematic review with meta-analysis.

Data Sources: Medline, Embase, Cochrane, CINAHL and SportDiscus databases were searched from inception to January 2018.

Proteome-wide analysis of CD8+ T cell responses to EBV reveals differences between primary and persistent infection.

Human herpesviruses are antigenically rich agents that induce strong CD8+T cell responses in primary infection yet persist for life, continually challenging T cell memory through recurrent lytic replication and potentially influencing the spectrum of antigen-specific responses. Here we describe the first lytic proteome-wide analysis of CD8+ T cell responses to a gamma1-herpesvirus, Epstein-Barr virus (EBV), and the first such proteome-wide analysis of primary versus memory CD8+ T cell responses to any human herpesvirus. Primary effector preparations were generated directly from activated CD8+ T cells in the blood of infectious mononucleosis (IM) patients by in vitro mitogenic expansion.

Asymptomatic Primary Infection with Epstein-Barr Virus: Observations on Young Adult Cases.

Epstein-Barr virus (EBV) is typically acquired asymptomatically in childhood. In contrast, infection later in life often leads to infectious mononucleosis (IM), a febrile illness characterized by anti-EBV IgM antibody positivity, high loads of circulating latently infected B cells, and a marked lymphocytosis caused by hyperexpansion of EBV-specific CD8 T cells plus a milder expansion of CD56 NKG2A KIR natural killer (NK) cells. How the two situations compare is unclear due to the paucity of studies on clinically silent infection.

Inherited CD70 deficiency in humans reveals a critical role for the CD70-CD27 pathway in immunity to Epstein-Barr virus infection.

Epstein-Barr virus (EBV) infection in humans is a major trigger of malignant and nonmalignant B cell proliferations. CD27 is a co-stimulatory molecule of T cells, and inherited CD27 deficiency is characterized by high susceptibility to EBV infection, though the underlying pathological mechanisms have not yet been identified. In this study, we report a patient suffering from recurrent EBV-induced B cell proliferations including Hodgkin's lymphoma because of a deficiency in CD70, the ligand of CD27.

Azidothymidine Sensitizes Primary Effusion Lymphoma Cells to Kaposi Sarcoma-Associated Herpesvirus-Specific CD4+ T Cell Control and Inhibits vIRF3 Function.

Kaposi sarcoma-associated herpesvirus (KSHV) is linked with the development of Kaposi sarcoma and the B lymphocyte disorders primary effusion lymphoma (PEL) and multi-centric Castleman disease. T cell immunity limits KSHV infection and disease, however the virus employs multiple mechanisms to inhibit efficient control by these effectors. Thus KSHV-specific CD4+ T cells poorly recognize most PEL cells and even where they can, they are unable to kill them.

Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs.

Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs.

Primary B Lymphocytes Infected with Kaposi's Sarcoma-Associated Herpesvirus Can Be Expanded In Vitro and Are Recognized by LANA-Specific CD4+ T Cells.

Unlabelled: Kaposi's sarcoma-associated herpesvirus (KSHV) has tropism for B lymphocytes, in which it establishes latency, and can also cause lymphoproliferative disorders of these cells manifesting as primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). T cell immunity is vital for the control of KSHV infection and disease; however, few models of B lymphocyte infection exist to study immune recognition of such cells. Here, we developed a model of B lymphocyte infection with KSHV in which infected tonsillar B lymphocytes were expanded by providing mitogenic stimuli and then challenged with KSHV-specific CD4(+)T cells.

T-Cell Responses to EBV.

Epstein-Barr virus (EBV) is arguably one of the most successful pathogens of humans, persistently infecting over ninety percent of the world's population. Despite this high frequency of carriage, the virus causes apparently few adverse effects in the vast majority of infected individuals. Nevertheless, the potent growth transforming ability of EBV means the virus has the potential to cause malignancies in infected individuals.

Early virological and immunological events in Epstein-Barr virus infection.

Epstein-Barr virus (EBV) is a γ-herpesvirus which establishes a chronic yet asymptomatic infection in humans. This saliva transmitted virus has a tropism for B lymphocytes, in which it establishes a latent infection, and epithelial cells where the virus replicates to produce infectious particles. Although the majority of infections are apparently benign, primary EBV infection can be associated with an acute febrile syndrome, infectious mononucleosis, while infection is also associated with the development of malignancies of B lymphocyte and epithelial origin.

Impaired Epstein-Barr Virus-Specific Neutralizing Antibody Response during Acute Infectious Mononucleosis Is Coincident with Global B-Cell Dysfunction.

Here we present evidence for previously unappreciated B-cell immune dysregulation during acute Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). Longitudinal analyses revealed that patients with acute IM have undetectable EBV-specific neutralizing antibodies and gp350-specific B-cell responses, which were associated with a significant reduction in memory B cells and no evidence of circulating antibody-secreting cells. These observations correlate with dysregulation of tumor necrosis factor family members BAFF and APRIL and increased expression of FAS on circulating B cells.

Cytokine-Mediated Loss of Blood Dendritic Cells During Epstein-Barr Virus-Associated Acute Infectious Mononucleosis: Implication for Immune Dysregulation.

Acute infectious mononucleosis (IM) is associated with altered expression of inflammatory cytokines and disturbed T-cell homeostasis, however, the precise mechanism of this immune dysregulation remains unresolved. In the current study we demonstrated a significant loss of circulating myeloid and plasmacytoid dendritic cells (DCs) during acute IM, a loss correlated with the severity of clinical symptoms. In vitro exposure of blood DCs to acute IM plasma resulted in loss of plasmacytoid DCs, and further studies with individual cytokines showed that exposure to interleukin 10 could replicate this effect.

Activation of DNA Damage Response Pathways during Lytic Replication of KSHV.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of several human malignancies. Human tumour viruses such as KSHV are known to interact with the DNA damage response (DDR), the molecular pathways that recognise and repair lesions in cellular DNA. Here it is demonstrated that lytic reactivation of KSHV leads to activation of the ATM and DNA-PK DDR kinases resulting in phosphorylation of multiple downstream substrates.

Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children.

Epstein-Barr virus (EBV) infection often occurs in early childhood and is asymptomatic. However, if delayed until adolescence, primary infection may manifest as acute infectious mononucleosis (AIM), a febrile illness characterised by global CD8+ T-cell lymphocytosis, much of it reflecting a huge expansion of activated EBV-specific CD8+ T-cells. While the events of AIM have been intensely studied, little is known about how these relate to asymptomatic primary infection.

The immunology of Epstein-Barr virus-induced disease.

Epstein-Barr virus (EBV) is usually acquired silently early in life and carried thereafter as an asymptomatic infection of the B lymphoid system. However, many circumstances disturb the delicate EBV-host balance and cause the virus to display its pathogenic potential. Thus, primary infection in adolescence can manifest as infectious mononucleosis (IM), as a fatal illness that magnifies the immunopathology of IM in boys with the X-linked lymphoproliferative disease trait, and as a chronic active disease leading to life-threatening hemophagocytosis in rare cases of T or natural killer (NK) cell infection.

Cooperation between Epstein-Barr virus immune evasion proteins spreads protection from CD8+ T cell recognition across all three phases of the lytic cycle.

CD8+ T cell responses to Epstein-Barr virus (EBV) lytic cycle expressed antigens display a hierarchy of immunodominance, in which responses to epitopes of immediate-early (IE) and some early (E) antigens are more frequently observed than responses to epitopes of late (L) expressed antigens. It has been proposed that this hierarchy, which correlates with the phase-specific efficiency of antigen presentation, may be due to the influence of viral immune-evasion genes. At least three EBV-encoded genes, BNLF2a, BGLF5 and BILF1, have the potential to inhibit processing and presentation of CD8+ T cell epitopes.

A mutation in X-linked inhibitor of apoptosis (G466X) leads to memory inflation of Epstein-Barr virus-specific T cells.

Mutations in the X-linked inhibitor of apoptosis (XIAP) gene have been associated with XLP-like disease, including recurrent Epstein-Barr virus (EBV)-related haemophagocytic lymphohystiocytosis (HLH), but the immunopathogenic bases of EBV-related disease in XIAP deficiency is unknown. We present the first analysis of EBV-specific T cell responses in functional XIAP deficiency. In a family of patients with a novel mutation in XIAP (G466X) leading to a late-truncated protein and varying clinical features, we identified gradual hypogammaglobulinaemia and large expansions of T cell subsets, including a prominent CD4(+) CD8(+) population.

Cellular immune controls over Epstein-Barr virus infection: new lessons from the clinic and the laboratory.

Epstein-Barr virus (EBV), a human herpesvirus with potent B cell growth transforming ability, induces multiple cellular immune responses in the infected host. How these host responses work together to prevent virus pathogenicity, and how immune imbalance predisposes to disease, remain poorly understood. Here, we describe three ongoing lines of enquiry that are shedding new light on these issues.

Early lung development: lifelong effect on respiratory health and disease.

Interest in the contribution of changes in lung development during early life to subsequent respiratory morbidity is increasing. Most evidence of an association between adverse intrauterine factors and structural effects on the developing lung is from animal studies. Such evidence has been augmented by epidemiological studies showing associations between insults to the developing lung during prenatal and early postnatal life and adult respiratory morbidity or reduced lung function, and by physiological studies that have elucidated mechanisms underlying these associations.

IRF-4-mediated CIITA transcription is blocked by KSHV encoded LANA to inhibit MHC II presentation.

Peptides presentation to T cells by MHC class II molecules is of importance in initiation of immune response to a pathogen. The level of MHC II expression directly influences T lymphocyte activation and is often targeted by various viruses. Kaposi's sarcoma-associated herpesvirus (KSHV) encoded LANA is known to evade MHC class I peptide processing, however, the effect of LANA on MHC class II remains unclear.