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Background The transport and logistics industry contributes to a significant proportion of the Australian economy. However, few studies have explored the economic and clinical burden attributed to poor truck driver health. We therefore estimated the work-related mortality burden among truck drivers over a 10-year period. Methods Dynamic life table modelling was used to simulate the follow-up of the Australian male working-age population (aged 15–65 years) over a 10-year period of follow-up (2021–2030). The model estimated the number of deaths occurring among the Australian working population, as well as deaths occurring for male truck drivers. Data from the Driving Health study and other published sources were used to inform work-related mortality and associated productivity loss, hospitalisations and medication costs, patient utilities and the value of statistical life year (VoSLY). All outcomes were discounted by 5% per annum. Results Over 10 years, poor truck driver health was associated with a loss of 21,173 years of life lived (discounted), or 18,294 QALYs (discounted). Healthcare costs amounted to AU$485 million (discounted) over this period. From a broader, societal perspective, a total cost of AU$2.6 billion (discounted) in lost productivity and AU$4.7 billion in lost years of life was estimated over a 10-year period. Scenario analyses supported the robustness of our findings. Conclusions The health and economic consequences of poor driver health are significant, and highlight the need for interventions to reduce the burden of work-related injury or disease for truck drivers and other transport workers.

ObjectiveTo determine the continuity of care (CoC) provided by general practitioners among workers with low back pain; identify personal, workplace and social factors associated with CoC in this population; and investigate if CoC is associated with working time loss.Data sourcesAn administrative database containing accepted workers’ compensation claim and service level data, for workers with back pain from five Australian jurisdictions, injured between July 2010 and June 2015.Study DesignA retrospective cohort study. Outcomes were CoC with a general practitioner, measured with the Usual Provider Continuity index, and working time loss, measured as the number of weeks for which workers’ compensation income support benefits were paid.Extraction methodsEligible workers had at least four general practitioner services, and greater than two weeks working time loss. Usual Provider Continuity index score was categorised as complete, high, moderate, or low CoC. Ordinal logistic regression models examined factors associated with Usual Provider Continuity category. Quantile regression models examined association between duration of working time loss and Usual Provider Continuity category, in four groups with different volumes of general practitioner services.Principal FindingsComplete CoC was observed in 33.8% of workers, high CoC among 37.7%, moderate CoC in 22.1%, and low CoC in 6.4%. Higher Usual Provider Continuity was associated with fewer general practitioner services, older age, living in urban areas, an occupation as a Community and Personal Service Worker or Clerical and Administrative Worker, and the state of Victoria. In workers with more than two months of time loss, those with complete CoC consistently had shorter durations of time loss.ConclusionsHigher CoC with a general practitioner is associated with less working time loss and this relationship is strongest in the sub-acute phase of low back pain.Callout BoxWhat is known on this topicContinuity of care is a key component of best practice primary careLow back pain is a condition that often requires ongoing management and care from a general practitionerThe relationship between continuity of care and work disability duration, recovery and return to work in workers with low back pain is not knownWhat this study addsWorkers with low back pain who see the same general practitioner for all services (i.e., have a greater continuity of care) generally have shorter durations of working time lossHigher continuity of care was observed in workers who had fewer PCP services, were aged over 45, lived in urban areas, and worked as a Community and Personal Service Worker or Clerical and Administrative WorkerWorkers’ compensation systems should consider policies and guidelines that increase continuity of care in injured workers

Imaging mass cytometry (IMC) affords simultaneous immune-labelling/imaging of multiple antigens in the same tissue. Methods utilizing multiplex data beyond co-registration are lacking. This study developed and applied an innovative spatial analysis workflow for multiplex imaging data to IMC data determined from cardiac tissues and revealed the mechanism(s) of neutrophil-mediated post-myocardial-infarction damage.IMC produced multiplex images with various redox/inflammatory markers. The cardiac peri-infarct zone (PIZ) was determined to be up to 240 µm from the infarct border based on the presence of neutrophils. The tissue region beyond the infarct was defined as the remote area (RA). ImageJ was used to quantify the immunoreactivity. Functional assessments included infarct size, cell necro/apoptosis, total thiol assay and echocardiogram.Expression of damage markers decreased in order from the infarct area to PIZ and then RA, reflecting the neutrophil density in the regions. Concentrically spaced "shoreline contour analysis" around the cardiac infarct extending into the PIZ showed that immunoreactivity for damage markers decreased linearly with increasing distance from the infarct, concomitant with a decreasing neutrophil-myeloperoxidase (MPO) gradient from the infarct to the PIZ. Stratifying by concentric bands around individual MPOThis image-based quantitative protocol revealed the spatial association and provided potential molecular pathways responsible for neutrophil-mediated damage post-infarction.

Background: Fatigued driving is one of the leading factors contributing to road crashes in the trucking industry. The nature of trucking, prolonged working time, and irregular sleep patterns can negatively impact drivers’ health and wellbeing. However, there is limited research in Australia investigating the impact of demographic, occupational, or lifestyle factors on fatigue among truck drivers. Objective: This cross-sectional study examines the role of demographic, occupational, lifestyle, and other health risk factors associated with fatigue among Australian truck drivers. Method: This study was part of a larger study that used a short online survey with a follow-up telephone survey to capture in-depth information on a wide range of determinants related to truck drivers’ physical and mental health outcomes. Fatigue was measured by three questions, including the frequency of fatigue, fatigue management training, and strategies used to combat fatigue. Multivariate regression analysis was used to determine the specific impact of demographics, occupational factors, lifestyle factors, and other health risk factors on fatigue. Results: In total, 332 drivers completed both the online and telephone surveys; 97% were male, representing drivers from broad age groups and professional experience. The odds of being in the high-risk fatigue group were nearly three times higher in drivers who worked 40–60 h compared to those who worked < 40 h. Poor sleep increased the odds of high-risk fatigue by seventimes (95% CI: 2.26–21.67, p = 0.001). Drivers who reported experiencing loneliness also had double the odds of being at high risk of fatigued driving. Conclusions: The increased risk of fatigue in truck drivers is associated with prolonged working hours, poor sleep, and social aspects such as loneliness. Further interventions seeking to reduce driver fatigue should consider the impact of work schedules, the availability of quality sleeping spaces, and the level of social connections.

Background Following pandemic-related work loss, some people could return to work as restrictions eased, whilst localised lockdowns resulted in further loss of work. The long-term health effects of work loss within the pandemic remain unexplored, in addition to whether any health effects are persistent upon returning to work. Methods A prospective longitudinal cohort study of 2603 Australians monitored changes in health and work across four surveys during March-December 2020. Outcomes described psychological distress, and mental and physical health. Linear mixed regression models examined associations between changes in health and experiences of work loss, and return to work, over time. Results Losing work during the early pandemic stages was associated with long-term poorer mental health, which began to recover over time. Physical health deteriorated over time, greater for people not working at baseline. Being out of work was associated with poorer mental health, but better physical health. These effects were larger for people that had recently lost work than for people with sustained work loss, and retaining employment played a protective role. Conclusions Work cessation during the pandemic led to poor health outcomes and had long-lasting effects. Returning to work benefits mental health but may reduce physical activity in the short-term. We encourage the provision of accessible mental health supports immediately following loss of work, and for people with prolonged work loss. Key messages Remaining employed whilst not working partly ameliorates negative mental health impacts. Those experiencing persistent work loss, and the newly out-of-work, are most vulnerable to ill mental health.

Background In response to the second wave of COVID-19 in Australia a 4 month community-wide lockdown resulted in Victoria, Australia. We explored the health impacts during lockdown and following its conclusion. Methods A cohort of 898 working-age Australians enrolled in a national longitudinal cohort study, completing surveys prior to, during, and following a Victorian lockdown during the southern hemisphere winter and early spring 2020. Mixed linear regression models examined health outcomes during and following the lockdown. Generalised estimating equations assessed changes in several determinants of health such as social interactions, engagement in work and finances. Results The Victorian lockdown had negative consequences for mental health and increased levels of psychological distress. These health impacts coincided with greater social isolation and cessation of work. Following the conclusion of lockdown, outcomes assessing mental health, work and social interactions had recovered to an extent whereby no significant long-lasting effects were identified compared to pre-lockdown conditions. Conclusions Extended community lockdowns have adverse health consequences. Governments should weigh the potential health impacts of lockdown with the benefits of reducing COVID-19 transmission. Services and programs to reduce the negative impacts of lockdown may include increases in mental health care, encouraging safe social interactions and financial support to maintain employment relationships. Longer-term follow-up is required to identify any persistent health effects of community lockdowns. Key messages Lockdowns result in adverse health consequences, and some quickly recover. Timely services and programs are encouraged to reduce negative impacts of lockdowns such as mental health supports and promoting safe interactions.

Objectives To determine health impacts during, and following, an extended community lockdown and COVID-19 outbreak in the Australian state of Victoria, compared with the rest of Australia. Methods A national cohort of 898 working-age Australians enrolled in a longitudinal cohort study, completing surveys before, during, and after a 112-day community lockdown in Victoria (8 July– 27 October 2020). Outcomes included psychological distress, mental and physical health, work, social interactions and finances. Regression models examined health changes during and following lockdown. Results The Victorian lockdown led to increased psychological distress. Health impacts coincided with greater social isolation and work loss. Following the extended lockdown, mental health, work and social interactions recovered to an extent whereby no significant long-lasting effects were identified in Victoria compared to the rest of Australia. Conclusion The Victorian community lockdown had adverse health consequences, which reversed upon release from lockdown. Governments should weigh all potential health impacts of lockdown. Services and programs to reduce the negative impacts of lockdown may include increases in mental health care, encouraging safe social interactions and supports to maintain employment relationships.

PurposeTo determine the nature and prevalence of workers’ concerns regarding workplaces reopening during the pandemic. To identify characteristics of workers and industries where particular concerns are more common.MethodsProspective cohort study of 1063 employed Australian adults, enrolled at the start of the pandemic. Data on attitudes to workplaces reopening were collected 1 July – 30 September 2020. The frequency of concerns describes infection risk and changes to work and impact on home life. Regression models examined associations between demographic and industry factors with reopening concerns.ResultsMore than four in five (82.4%) of workers reported concerns about workplace infection risk. Just over half (53.4%) reported concerns about impacts to work and home life. Concerns were more prevalent for workers reporting psychological distress, financial stress, and among those exclusively working from home. Concerns regarding infection risk were common for workers in health care (IRR=1.16, 95% CI=[1.01, 1.33]), retail (IRR=1.31, 95% CI=[1.06, 1.61]), and accommodation/food service industries (IRR=1.25, 95% CI=[1.01, 1.55]). Concerns regarding changes to work and home life were more common for female workers (IRR=1.24, 95% CI=[1.07, 1.43]), and partners/spouses with dependent children (IRR=1.44, 95% CI=[1.16, 1.79]).ConclusionConcerns of COVID-19 infection in the workplace are common. Many workers are also concerned about changes to their work and home life. The prevalence of concerns is related to the nature of work and responsibilities at home. Actions that reduce risk of workplace transmission, coupled with effective communication of infection controls, may alleviate worker concerns whilst recognising workers’ family and social circumstances.

Background Engagement in work is an important determinant of health. In response to the COVID-19 pandemic, public health measures imposed to reduce viral transmission resulted in large-scale loss of work during the early stages of the pandemic, contributing to declined mental and physical health. As the pandemic unfolded, the Australian economy began to recover and some people could return to work, whilst localised lockdowns resulted in further loss of work for others. The long-term health effects of work loss remain unexplored within the COVID-19 pandemic context, in addition to whether any health effects are persistent upon returning to work. Methods A prospective longitudinal cohort study of 2603 participants across Australia monitored changes in health and work between March and December 2020, with participants completing surveys at baseline and 1, 3 and 6 months later. Outcomes described psychological distress, and mental and physical health. Linear mixed regression models examined associations between changes in health and experiences of work loss, and return to work, over time. Results Losing work during the early stages of the pandemic was associated with long-term poorer mental health, which began to recover over time as some returned to work. Physical health deteriorated over time, greater for people not working at baseline. Being out of work was associated with poorer mental health, but better physical health. These effects were larger for people that had recently lost work than for people with sustained work loss, and retaining employment played a protective role. Generally, returning to work resulted in poorer physical health and improvements in mental health, although this depended on the broader context of changes in work. Conclusions Work cessation during the pandemic led to poor health outcomes and had long-lasting effects. Returning to work benefits mental health but may reduce physical activity in the short-term. We encourage the provision of accessible mental health supports and services immediately following loss of work, and for people with prolonged forms of work loss. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12620000857909.

Purpose To determine if losing work during the COVID-19 pandemic is associated with mental and physical health status. To determine if social interactions and financial resources moderate the relationship between work loss and health. Methods Participants were Australians aged 18 + years that were employed in paid work prior to the COVID-19 pandemic who responded to an online or telephone survey from 27th March to 12th June 2020 as part of a prospective longitudinal cohort study. Outcome measures include Kessler-6 score > 18 indicating high psychological distress, and Short Form 12 (SF-12) mental health or physical health component score

ObjectiveTo determine if losing work during the COVID-19 pandemic is associated with mental and physical health. To determine if social interactions and financial resources moderate the relationship between work loss and health.DesignBaseline data from a prospective longitudinal cohort study.SettingAustralia, 27th March to 12th June 2020.ParticipantsAustralians aged 18+ years, employed in a paid job prior to the COVID-19 pandemic who responded to an online or telephone survey.Main Outcome MeasuresKessler-6 score > 18 indicating high psychological distress. Short Form 12 (SF-12) mental health or physical health component score < = 45 indicating poor mental or physical health.Results2,603 respondents including groups who had lost their job (N = 541), were not working but remained employed (N = 613), were working less (N = 789) and whose work was unaffected (N = 789). Three groups experiencing work loss had greater odds of high psychological distress (AOR = 2.22–3.66), poor mental (AOR = 1.78–2.27) and physical health (AOR = 2.10–2.12) than the unaffected work group. Poor mental health was more common than poor physical health. The odds of high psychological distress (AOR = 5.43–8.36), poor mental (AOR = 1.92–4.53) and physical health (AOR = 1.93–3.90) were increased in those reporting fewer social interactions or less financial resources.ConclusionLosing work during the COVID-19 pandemic is associated with mental and physical health problems, and this relationship is moderated by social interactions and financial resources. Responses that increase financial security and enhance social connections may partially alleviate the health impacts of work loss.RegistrationAustralian New Zealand Clinical Trials Registry: ACTRN12620000857909.

IntroductionThis study estimated the extent of psychological distress among people losing work during the coronavirus disease of 2019 (COVID-19) pandemic in Australia, and examined associations between distress, nature of work loss and degree of social interaction.MethodsData were from a baseline online survey of an inception cohort recruited in the weeks following the introduction of physical distancing and movement restrictions to contain the spread of COVID-19 in Australia. These restrictions resulted in widespread unemployment and working hour reduction. Psychological distress was measured using the Kessler-6 scale. Data on nature of work loss, social interactions, demographic, job and occupational characteristics were also collected. Regression modelling was conducted to determine the relationship between work loss, social interactions and psychological distress, accounting for confounders.ResultsAmong the 551 study participants 31% reported severe psychological distress, 35% in those with job loss and 28% in those still employed but working less. Those who had significantly greater odds of high psychological distress were younger, female, had lost their job and had lower social interactions. The relationship between job loss and distress became non-significant when financial stress, and occupation were included in the regression model, but the protective effect of higher social interactions remained significant.DiscussionThere was a high prevalence of psychological distress in people losing work during the coronavirus pandemic. Age, gender, job loss and social interactions were strongly associated with distress. Interventions that promote social interaction may help to reduce distress during among people losing work during the COVID-19 pandemic.

Mass cytometry (MC) is a powerful research tool enabling high-dimensional analysis of single cells in suspension and within tissue sections following laser ablation. Here we describe the procedure of titrating metal-conjugated antibodies, to ensure that optimal levels of staining are achieved while minimizing nonspecific signals that may occur at high concentrations.

Mass cytometry (MC) is a powerful research tool enabling high-dimensional analysis of single cells in suspension and within tissue sections following laser ablation. Here we describe the procedure of titrating metal-conjugated antibodies, to ensure that optimal levels of staining are achieved while minimizing nonspecific signals that may occur at high concentrations.

Current treatment of severe malaria and associated cerebral malaria (CM) and respiratory distress syndromes are directed primarily at the parasite. Targeting the parasite has only partial efficacy in advanced infection, as neurological damage and respiratory distress are due to accumulation of host blood cells in the brain microvasculature and lung interstitium. Here, computational analysis identifies Ly6Clo monocytes as a major component of the immune infiltrate in both organs in a preclinical mouse model. Specifically targeting Ly6Clo monocyte precursors, identified by adoptive transfer, with immune-modifying particles (IMP) prevents experimental CM (ECM) in 50% of Plasmodium berghei ANKA-infected mice in early treatment protocols. Furthermore, treatment at onset of clinical ECM with 2 doses of a novel combination of IMP and anti-malarial drug artesunate results in 88% survival. This combination confers protection against ECM and mortality in late stage severe experimental malaria and provides a viable advance on current treatment regimens., Niewold, Cohen et al. identify Ly6Clo monocytes as a major component of immune cell sequestration in a mouse model of severe malaria. They show that combined immune-modifying particles and anti-malarial drug treatment at the onset of disease signs results in 88% survival of malaria-infected mice.

IRF8 (interferon-regulatory factor-8) plays a critical role in regulating myeloid cell differentiation. However, the role of this transcription factor in the development of Ly6C+ inflammatory monocytes and their migration to the infected brain has not been examined. We have previously shown that West Nile virus (WNV) infection of wild-type (WT) mice triggers a significant increase in numbers of Ly6C+ monocytes in the bone marrow. These cells traffic via the blood to the infected brain, where they give rise to proinflammatory macrophages. Here, we show that WNV-infected IRF8-deficient (IRF8-/-) mice had significantly reduced numbers of Ly6C+ monocytes in the periphery, with few of these cells found in the blood. Furthermore, low numbers of inflammatory monocyte-derived macrophages were observed in the brains of IRF8-/- mice throughout infection. Adoptive transfer of IRF8-/- Ly6C+ monocytes demonstrated that these cells were intrinsically unable to traffic to the inflamed brain. Low expression of the chemokine receptor CCR2 and integrin VLA-4 by IRF8-/- monocytes likely contributed to this defect, as the interactions between these proteins and their ligands are critical for monocyte egress and migration to inflammatory foci. These data highlight a critical role for IRF8 in inflammatory monocyte differentiation and migration during WNV infection.

Highlights • Virus encephalitis and EAE drive marked myeloid generation and migration into the CNS. • Large numbers of antigen-specific T cells infiltrate the CNS in both diseases. • In viral encephalitis immigrating monocytes differentiate into lethal macrophages. • In EAE immigrating monocytes differentiate into dendritic cells. • This differential regulation in the inflamed CNS is poorly understood., Over the last three decades it has become increasingly clear that monocytes, originally thought to have fixed, stereotypic responses to foreign stimuli, mediate exquisitely balanced protective and pathogenic roles in disease and immunity. This balance is crucial in core functional organs, such as the central nervous system (CNS), where minor changes in neuronal microenvironments and the production of immune factors can result in significant disease with fatal consequences or permanent neurological sequelae. Viral encephalitis and multiple sclerosis are examples of important human diseases in which the pathogenic contribution of monocytes recruited from the bone marrow plays a critical role in the clinical expression of disease, as they differentiate into macrophage or dendritic cells in the CNS to carry out effector functions. While antigen-specific lymphocyte populations are central to the adaptive immune response in both cases, in viral encephalitis a prominent macrophage infiltration may mediate immunopathological damage, seizure induction, and death. However, the autoimmune response to non-replicating, non-infectious, but abundant, self antigen has a different disease progression, associated with differentiation of significant numbers of infiltrating monocytes into dendritic cells in the CNS. Whilst a predominant presence of macrophages or dendritic cells in the inflamed CNS in viral encephalitis or multiple sclerosis is well described, the way in which the inflamed CNS mobilizes monocytes in the bone marrow to migrate to the CNS and the key drivers that lead to these specific differentiation pathways in vivo are not well understood. Here we review the current understanding of factors facilitating inflammatory monocyte generation, migration and entry into the brain, as well as their differentiation towards macrophages or dendritic cells in viral and autoimmune disease in relation to their respective disease outcomes.

Mosquito-borne viruses can cause severe inflammatory diseases and there are limited therapeutic solutions targeted specifically at virus-induced inflammation. Chikungunya virus (CHIKV), a re-emerging alphavirus responsible for several outbreaks worldwide in the past decade, causes debilitating joint inflammation and severe pain. Here, we show that CHIKV infection activates the NLRP3 inflammasome in humans and mice. Peripheral blood mononuclear cells isolated from CHIKV-infected patients showed elevated NLRP3, caspase-1 and interleukin-18 messenger RNA expression and, using a mouse model of CHIKV infection, we found that high NLRP3 expression was associated with peak inflammatory symptoms. Inhibition of NLRP3 activation using the small-molecule inhibitor MCC950 resulted in reduced CHIKV-induced inflammation and abrogated osteoclastogenic bone loss and myositis, but did not affect in vivo viral replication. Mice treated with MCC950 displayed lower expression levels of the cytokines interleukin-6, chemokine ligand 2 and tumour necrosis factor in joint tissue. Interestingly, MCC950 treatment abrogated disease signs in mice infected with a related arthritogenic alphavirus, Ross River virus, but not in mice infected with West Nile virus-a flavivirus. Here, using mouse models of alphavirus-induced musculoskeletal disease, we demonstrate that NLRP3 inhibition in vivo can reduce inflammatory pathology and that further development of therapeutic solutions targeting inflammasome function could help treat arboviral diseases.

Neurotropic flaviviruses are transmitted by arthropod vectors largely in an enzootic cycle that frequently involves humans incidentally. They are perhaps the most widespread of all viruses and continue to pose a threat, with increasing global warming, air travel and the extension of their insect vector habitat due to expanding human activity. Infection by these viruses is associated with a significant immunopathological response in a minority of individuals who, if they survive, may endure permanent neurological sequelae. While universal immunisation remains the ideal to prevent infection, progress has been slow and even available vaccines may not reach target populations. Unfortunately, our understanding of the interaction of these viruses with the mammalian host is still rudimentary, making current treatment approaches to disease at best empirical. However, recently, in addition to inhibition of the immunopathogenic activity of cells in situ, approaches to reducing the massive pathogenic leukocyte immigration into the central nervous system (CNS) have targeted monocytes with significant success in animal models. The universality of this population across a wide spectrum of diseases may enable a finely tuned approach to reducing the pathogenic component in encephalitis without interfering with the generation of immunity.

Inflammatory bowel disease (IBD) is a group of disorders that are characterized by chronic, uncontrolled inflammation in the intestinal mucosa. Although the aetiopathogenesis is poorly understood, it is widely believed that IBD stems from a dysregulated immune response towards otherwise harmless commensal bacteria. Chemokines induce and enhance inflammation through their involvement in cellular trafficking. Reducing or limiting the influx of these proinflammatory cells has previously been demonstrated to attenuate inflammation. CXCR3, a chemokine receptor in the CXC family that binds to CXCL9, CXCL10 and CXCL11, is strongly overexpressed in the intestinal mucosa of IBD patients. We hypothesised that CXCR3 KO mice would have impaired cellular trafficking, thereby reducing the inflammatory insult by proinflammatory cell and attenuating the course of colitis. To investigate the role of CXCR3 in the progression of colitis, the development of dextran sulfate sodium (DSS)-induced colitis was investigated in CXCR3-/- mice over 9 days. This study demonstrated attenuated DSS-induced colitis in CXCR3-/- mice at both the macroscopic and microscopic level. Reduced colitis correlated with lower recruitment of neutrophils (p = 0.0018), as well as decreased production of IL-6 (p

Mosquito-borne flaviviruses are a major current and emerging threat, affecting millions of people worldwide. Global climate change, combined with increasing proximity of humans to animals and mosquito vectors by expansion into natural habitats, coupled with the increase in international travel, have resulted in significant spread and concomitant increase in the incidence of infection and severe disease. Although neuroinvasive disease has been well described for some viral infections such as Japanese Encephalitis virus (JEV) and West Nile virus (WNV), others such as dengue virus (DENV) have recently displayed an emerging pattern of neuroinvasive disease, distinct from the previously observed, systemically-induced encephalomyelopathy. In this setting, the immune response is a crucial component of host defence, in preventing viral dissemination and invasion of the central nervous system (CNS). However, subversion of the anti-viral activities of macrophages by flaviviruses can facilitate viral replication and spread, enhancing the intensity of immune responses, leading to severe immune-mediated disease which may be further exacerbated during the subsequent infection with some flaviviruses. Furthermore, in the CNS myeloid cells may be responsible for inducing specific inflammatory changes, which can lead to significant pathological damage during encephalitis. The interaction of virus and cells of the myeloid lineage is complex, and this interaction is likely responsible at least in part, for crucial differences between viral clearance and pathology. Recent studies on the role of myeloid cells in innate immunity and viral control, and the mechanisms of evasion and subversion used by flaviviruses are rapidly advancing our understanding of the immunopathological mechanisms involved in flavivirus encephalitis and will lead to the development of therapeutic strategies previously not considered.

Inflammatory monocyte-derived effector cells play an important role in the pathogenesis of numerous inflammatory diseases. However, no treatment option exists that is capable of modulating these cells specifically. We show that infused negatively charged, immune-modifying microparticles (IMPs), derived from polystyrene, microdiamonds, or biodegradable poly(lactic-co-glycolic) acid, were taken up by inflammatory monocytes, in an opsonin-independent fashion, via the macrophage receptor with collagenous structure (MARCO). Subsequently, these monocytes no longer trafficked to sites of inflammation; rather, IMP infusion caused their sequestration in the spleen through apoptotic cell clearance mechanisms and, ultimately, caspase-3-mediated apoptosis. Administration of IMPs in mouse models of myocardial infarction, experimental autoimmune encephalomyelitis, dextran sodium sulfate-induced colitis, thioglycollate-induced peritonitis, and lethal flavivirus encephalitis markedly reduced monocyte accumulation at inflammatory foci, reduced disease symptoms, and promoted tissue repair. Together, these data highlight the intricate interplay between scavenger receptors, the spleen, and inflammatory monocyte function and support the translation of IMPs for therapeutic use in diseases caused or potentiated by inflammatory monocytes.

In recent years, nanodiamonds have emerged from primarily an industrial and mechanical applications base, to potentially underpinning sophisticated new technologies in biomedical and quantum science. Nanodiamonds are relatively inexpensive, biocompatible, easy to surface functionalise and optically stable. This combination of physical properties are ideally suited to biological applications, including intracellular labelling and tracking, extracellular drug delivery and adsorptive detection of bioactive molecules. Here we describe some of the methods and challenges for processing nanodiamond materials, detection schemes and some of the leading applications currently under investigation.

Monocytes are a heterogeneous population of bone marrow-derived cells that are recruited to sites of infection and inflammation in many models of human diseases, including those of the central nervous system (CNS). Ly6Chi/CCR2hi inflammatory monocytes have been identified as the circulating precursors of brain macrophages, dendritic cells and arguably microglia in experimental autoimmune encephalomyelitis; Alzheimer’s disease; stroke; and more recently in CNS infection caused by Herpes simplex virus, murine hepatitis virus, Theiler’s murine encephalomyelitis virus, Japanese encephalitis virus and West Nile virus. The precise differentiation pathways and functions of inflammatory monocyte-derived populations in the inflamed CNS remains a contentious issue, especially in regard to the existence of monocyte-derived microglia. Furthermore, the contributions of monocyte-derived subsets to viral clearance and immunopathology are not well-defined. Thus, understanding the pathways through which inflammatory monocytes migrate to the brain and their functional capacity within the CNS is critical to inform future therapeutic strategies. This review discusses some of the key aspects of inflammatory monocyte trafficking to the brain and addresses the role of these cells in viral encephalitis.