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Aim: To determine the expression and distribution of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the normal human iris and ciliary body. Methods: Seven postmortem human eyes were fixed [...]

Background: Experiences of end-of-life care and early bereavement during the COVID-19 pandemic are poorly understood. Aim: To identify clinical and demographic risk factors for sub-optimal end-of-life care and pandemic-related challenges prior to death and in early bereavement, to inform clinical practice, policy and bereavement support. Design: Online national survey of adults bereaved in the UK (deaths between 16 March 2020 and 2 January 2021), recruited via media, social media, national associations and organisations. Setting/participants: 711 participants, mean age 49.5 (SD 12.9, range 18–90). 628 (88.6%) were female. Mean age of the deceased was 72.2 (SD 16.1, range miscarriage to 102 years). 311 (43.8%) deaths were from confirmed/suspected COVID-19. Results: Deaths in hospital/care home increased the likelihood of poorer experiences at the end of life; for example, being unable to visit or say goodbye as wanted (p < 0.001). COVID-19 was also associated with worse experiences before and after death; for example, feeling unsupported by healthcare professionals (p < 0.001), social isolation/loneliness (OR = 0.439; 95% CI: 0.261–0.739), and limited contact with relatives/friends (OR = 0.465; 95% CI: 0.254–0.852). Expected deaths were associated with a higher likelihood of positive end-of-life care experiences. The deceased being a partner or child also increased the likelihood of positive experiences, however being a bereaved partner strongly increased odds of social isolation/loneliness, for example, OR = 0.092 (95% CI: 0.028–0.297) partner versus distant family member. Conclusions: Four clear risk factors were found for poorer end-of-life care and pandemic-related challenges in bereavement: place, cause and expectedness of death, and relationship to the deceased. [ABSTRACT FROM AUTHOR]

Background/aim: Anterior uveitis is a common inflammatory ocular disease characterised by protein accumulation and leucocyte infiltration in the anterior chamber. The aim of this study was to determine the expression [...]

Schnitzler syndrome is a rare, auto inflammatory condition known to manifest with bone pain, urticarial rash, fevers, relapsing arthralgia, and fatigue. In this case report, we describe a patient who was diagnosed with Schnitzler Syndrome that had initially presented with a unilateral pressure-type headache with a sensation of a 'dagger' stabbing into the back of the eye. He also had an associated ipsilateral redness of the conjunctiva, eyelid swelling, subtle optic disc elevations bilaterally and facial flushing - but with no visual acuity, pupillary, or lacrimatory changes. Anterior segment, fundoscopy, intraocular pressures and extraocular muscle movements were otherwise normal. [ABSTRACT FROM AUTHOR]

Background: A detailed description of the natural history of acute Q fever, caused by infection with Coxiella burnetii. Aim: To significantly increase understanding of the illness. Design: Subjects with provisional acute Q fever (n=115) were recruited from primary care in rural Australia, and followed prospectively by interview and blood collection including for serological confirmation. A nested series of subjects with prolonged illness (cases), and those without (controls), were investigated in detail. Methods: Total phase I and phase II anti-C. burnetii antibodies were detected by complement fixation test; and IgG, IgM and IgA phase I and phase II titres by immunofluorescence. Flow cytometric analysis was conducted to enumerate circulating T cells subsets, B cells, monocytes and natural killer cells. Results: Serological testing confirmed acute Q fever in 73 subjects (63%). The acute illness featured fever, headache, sweats, fatigue and anorexia; and varied widely in severity, causing an average of 8 days in bed and 15 days out of work or other role in the first month of illness. The illness course varied from 2 days to greater than a year. No cases of chronic, localized Q fever infection, such as endocarditis, were identified. Neither severe nor prolonged illness were associated with persistence of C. burnetii DNA, altered patterns of C. burnetii-specific IgG, IgM or IgA antibody production, or altered leucocyte subsets. Conclusions: The severity of acute Q fever alone predicted prolonged duration. Further studies are warranted to better understand the pathophysiology of prolonged illness after acute Q fever. [ABSTRACT FROM AUTHOR]

Stem cell (SC) division, deployment, and differentiation are processes that contribute to corneal epithelial renewal. Until now studying the destiny of these cells in a living mammal has not been possible. However, the advent of inducible multicolor genetic tagging and powerful imaging technologies has rendered this achievable in the translucent and readily accessible murine cornea. K14CreERT2-Confetti mice that harbor two copies of the Brainbow 2.1 cassette, yielding up to 10 colors from the stochastic recombination of fluorescent proteins, were used to monitor K-14+ progenitor cell dynamics within the corneal epithelium in live animals. Multicolored columns of cells emerged from the basal limbal epithelium as they expanded and migrated linearly at a rate of 10.8 µm/day toward the central cornea. Moreover, the permanent expression of fluorophores, passed on from progenitor to progeny, assisted in discriminating individual clones as spectrally distinct streaks containing more than 1,000 cells within the illuminated area. The centripetal clonal expansion is suggestive that a single progenitor cell is responsible for maintaining a narrow corridor of corneal epithelial cells. Our data are in agreement with the limbus as the repository for SC as opposed to SC being distributed throughout the central cornea. This is the first report describing stem/progenitor cell fate determination in the murine cornea using multicolor genetic tracing. This model represents a powerful new resource to monitor SC kinetics and fate choice under homeostatic conditions, and may assist in assessing clonal evolution during corneal development, aging, wound-healing, disease, and following transplantation. S tem C ells 2015;33:157-169 [ABSTRACT FROM AUTHOR]

Abstract: Stem cell (SC) therapy is the main treatment modality for patients with limbal stem cell deficiency. If limbal epithelial stem cells (LESC) can be more readily identified, isolated and maintained ex vivo, patients could be treated with better quality grafts. With prior knowledge that vitronectin (VN) is present within the LESC niche and that it supports LESC in vitro, we postulated that VN receptors (integrins αvβ3/5) are expressed by, and can be used to identify and isolate LESC. Immunolocalization studies were conducted on human corneas. Corneas were also used to expand limbal epithelial cells from either biopsies or enzyme-dissociated tissue and αvβ3/5 expression determined by flow cytometry. Integrin expressing cells were isolated by magnetic activated cell sorting then assessed by immunocytology, colony forming efficiency, RT-PCR and microarray analysis. Integrin αvβ5+ cells co-localized to N-cadherin+/CK-15+ putative LESC. αvβ5 was restricted to less than 4% of the total limbal epithelial cells, which expressed higher levels of CK-15 and formed more colonies compared to αvβ5− cells. Transcriptional profiling of αvβ5+/− cells by microarray identified several highly expressed interferon-inducible genes, which localize to putative LESC. Integrin αvβ5 is a candidate LESC marker since its expression is restricted to the limbus and αvβ5+ limbal epithelial cells have phenotypic and functional properties of LESC. Knowledge of the niche's molecular composition and the genes expressed by its SC will facilitate isolation and maintenance of these cells for therapeutic purposes. [Copyright &y& Elsevier]

Objective: To examine the role of mast cells (MCs), cytokines, and matrix metalloproteinases (MMPs) following ultraviolet B (UVB) radiation in cutaneous lupus erythematosus (CLE). Methods: Immunohistochemistry was used to determine the presence of MCs and the expression of MMP-1, MMP-9, interleukin (IL)-15, and CCL5//RANTES in skin from patients with CLE. Human keratinocytes were exposed to varying doses of UVB and supernatants were collected and assessed for IL-15, CCL5, MMP-1, and MMP-9 by protein assays. MC migration was determined against supernatants from UVB-treated keratinocytes. Results: MCs in the skin of patients with CLE were significantly increased. MMP-1 and MMP-9 expression was abundant in these lesions. Intense reactivity for IL-15 and CCL5 was found in skin, particularly in epidermal keratinocytes, from patients with CLE. UVB irradiation induced IL-15, CCL5, MMP-1, and MMP-9 production from keratinocytes in a dose- and time-dependent manner. Supernatants obtained from UVB-treated keratinocytes induced MC migration, which was attenuated by anti-IL-15 and anti-CCL5 neutralizing antibodies. IL-15 induced MC-derived MMP production. Conclusions: Our results indicate that MCs and MMPs may play a role in the skin inflammation in CLE. MC recruitment as well as MMP production may be perpetuated by UV irradiation through locally released mediators. [ABSTRACT FROM AUTHOR]