Pediatric orbital lesions: neoplastic extraocular soft-tissue lesions.

Pediatric neoplastic extraocular soft-tissue lesions in the orbit are uncommon. Early multimodality imaging work-up and recognition of the key imaging features of these lesions allow narrowing of the differential diagnoses in order to direct timely management. In this paper, the authors present a multimodality approach to the imaging work-up of these lesions and highlight the use of ocular ultrasound as a first imaging modality where appropriate. We will discuss vascular neoplasms (congenital hemangioma, infantile hemangioma), optic nerve lesions (meningioma, optic nerve glioma), and other neoplastic lesions (plexiform neurofibroma, teratoma, chloroma, rhabdomyosarcoma, infantile fibrosarcoma, schwannoma).

Quality of vision and tear film osmolarity.

SIGNIFICANCE: We evaluate the relationship between tear film osmolarity measurements and quality of vision in patients presenting for routine eye clinic appointments. We found that the hyperosmolar group (>316 mOsm/L) had a worse quality-of-vision score than the normal osmolarity group, with glare being the most problematic symptom. PURPOSE: Quality of vision is a perception and measure of real-world vision, which is not measured routinely in a clinical setting. This study aimed to evaluate the relationship between tear film osmolarity measurements and quality of vision in patients presenting for routine eye clinic appointments. METHODS: This was an observational nonrandomized study. The participants were placed in groups based on tear film osmolarity (normal, ≤316 mOsm/L; hyperosmolar, >316 mOsm/L; or a difference of >8 mOsm/L between each eye). Thirty-three participants were enrolled in the study, of whom 22 were deemed to have a hyperosmolar tear film. A 30-item questionnaire including 10 symptoms rated on scales of frequency, severity, and bothersomeness was administered to participants in both groups. The quality-of-vision score ranged from 25 to 100 points, with lower scores indicating better quality of vision. RESULTS: The hyperosmolar group had a significantly worse quality-of-vision score than the normal osmolarity group across all three scales; mean differences for frequency, severity, and bothersomeness were 12.66 ± 9.75 (p=0.003), 9.44 ± 7.45 (p=0.003), and 11.90 ± 11.14 (p=0.008), respectively. Of the 10 symptoms that were included in the questionnaire, glare was the most problematic in the hyperosmolar group. CONCLUSIONS: In this study, we demonstrated a significant relationship between tear film hyperosmolarity and quality of vision, as patients with hyperosmolar tear films had worse quality of vision.

Pediatric orbital lesions: ocular pathologies.

Orbital pathologies can be broadly classified as ocular, extra-ocular soft-tissue (non-neoplastic and neoplastic), osseous, and traumatic. In part 1 of this orbital series, the authors will discuss the differential diagnosis and key imaging features of pediatric ocular pathologies. These include congenital and developmental lesions (microphthalmos, anophthalmos, persistent fetal vasculature, coloboma, morning glory disc anomaly, retinopathy of prematurity, Coats disease), optic disc drusen, infective and inflammatory lesions (uveitis, toxocariasis, toxoplasmosis), and ocular neoplasms (retinoblastoma, retinal hamartoma, choroidal melanoma, choroidal nevus). This pictorial review provides a practical approach to the imaging work-up of these anomalies with a focus on ocular US as the first imaging modality and additional use of CT and/or MRI for the evaluation of intracranial abnormalities. The characteristic imaging features of the non-neoplastic mimics of retinoblastoma, such as persistent fetal vasculature and Coats disease, are also highlighted.

Pediatric orbital lesions: bony and traumatic lesions.

Orbital pathologies can be broadly classified as ocular lesions, extraocular soft-tissue pathologies (non-neoplastic and neoplastic), and bony and traumatic lesions. In this paper, we discuss the key imaging features and differential diagnoses of bony and traumatic lesions of the pediatric orbit and globe, emphasizing the role of CT and MRI as the primary imaging modalities. In addition, we highlight the adjunctive role of ocular sonography in the diagnosis of intraocular foreign bodies and discuss the primary role of sonography in the diagnosis of traumatic retinal detachment.

Pediatric orbital lesions: non-neoplastic extraocular soft-tissue lesions.

Orbital pathologies can be broadly classified as ocular, extraocular soft-tissue (non-neoplastic and neoplastic), osseous, and traumatic. In this paper, we discuss the key imaging features and differential diagnoses of congenital and developmental lesions (dermoid cyst, dermolipoma), infective and inflammatory pathologies (pre-septal cellulitis, orbital cellulitis, optic neuritis, chalazion, thyroid ophthalmopathy, orbital pseudotumor), and non-neoplastic vascular anomalies (venous malformation, lymphatic malformation, carotid-cavernous fistula), emphasizing the key role of CT and MRI in the imaging work-up. In addition, we highlight the adjunctive role of ocular ultrasound in the diagnosis of dermoid cyst and chalazion, and discuss the primary role of ultrasound in the diagnosis of vascular malformations.

An ancient polymorphic regulatory region within the BDNF gene associated with obesity modulates anxiety-like behaviour in mice and humans.

Obesity and anxiety are morbidities notable for their increased impact on society during the recent COVID-19 pandemic. Understanding the mechanisms governing susceptibility to these conditions will increase our quality of life and resilience to future pandemics. In the current study, we explored the function of a highly conserved regulatory region (BE5.1) within the BDNF gene that harbours a polymorphism strongly associated with obesity (rs10767664; p = 4.69 × 10-26). Analysis in primary cells suggested that the major T-allele of BE5.1 was an enhancer, whereas the obesity-associated A-allele was not. However, CRISPR/CAS9 deletion of BE5.1 from the mouse genome (BE5.1KO) produced no significant effect on the expression of BDNF transcripts in the hypothalamus, no change in weight gain after 28 days and only a marginally significant increase in food intake. Nevertheless, transcripts were significantly increased in the amygdala of female mice and elevated zero maze and marble-burying tests demonstrated a significant increase in anxiety-like behaviour that could be reversed by diazepam. Consistent with these observations, human GWAS cohort analysis demonstrated a significant association between rs10767664 and anxiousness in human populations. Intriguingly, interrogation of the human GTEx eQTL database demonstrated no effect on BDNF mRNA levels associated with rs10767664 but a highly significant effect on BDNF-antisense (BDNF-AS) gene expression and splicing. The subsequent observation that deletion of BE5.1 also significantly reduced BDNF-AS expression in mice suggests a novel mechanism in the regulation of BDNF expression common to mice and humans, which contributes to the modulation of mood and anxiety in both species.

Connecting groups and behaviours: A network analysis of identity-infused behaviours.

Research in the social identity tradition acknowledges the multiplicity of our identities and the implications that identity compatibility has for our health and well-being. However, current measures of multiple group membership have not yet captured the richness and complexity of our social identity networks at the wider sample level, and data regarding the different behaviours typically associated with different group memberships are scarce. Adopting a network approach, we explore the co-occurrence of different group memberships within an individual (identity-by-identity network), the behaviours that are shared among identities (behaviour-by-identity network), and whether identities that are shared also share common behaviours (identity-by-behaviour network). An online survey asked participants (N = 286) to list the groups they are part of, as well as the behaviours viewed to be typical of group members. The networks identified several identities and behaviours to significantly co-occur at a rate both higher and lower than chance. Networks were found to be low in modularity; there was no evidence of clustering within the data. Permutation analyses demonstrated the overall structure of the networks to be significantly different than expected by chance. The co-occurrences identified serve as a meaningful resource for those conducting research into identities, group norms and their associated behaviours.

The cost-effectiveness of adding an ultrasound corticosteroid and local anaesthetic injection to advice and education for hip osteoarthritis.

OBJECTIVES: Evidence for the comparative cost-effectiveness of intra-articular corticosteroid injection in people with hip osteoarthritis (OA) remains unclear. This study investigated the cost-effectiveness of best current treatment (BCT) comprising advice and education plus a single ultrasound-guided intra-articular hip injection (USGI) of 40 mg triamcinolone acetonide and 4 ml 1% lidocaine hydrochloride (BCT+US-T) versus BCT alone. METHODS: A trial-based cost-utility analysis of BCT+US-T compared with BCT was undertaken over 6 months. Patient-level cost data were obtained, and effectiveness was measured in terms of quality-adjusted life years (QALYs), allowing the calculation of cost per QALY gained from a United Kingdom (UK) National Health Service (NHS) perspective. RESULTS: BCT+US-T was associated with lower mean NHS costs (BCT+US-T minus BCT: £-161.6, 95% CI: £-583.95 to £54.18) and small but significantly higher mean QALYs than BCT alone over 6 months (BCT+US-T minus BCT: 0.0487, 95% CI: 0.0091, 0.0886). In the base case, BCT+US-T was the most cost-effective and dominated BCT alone. Differences in total costs were driven by number of visits to NHS consultants, private physiotherapists, and chiropractors, and hip surgery, which were more common with BCT alone than BCT+US-T. CONCLUSION: Intra-articular corticosteroid injection plus BCT (BCT+US-T) for patients with hip OA results in lower costs and better outcomes, and is highly cost-effective, compared with BCT alone. TRIAL REGISTRATION: EudraCT: 2014-003412-37 (August 8, 2015) and registered with Current Controlled Trials: ISRCTN 50550256 (July 28, 2015). TRIAL PROTOCOL: Full details of the trial protocol can be found in the Supplementary Appendix, available with the full text of this article at https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-018-2153-0#citeas. DOI: doi.org/10.1186/s12891-018-2153-0.

Endangered shark species traded as "cação" in São Paulo during the COVID-19 lockdown: DNA-barcoding a snapshot of products.

BACKGROUND: Elasmobranch populations are declining, predominantly driven by overfishing, and over a third of global sharks, rays, and chimeras are estimated to be threatened with extinction. In terms of trade, Brazil is ranked the eleventh-largest shark producer and the top importer of shark meat in the world. Research has shown that elasmobranchs are sold in Brazil under the name "cação" (a generic designation for cartilaginous fish) to overcome consumer resistance. METHODOLOGY AND RESULTS: This study used DNA barcoding to investigate the sale of sharks in the State of São Paulo during the COVID-19 lockdown. A total of 35 samples of "cação" were analysed, revealing six different shark species on sale, including Carcharhinus falciformis, Carcharhinus signatus, Carcharias taurus, Isurus oxyrinchus, and Isurus paucus, that are threatened with extinction according to the IUCN red list. This study demonstrates that vulnerable elasmobranchs are being commercialised under the label "cação" in the São Paulo State and Brazil. CONCLUSIONS: Comparison of shark products traded before and during the COVID-19 pandemic showed no significant difference, suggesting lockdown did not affect patterns of species commercialisation. Effective fisheries and sale monitoring, correct product labelling legislation and increased consumer awareness that "cação" is shark are needed for appropriate conservation and management of shark populations in Brazil.

An inverse agonist of orphan receptor GPR61 acts by a G protein-competitive allosteric mechanism.

GPR61 is an orphan GPCR related to biogenic amine receptors. Its association with phenotypes relating to appetite makes it of interest as a druggable target to treat disorders of metabolism and body weight, such as obesity and cachexia. To date, the lack of structural information or a known biological ligand or tool compound has hindered comprehensive efforts to study GPR61 structure and function. Here, we report a structural characterization of GPR61, in both its active-like complex with heterotrimeric G protein and in its inactive state. Moreover, we report the discovery of a potent and selective small-molecule inverse agonist against GPR61 and structural elucidation of its allosteric binding site and mode of action. These findings offer mechanistic insights into an orphan GPCR while providing both a structural framework and tool compound to support further studies of GPR61 function and modulation.

Press Releases of Drug-Related Randomized Trial Results Prior to Publication in High-Impact Journals: an Observational Study.

IMPORTANCE: Results from high-profile randomized controlled trials (RCTs) are routinely reported through press release months prior to peer-reviewed publication. There are potential benefits to press releases (e.g., knowledge dissemination, ensuring regulatory compliance), but also potential drawbacks (e.g., selective reporting, positive "spin"). OBJECTIVE: To characterize the practice of press release predating the publication of a drug-related RCT in a peer-reviewed journal ("preemptive press release"), including factors associated with this practice. DESIGN, SETTING, AND PARTICIPANTS: We systematically reviewed all RCTs of medications published between 2015 and 2019 in the New England Journal of Medicine (NEJM), Journal of the American Medical Association (JAMA), and Lancet. Press releases were identified using a systematic search of the grey literature (e.g., press release databases, study sponsor websites). An RCT was considered to have a preemptive press release if the press release was published at least three months (90 days) prior to the date of publication in a peer-reviewed journal. MAIN OUTCOMES AND MEASURES: Presence of preemptive press release, defined as a press-release at least 90 days prior to the date of publication in a peer-reviewed journal. As secondary measures for dissemination, we also assessed citation count and Altmetric score. RESULTS: We identified 988 RCTs, of which 172 (17%) had a press release published at least 90 days before the date of peer-reviewed publication. Press releases were published a median of 246 days (interquartile range [IQR] 169-366 days) before publication in a peer-reviewed journal. In the multivariable logistic regression model, the strongest predictor of having a preemptive press release was funding by a pharmaceutical company (odds ratio 13, 95% CI 7, 25). Approximately 85% of RCTs with preemptive press releases had a positive primary outcome and, concordantly, 81% of the corresponding press releases had a positive headline. Multivariable regression models identified studies with a preemptive press release had a similar Altmetric score (median - 15, 95% CI - 33, 12) and higher median citation count (median 22 [95% CI 10 to 33] compared to studies without a preemptive press release. CONCLUSIONS AND RELEVANCE: Preemptive press releases were common, most often issued for trials funded by a pharmaceutical company, and typically preceded publication in a peer-reviewed journal by approximately eight months.

Genome-wide study of longitudinal brain imaging measures of multiple sclerosis progression across six clinical trials.

While the genetics of MS risk susceptibility are well-described, and recent progress has been made on the genetics of disease severity, the genetics of disease progression remain elusive. We therefore investigated the genetic determinants of MS progression on longitudinal brain MRI: change in brain volume (BV) and change in T2 lesion volume (T2LV), reflecting progressive tissue loss and increasing disease burden, respectively. We performed genome-wide association studies of change in BV (N = 3401) and change in T2LV (N = 3513) across six randomized clinical trials from Biogen and Roche/Genentech: ADVANCE, ASCEND, DECIDE, OPERA I & II, and ORATORIO. Analyses were adjusted for randomized treatment arm, age, sex, and ancestry. Results were pooled in a meta-analysis, and were evaluated for enrichment of MS risk variants. Variant colocalization and cell-specific expression analyses were performed using published cohorts. The strongest peaks were in PTPRD (rs77321193-C/A, p = 3.9 × 10-7) for BV change, and NEDD4L (rs11398377-GC/G, p = 9.3 × 10-8) for T2LV change. Evidence of colocalization was observed for NEDD4L, and both genes showed increased expression in neuronal and/or glial populations. No association between MS risk variants and MRI outcomes was observed. In this unique, precompetitive industry partnership, we report putative regions of interest in the neurodevelopmental gene PTPRD, and the ubiquitin ligase gene NEDD4L. These findings are distinct from known MS risk genetics, indicating an added role for genetic progression analyses and informing drug discovery.

A novel in vitro model to study prolonged Pseudomonas aeruginosa infection in the cystic fibrosis bronchial epithelium.

Pseudomonas aeruginosa (PA) is known to chronically infect airways of people with cystic fibrosis (CF) by early adulthood. PA infections can lead to increased airway inflammation and lung tissue damage, ultimately contributing to decreased lung function and quality of life. Existing models of PA infection in vitro commonly utilize 1-6-hour time courses. However, these relatively early time points may not encompass downstream airway cell signaling in response to the chronic PA infections observed in people with cystic fibrosis. To fill this gap in knowledge, the aim of this study was to establish an in vitro model that allows for PA infection of CF bronchial epithelial cells, cultured at the air liquid interface, for 24 hours. Our model shows with an inoculum of 2 x 102 CFUs of PA for 24 hours pro-inflammatory markers such as interleukin 6 and interleukin 8 are upregulated with little decrease in CF bronchial epithelial cell survival or monolayer confluency. Additionally, immunoblotting for phosphorylated phospholipase C gamma, a well-known downstream protein of fibroblast growth factor receptor signaling, showed significantly elevated levels after 24 hours with PA infection that were not seen at earlier timepoints. Finally, inhibition of phospholipase C shows significant downregulation of interleukin 8. Our data suggest that this newly developed in vitro "prolonged PA infection model" recapitulates the elevated inflammatory markers observed in CF, without compromising cell survival. This extended period of PA growth on CF bronchial epithelial cells will have impact on further studies of cell signaling and microbiological studies that were not possible in previous models using shorter PA exposures.

A policy analysis of how alkyl nitrites (poppers) became prescription-only in Aotearoa New Zealand.

BACKGROUND: Alkyl nitrites ('poppers') are a group of drugs that includes amyl nitrite, butyl nitrite, and isopropyl nitrite. Their use is prevalent among men who have sex with men (MSM), to enhance sexual comfort and pleasure. In Aotearoa New Zealand, all alkyl nitrites became prescription-only from March 2020. With alkyl nitrites no longer sold locally in stores, and no availability via pharmacies (even with a prescription), access has been significantly reduced. This decision was opposed by advocacy groups and people who use alkyl nitrites. This policy case study explores how this decision was made and impacts on MSM. METHODS: We use policy formation theory; both policy framing and Multiple Streams Framework, to analyse factors that contributed to this regulatory decision. Analysis of issue framing by policy coalitions was undertaken through review of documents including submissions and committee minutes. RESULTS: Two policy coalitions emerged, which differed in their issue framing. The Medicines Classification Committee conveyed concerns about evidence limitations, and recommended reclassification. NGOs and people who use alkyl nitrites communicated that there was no evidence of harm from alkyl nitrite use in New Zealand, and thus, given that there was evidence of benefit, the status quo should be maintained and further regulatory responses were unnecessary. Pre-existing processes created a situation where alkyl nitrite scheduling came unexpectedly onto the New Zealand policy agenda, and set the issue onto a somewhat pre-determined pathway with limited policy choices available. CONCLUSIONS: As a drug policy case study, it appears that reclassification was initiated due to a policy process that did not enable or support plausible alternatives. While the purpose of the reclassification was to improve safety, there was no evidence of harm prior to reclassification, and the reduction in access is likely to have increased harm for MSM.

Role of Epithelial-to-Mesenchymal Transition of Retinal Pigment Epithelial Cells in Glaucoma Cupping.

Optic nerve head (ONH) cupping is a clinical feature of glaucoma associated with extracellular matrix (ECM) remodelling and lamina cribrosa (LC) fibrosis. Peripapillary atrophy (PPA) occurs commonly in glaucoma, and is characterised by the loss of retinal pigment epithelium (RPE) adjacent to the ONH. Under pro-fibrotic conditions, epithelial cells throughout the body can differentiate into fibroblast-like cells through epithelial-to-mesenchymal transition (EMT) and contribute to ECM fibrosis. This is investigated here in the context of glaucoma and PPA. Human-donor ONH sections were assessed for the presence of the RPE cell-specific marker RPE65 using immunofluorescence. We examined the EMT response of ARPE-19 cells to the following glaucoma-related stimuli: cyclic mechanical stretch, mechanical stiffness, transforming growth factor beta (TGFß), and tumour necrosis factor alpha (TNFα). The gene expression was measured using the PCR of the epithelial tight junction marker zona occludens 1 (ZO-1) and the mesenchymal markers alpha smooth muscle actin (αSMA) and vimentin. A scratch assay was used to assess the ARPE-19 migration. Significant RPE-65 staining was demonstrated in the glaucomatous ONH. The cyclic stretching and substrate stiffness of the ARPE-19 cells caused a significant decrease in ZO-1 (p = 0.04), and an increase in αSMA (p = 0.04). The scratch assays demonstrated increased migration of ARPE19 in the presence of TNFα (p = 0.02). Furthermore, ARPE-19 cells undergo an EMT-like transition (gain of αSMA, loss of ZO-1 and increased migration) in response to glaucomatous stimuli. This suggests that during PPA, RPE cells have the potential to migrate into the ONH and differentiate into fibroblast-like cells, contributing to glaucomatous ONH cupping.

Impact of presentation at conference with timed release of academic publication.

Fast-tracking publication of original research to coincide with a conference presentation ("coordinated publication") is a mechanism of rapidly disseminating new data. How often this occurs, whether its frequency is changing, and the impact of this approach on information dissemination, is unknown. Our objective was to describe the characteristics of coordinated publications, how the practice has changed over time, and evaluate its potential impact on dissemination of study results. We conducted a cross-sectional study of randomized controlled trials published in NEJM, Lancet, and JAMA between January 1, 2015, and December 31, 2019. Among the 1533 included randomized controlled trials, 502 (33%) had coordinated publications. Coordinated publications increased from 30% [n = 94] in 2015 to 37% [n = 136] in 2019. Coordinated publications were more likely to be unblinded (61% [n = 305] vs. 52% [n = 532]) and more likely to be funded by industry (50% [n = 249] vs. 30% [n = 311]). The strongest predictor of a coordinated publication was cardiovascular disease subspecialty (OR = 3.96, 95% CI [2.95, 5.36]). The median number of citations (188 vs. 98) and the median Altmetric score (318 vs. 182) were higher for coordinated publications than non-coordinated publications. These differences persisted in a multivariable regression model. Coordinated publication is increasingly common. While coordinated publications may generate greater attention, they were observed to be more likely to be unblinded and more likely to be funded by industry, raising questions about the value and intentions of such promotion.

Analysis of recurrence in lung adenocarcinoma with spread through air spaces.

OBJECTIVES: Spread through air spaces is defined as tumor cells in air spaces away from the edge of tumor in lung carcinoma. It is associated with higher locoregional recurrence and lower survival in lung adenocarcinoma. The features of spread through air spaces portending worse outcomes are still under investigation. We reviewed our lung cancer experience to define potential factors related to spread through air spaces that influence recurrence and survival. METHODS: Between January 2010 and December 2017, we identified 968 patients who underwent resection for T1-3N0M0 lung adenocarcinoma. Of these, histologic examination was possible in 787 patients. We examined the presence of spread through air spaces, spread through air spaces characteristics (micropapillary, solid nest, or single cell), average density (number per slide), and farthest distance from tumor at which spread through air spaces was detected, or maximal spread distance. Overall survival and recurrence-free survival were estimated using Kaplan-Meier curves, and differences between spread through air spaces positive versus spread through air spaces negative groups were assessed using the log-rank test. RESULTS: Spread through air spaces was present in 389 of 787 of the reviewed cases (49.4%). Overall survival and recurrence-free survival were significantly lower in the spread through air spaces positive group over 10 years (P < .0001). The incidences of locoregional and distant recurrence were nearly doubled over 10 years in the spread through air spaces positive group compared with the spread through air spaces negative group (P = .002 and <.0001, respectively). In a multivariable Cox regression model adjusted for spread through air spaces characteristics, distance, and tumor size, lobar resection did not confer survival advantage in patients with spread through air spaces (hazard ratio of sublobar resection with respect to lobar resection, 1.44; 95% confidence interval, 0.98-2.11; P = .067). In the spread through air spaces positive group, spread through air spaces density was 2.7 ± 1.4 clusters per slide and the maximal spread distance was 2.2 ± 1.7 mm from the tumor edge. There was no observed correlation between spread through air spaces density or maximal spread distance and overall survival or recurrence. CONCLUSIONS: We show increased distant recurrence in spread through air spaces positive lung adenocarcinoma. Quantifiable measures of spread through air spaces do not appear to correlate with recurrence or survival metrics.

Meaninglessness and monotony in pandemic boredom.

Boredom is an affective experience that can involve pervasive feelings of meaninglessness, emptiness, restlessness, frustration, weariness and indifference, as well as the slowing down of time. An increasing focus of research in many disciplines, interest in boredom has been intensified by the recent Covid-19 pandemic, where social distancing measures have induced both a widespread loss of meaning and a significant disturbance of temporal experience. This article explores the philosophical significance of this aversive experience of 'pandemic boredom.' Using Heidegger's work as a unique vantage point, this article draws on survey data collected by researchers in an ongoing project titled 'Experiences of Social Distancing During the Covid-19 Pandemic' to give an original phenomenological interpretation of the meaninglessness and monotony of pandemic boredom. On a Heideggerian interpretation, pandemic boredom involves either a situative confrontation with relative meaninglessness that upholds our absorption in the everyday world, or an existential confrontation with absolute meaninglessness that forces us to take up the question of our existence. Arguing that boredom during the pandemic makes this distinction difficult to sustain, I consider some of the ways in which pandemic boredom might be seen to expose and then exceed the distinctive methodological limitations of Heidegger's philosophical interpretation of boredom.

Bleb Associated Xen Gel Stent Endophthalmitis: A Case Report and Review of Literature.

PURPOSE: To report a case of a unique late complication of the Xen gel stent, stent-related endophthalmitis was preceded by flattening of the bleb. CASE REPORT: A 63-year-old female was presented with late-onset endophthalmitis preceded by flattening of the bleb two years post-insertion of Xen gel stent. B-scan of the posterior chamber revealed vitritis and hyaloid condensation, with no viral, fungal, or bacterial pathologies identified on anterior chamber tap. The patient's eye responded to injections of intravitreal antibiotics. CONCLUSION: Endophthalmitis can occur as late as 2 years after implantation of glaucoma drainage device implants (GDIs) like the Xen gel stent if bleb flattening or leaking leads to contact of the stent with the conjunctiva. Therefore, in case of blebs getting flat, ophthalmologists should watch them more often. Intravitreal antibiotics may also be effective rather than surgical removal in the case of a non-eroded stent complicated by endophthalmitis.

The Depths of Temporal Desynchronization in Grief.

INTRODUCTION: The experience of disconnection is common in first-person accounts of grief. One way in which this feeling of estrangement can manifest is through the splintering apart of the time of the mourner and the time of the world. Supplementing and extending Thomas Fuchs' influential idea of temporal desynchronization, my aim in this article is to give an account of the heterogeneous ways in which grief can disturb time. METHOD: I organize these manifold experiences of temporal disruption according to a method of "depth analysis": a phenomenological interpretation of temporal desynchronization that tracks the increasing disconnect between the mourner and the world as it manifests in time. In so doing, I draw on a wide range of descriptive first-person responses to the question "Has your experience of time changed in any way?" - included as part of an online questionnaire on the emotional experience of grief conducted recently with colleagues at the University of York. I then stratify these according to a mild, moderate, and profound level of disruption. RESULTS: Before setting out the results of this analysis, I give a background account of Fuchs' interpretation of temporal desynchronization in phenomenological psychopathology more generally and in grief specifically. In my results, I then supplement and extend his interpretation by setting out my phenomenological depth analysis of the increasing disconnect between the time of the mourner and the time of the world, as demonstrated by the questionnaire data. As I argue, such a fine-grained account is an important step in understanding the way time can shape the meaning and significance of different grief experiences. Following this, in my discussion, I demonstrate how a depth approach might be helpful in differentiating between temporal disturbances in a range of affective disorders and give an illustrative comparison of grief and depression. CONCLUSION: In conclusion, I reflect briefly on what grief might reveal about the depth and complexity of temporal experience itself. In so doing, I consider how the radical disruptions to time in grief might transform the mourner's experience of time irreversibly but in a way that enables a renewed connection to both their deceased loved one and the world from which they have become estranged.