Redefining the human corneal immune compartment using dynamic intravital imaging.

The healthy human cornea is a uniquely transparent sensory tissue where immune responses are tightly controlled to preserve vision. The cornea contains immune cells that are widely presumed to be intraepithelial dendritic cells (DCs). Corneal immune cells have diverse cellular morphologies and morphological alterations are used as a marker of inflammation and injury. Based on our imaging of corneal T cells in mice, we hypothesized that many human corneal immune cells commonly defined as DCs are intraepithelial lymphocytes (IELs). To investigate this, we developed functional in vivo confocal microscopy (Fun-IVCM) to investigate cell dynamics in the human corneal epithelium and stroma. We show that many immune cells resident in the healthy human cornea are T cells. These corneal IELs are characterized by rapid, persistent motility and interact with corneal DCs and sensory nerves. Imaging deeper into the corneal stroma, we show that crawling macrophages and rare motile T cells patrol the tissue. Furthermore, we identify altered immune cell behaviors in response to short-term contact lens wear (acute inflammatory stimulus), as well as in individuals with allergy (chronic inflammatory stimulus) that was modulated by therapeutic intervention. These findings redefine current understanding of immune cell subsets in the human cornea and reveal how resident corneal immune cells respond and adapt to chronic and acute stimuli.

Ocular Distribution of the Renin-Angiotensin-Aldosterone System in the Context of the SARS-CoV-2 Pandemic.

The COVID-19 pandemic has resulted in an unprecedented impact on global health, economy, and way of life. SARS-CoV-2, the virus responsible for the disease, utilizes the ACE2 receptor found on host cells to mediate entry, replication, and infection. Numerous studies have elucidated the presence of many components of the renin-angiotensin-aldosterone system (RAAS) in the eye, including the ACE2 receptor. Considering this, and the anatomical vulnerability that the exposed ocular surface offers with its interconnectedness to the respiratory system, there is a theoretical risk of pathogen entry from the ocular route as well as the development of COVID-19-associated eye disease. Despite this, the actual epidemiological data demonstrates low ocular symptoms, possibly due to differing ACE2 receptor expression across age, ethnicity, and sex coupled with the protective properties of tears. We summarize the current literature on ocular RAAS with specific focus on the ACE2 receptor and its interplay with the SARS-CoV-2 virus.

Tissue resident memory T cells inhabit the deep human conjunctiva.

Mucosal linings of the body, including the conjunctiva, are enriched in tissue-resident memory T cells (TRMs) whose defining feature is their continual tissue protection that does not rely on migration to lymphoid organs to elicit immune responses. Hitherto, conjunctival TRMs have only been identified in the superficial epithelium. This work aims to develop a more complete understanding of the conjunctival immunological capacity by investigating the presence of TRMs within the deeper, more stable layers of the healthy human conjunctiva. Using immunofluorescence microscopy and antibodies against CD3, CD4, CD69 and HLA-DR on bulbar conjunctival biopsies obtained from 7 healthy adults (age range = 32-77 years; females = 4), we identified CD69+TRM subsets in all layers of the human conjunctiva: the superficial epithelium, the basal epithelium, the adenoid, and the fibrous layers. Interestingly, the adenoid layer showed significantly higher densities of both CD4 and CD8 TRMs when compared to the fibrous layer and conjunctival epithelia. Additionally, CD4 TRMs predominated significantly over CD8 TRMs in the adenoid layer. The abundance of deep conjunctival CD69+TRMs within the healthy human may suggest the presence of defence mechanisms capable of inducing long-term immunogenic memory. Understanding this spatial distribution of conjunctival CD69+TRMs is essential to improving mucosal vaccine design.

Meteorological Drought Variability and Its Impact on Wheat Yields across South Africa.

Drought is one of the natural hazards that have negatively affected the agricultural sector worldwide. The aims of this study were to track drought characteristics (duration (DD), severity (DS), and frequency (DF)) in South Africa between 2002 and 2021 and to evaluate its impact on wheat production. Climate data were collected from the South African Weather Service (SAWS) along with wheat yield data from the Department of Agriculture, Forestry and Fisheries (2002-2021). The standard precipitation index (SPI) was calculated on 3-, 6-, 9-, and 12-month time scales, and the trend was then tracked using the Mann-Kendall (MK) test. To signify the climatic effects on crop yield, the standardized yield residual series (SYRS) was computed along with the crop-drought resilience factor (CR) on a provincial scale (2002-2021). The output of the SPI analysis for 32 stations covering all of South Africa indicates a drought tendency across the country. On a regional scale, western coastal provinces (WES-C and NR-C) have been more vulnerable to meteorological droughts over the past 20 years. Positive correlation results between SYRS and wheat yield indicate that the WES-C province was highly influenced by drought during all stages of wheat growth (Apr-Nov). Historical drought spells in 2003, 2009, and 2010 with low CR = 0.64 caused the province to be highly impacted by the negative impacts of droughts on yield loss. Overall, drought events have historically impacted the western part of the country and dominated in the coastal area. Thus, mitigation plans should be commenced, and priority should be given to this region. These findings can assist policymakers in budgeting for irrigation demand in rainfed agricultural regions.

Geospatial Analysis of COVID-19: A Scoping Review.

The outbreak of SARS-CoV-2 in Wuhan, China in late December 2019 became the harbinger of the COVID-19 pandemic. During the pandemic, geospatial techniques, such as modeling and mapping, have helped in disease pattern detection. Here we provide a synthesis of the techniques and associated findings in relation to COVID-19 and its geographic, environmental, and socio-demographic characteristics, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) methodology for scoping reviews. We searched PubMed for relevant articles and discussed the results separately for three categories: disease mapping, exposure mapping, and spatial epidemiological modeling. The majority of studies were ecological in nature and primarily carried out in China, Brazil, and the USA. The most common spatial methods used were clustering, hotspot analysis, space-time scan statistic, and regression modeling. Researchers used a wide range of spatial and statistical software to apply spatial analysis for the purpose of disease mapping, exposure mapping, and epidemiological modeling. Factors limiting the use of these spatial techniques were the unavailability and bias of COVID-19 data-along with scarcity of fine-scaled demographic, environmental, and socio-economic data-which restrained most of the researchers from exploring causal relationships of potential influencing factors of COVID-19. Our review identified geospatial analysis in COVID-19 research and highlighted current trends and research gaps. Since most of the studies found centered on Asia and the Americas, there is a need for more comparable spatial studies using geographically fine-scaled data in other areas of the world.

Exploring the Frequency, Intensity, and Duration of Loneliness: A Latent Class Analysis of Data from the BBC Loneliness Experiment.

Almost all measures of loneliness have been developed without discussing how to best conceptualize and assess the severity of loneliness. In the current study, we adapted the four-item UCLA, so that it continued to measure frequency of loneliness, but also assessed intensity and duration, providing a measure of other aspects of loneliness severity. Using data from participants resident in the UK who completed the BBC Loneliness Experiment (N = 36,767; F = 69.6%) and Latent Class Profile Analyses, we identified four groups of people who scored high on loneliness on at least one of the three severity measures. Duration of loneliness often over months or years seemed to be particularly important in distinguishing groups. Further, group membership was predicted by important demographic and psychological variables. We discuss the findings in terms of implications for research and practice. We highlight the need to explore these profiles longitudinally to investigate how membership predicts later mental and physical health, and well-being.

20 years since the Herpetic Eye Disease Study: Lessons, developments and applications to clinical practice.

Herpes Simplex Virus (HSV) is the most common virus that causes eye disease. Although around 60% of the world's population are seropositive for HSV antigens, fortunately, it is estimated that only 1% of seropositive individuals develop eye disease. The most common ocular manifestation of HSV is keratitis, while uveitis and retinal necrosis occur in a small number of cases. HSV keratitis is a debilitating disease, for several reasons: pain , photophobia, and vision loss in acute disease, latency of the virus which leads to infection reactivation from various triggers, scarring, and neovascularisation, leading to permanent vision loss with poor visual rehabilitation prospects. The Herpetic Eye Disease Study (HEDS) was a landmark series of randomised controlled trials in the 1990s that set the benchmark for evidence-based treatment guidelines for anterior eye herpetic disease. Since this time, there has been a change in the distribution of seroprevalence of herpes in the community, a simplified diagnostic classification, advances in treatment options, an emergence of new and a better understanding of risk factors, and discoveries in science that show promise for vaccine and novel future treatments. However, many of the principles of the HEDS study remain rightly entrenched in clinical practice. In this article, the HEDS study is revisited 20 years on through the lens of published literature, to determine current best practise and look towards the future.

The Role of Tissue Resident Memory CD4 T Cells in Herpes Simplex Viral and HIV Infection.

Tissue-resident memory T cells (TRM) were first described in 2009. While initially the major focus was on CD8+ TRM, there has recently been increased interest in defining the phenotype and the role of CD4+ TRM in diseases. Circulating CD4+ T cells seed CD4+ TRM, but there also appears to be an equilibrium between CD4+ TRM and blood CD4+ T cells. CD4+ TRM are more mobile than CD8+ TRM, usually localized deeper within the dermis/lamina propria and yet may exhibit synergy with CD8+ TRM in disease control. This has been demonstrated in herpes simplex infections in mice. In human recurrent herpes infections, both CD4+ and CD8+ TRM persisting between lesions may control asymptomatic shedding through interferon-gamma secretion, although this has been more clearly shown for CD8+ T cells. The exact role of the CD4+/CD8+ TRM axis in the trigeminal ganglia and/or cornea in controlling recurrent herpetic keratitis is unknown. In HIV, CD4+ TRM have now been shown to be a major target for productive and latent infection in the cervix. In HSV and HIV co-infections, CD4+ TRM persisting in the dermis support HIV replication. Further understanding of the role of CD4+ TRM and their induction by vaccines may help control sexual transmission by both viruses.