Search

PurposePseudomonas aeruginosa keratitis is a sight-threatening complication of contact lens wear, yet mechanisms by which lenses predispose to infection remain unclear. Here, we tested the hypothesis that tear fluid at the posterior contact lens surface can lose antimicrobial activity over time during lens wear.MethodsDaily disposable lenses were worn for 1, 2, 4, 6, or 8 hours immediately after removal from their packaging or after presoaking in sterile saline for 2 days to remove packaging solution. Unworn lenses were also tested, some coated in tears "aged" in vitro for 1 or 8 hours. Lenses were placed anterior surface down into tryptic soy agar cradles containing gentamicin (100 μg/mL) to kill bacteria already on the lens and posterior surfaces inoculated with gentamicin-resistant P. aeruginosa for 3 hours. Surviving bacteria were enumerated by viable counts of lens homogenates.ResultsPosterior surfaces of lenses worn by patients for 8 hours supported more P. aeruginosa growth than lenses worn for only 1 hour, if lenses were presoaked before wear (∼ 2.4-fold, p = 0.01). This increase was offset if lenses were not presoaked to remove packaging solution (p = 0.04 at 2 and 4 hours). Irrespective of presoaking, lenses worn for 8 hours showed more growth on their posterior surface than unworn lenses coated with tear fluid that was aged for 8 hours in vitro (∼ 8.6-fold, presoaked, p = 0.003; ∼ 5.4-fold from packaging solution, p = 0.004). Indeed, in vitro incubation did not impact tear antimicrobial activity.ConclusionsThis study shows that postlens tear fluid can lose antimicrobial activity over time during contact lens wear, supporting the idea that efficient tear exchange under a lens is critical for homeostasis. Additional studies are needed to determine applicability to other lens types, wearing modalities, and relevance to contact lens-related infections.

Pseudomonas aeruginosa is invasive or cytotoxic to host cells, depending on the type III secretion system (T3SS) effectors encoded. While the T3SS is known to be involved in disease in vivo, how it participates remains to be clarified. Here, mouse models of superficial epithelial injury (tissue paper blotting with EGTA treatment) and immunocompromise (MyD88 deficiency) were used to study the contribution of the T3SS transcriptional activator ExsA to epithelial traversal. Corneas of excised eyeballs were inoculated with green fluorescent protein (GFP)-expressing PAO1 or isogenic exsA mutants for 6 h ex vivo before bacterial traversal and epithelial thickness were quantified by using imaging. In the blotting-EGTA model, exsA mutants were defective in capacity for traversal. Accordingly, an ∼16-fold variability in exsA expression among PAO1 isolates from three sources correlated with epithelial loss. In contrast, MyD88-/- epithelia remained susceptible to P. aeruginosa traversal despite exsA mutation. Epithelial lysates from MyD88-/- mice had reduced antimicrobial activity compared to those from wild-type mice with and without prior antigen challenge, particularly 30- to 100-kDa fractions, for which mass spectrometry revealed multiple differences, including (i) lower baseline levels of histones, tubulin, and lumican and (ii) reduced glutathione S-transferase, annexin, and dermatopontin, after antigen challenge. Thus, the importance of ExsA in epithelial traversal by invasive P. aeruginosa depends on the compromise enabling susceptibility, suggesting that strategies for preventing infection will need to extend beyond targeting the T3SS. The data also highlight the importance of mimicking conditions allowing susceptibility in animal models and the need to monitor variability among bacterial isolates from different sources, even for the same strain.

This paper aims to highlight the significant role of culture in human responses to global environmental challenges. Specifically, it discusses three thematic clusters of research, which demonstrate that: (i) culture can influence pro-environmental behavior through shaping values and moderating the relationship between psychological determinants and such behavior; (ii) perceptions of nature and its relationships with humans vary across cultures; and (iii) consumption behaviors are often shaped by practices that constitute social life within communities. Evidence from these research clusters suggests that understanding cultural dynamics is essential for designing effective, context-sensitive interventions aimed at driving sustainability transitions. Future research should further explore the interplay between cultural and non-cultural contextual factors and consider the perspectives of underrepresented regions., Competing Interests: Declaration of competing interest The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: Although natural hazards (e.g., tropical cyclones, earthquakes) disproportionately affect developing countries, most research on their mental health impact has been conducted in high-income countries. We aimed to summarize prevalences of mental disorders in Global South populations (classified according to the United Nations Human Development Index) affected by natural hazards., Methods: To identify eligible studies for this meta-analysis, we searched MEDLINE, PsycINFO and Web of Science up to February 13, 2024, for observational studies with a cross-sectional or longitudinal design that reported on at least 100 adult survivors of natural hazards in a Global South population and assessed mental disorders with a validated instrument at least 1 month after onset of the hazard. Main outcomes were the short- and long-term prevalence estimates of mental disorders. The project was registered on the International Prospective Register of Systematic Reviews (CRD42023396622)., Results: We included 77 reports of 75 cross-sectional studies (six included a non-exposed control group) comprising 82,400 individuals. We found high prevalence estimates for post-traumatic stress disorder (PTSD) in the general population (26.0% [95% CI 18.5-36.3]; I 2 = 99.0%) and depression (21.7% [95% CI 10.5-39.6]; I 2 = 99.2%) during the first year following the event, with similar prevalences observed thereafter (i.e., 26.0% and 23.4%, respectively). Results were similar for regions with vs. without recent armed conflict. In displaced samples, the estimated prevalence for PTSD was 46.5% (95% CI 39.0-54.2; k = 6; I 2 = 93.3). We furthermore found higher symptom severity in exposed, versus unexposed, individuals. Data on other disorders were scarce, apart from short-term prevalence estimates of generalised anxiety disorder (15.9% [95% CI 4.7-42.0]; I 2 = 99.4)., Conclusions: Global South populations exposed to natural hazards report a substantial burden of mental disease. These findings require further attention and action in terms of implementation of mental health policies and low-threshold interventions in the Global South in the aftermath of natural hazards. However, to accurately quantify the true extent of this public health challenge, we need more rigorous, well-designed epidemiological studies across diverse regions. This will enable informed decision making and resource allocation for those in need.

People may experience anxiety and related distress when they come in contact with climate change (i.e., climate change anxiety). Climate change anxiety can be conceptualized as either emotional-based response (the experience of anxiety-related emotions) or impairment-based response (the experience of impairment in daily functioning). To date, it remains uncertain how these distinct manifestations of climate change anxiety are related. Conceptually, the experience of climate change anxiety may transform from an adaptive and healthy emotional response to an impairment in daily functioning. We conducted two two-wave longitudinal studies to examine the possible bidirectional relationships between three manifestations of climate change anxiety. We recruited 942 adults (mean age = 43.1) and 683 parents (mean age = 46.2) in Studies 1 and 2, respectively. We found that Time 1 emotion-based response was positively linked to Time 2 cognitive-emotional impairment, while Time 1 cognitive-emotional impairment was positively related to Time 2 functional impairment. In Study 2, we also found a bidirectional positive relationship between generalized anxiety and emotion-based climate change anxiety over time. Overall, our findings provide initial support to the temporal relationships between different manifestations of climate change anxiety, corroborating that climate change anxiety may develop from emotional responses to impairment in functioning., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Epstein-Barr virus (EBV) manipulates the ubiquitin-proteasome system and regulators of Bcl-2 family to enable the persistence of the virus and survival of the host cells through the expression of viral proteins in distinct latency patterns. We postulate that the combination of bortezomib (proteasome inhibitor) and venetoclax (Bcl-2 inhibitor) [bort/venetoclax] will cause synergistic killing of post-transplant lymphoproliferative disorder (PTLD) through targeting the pro-survival function of latent viral proteins such as latent membrane protein-1 (LMP-1) and EBV nuclear antigen-3C (EBNA-3C). Bort/venetoclax could synergistically kill spontaneous lymphoblastoid cell lines (sLCLs) derived from patients with PTLD and EBV-associated hemophagocytic lymphohistiocytosis by inducing DNA damage response, apoptosis and G1-S cell cycle arrest in a ROS-dependent manner. Bortezomib potently induced the expression of Noxa, a pro-apoptotic initiator and when combined with venetoclax, inhibited Mcl-1 and Bcl-2 simultaneously. Bortezomib prevented LMP-1 induced proteasomal degradation of IκBα leading to the suppression of the NF-κB signaling pathway. Bortezomib also rescued Bcl-6 from EBNA-3C mediated proteasomal degradation thus maintaining the repression of cyclin D1 and Bcl-2 causing G1-S arrest and apoptosis. Concurrently, venetoclax inhibited Bcl-2 upregulated by either LMP-1 or EBNA-3C. Bort/venetoclax decreased the expression of phosphorylated p65 and Bcl-2 at serine 70 thereby suppressing the NF-κB signaling pathway and promoting apoptosis, respectively. These data corroborated the marked suppression of the growth of xenograft of sLCL in SCID mice (p<0.001). Taken together, the combination of bortezomib and venetoclax targets the pro-survival function of LMP-1 and EBNA-3C of Epstein-Barr virus in spontaneous lymphoblastoid cell lines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Global issues such as environmental problems and climate change, require collective efforts. Global identity has been linked to the promotion of pro-environmental behavior by international and environmental organizations. In environment-related research, this all-inclusive social identity has been consistently related to pro-environmental behavior and environmental concern, but the underlying mechanisms are not well understood. This current systematic review seeks to examine past studies across disciplines that have reported findings on the relationship between global identity and the constructs of pro-environmental behavior and environmental concern and to synthesize findings on the potential pathways behind this relationship. Thirty articles were identified through a systematic search. We found that most studies reported a positive correlation, and the effect of global identity on pro-environmental behavior and environmental concern was stable across studies. Only nine of the studies empirically examined the underlying mechanisms of this relationship. Three major themes of these underlying mechanisms emerged: obligation, responsibility, and relevance. These mediators highlight the role of global identity in pro-environmental behavior and environmental concern via how individuals relate to other humans and how they appraise environmental problems. We also observed a heterogeneity in measurements of global identity and environment-related outcomes. As a topic of interest in multiple disciplines, a variety of global identity labels have been adopted, such as global identity, global social identity, humanity identity, Identification With All Humanity, global/world citizen, connectedness to humanity, global belonging, and psychological sense of global community. Self-report measures of behavior were common, but observations of actual behavior were rare. Knowledge gaps are identified, and future directions are suggested., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pong and Tam.)

Large populations worldwide have been deprived from nature experiences due to mass quarantines and lockdowns during the COVID-19 pandemic, and face a looming mental health crisis. Virtual reality offers a safe and practical solution to increase nature exposure. This research examined the effects of virtual nature using a within-subject design with young adults (Study 1) and senior citizens (Study 2). Results from the young adult sample showed that walking in a virtual forest reduced negative affect due to enhanced nature connectedness, and reduced stress measured by heart rate. Consistently, the senior citizen sample reported improved positive affect due to enhanced nature connectedness after the virtual nature walk. Our findings unveil the underlying mechanism of how virtual nature may improve psychological well-being and demonstrated how virtual nature can be used as an intervention to promote mental health., Supplementary Information: The online version contains supplementary material available at 10.1007/s10055-021-00604-4., Competing Interests: Conflict of interestAll authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature 2021.)

Competing Interests: The authors have no conflict of interest to declare.

Epstein-Barr virus (EBV) is strongly associated with a spectrum of EBV-associated lymphoproliferative diseases (EBV-LPDs) ranging from post-transplant lymphoproliferative disorder, B cell lymphomas (e.g., endemic Burkitt lymphoma, Hodgkin lymphoma, and diffuse large B cell lymphoma) to NK or T cell lymphoma (e.g., nasal NK/T-cell lymphoma). The virus expresses a number of latent viral proteins which are able to manipulate cell cycle and cell death processes to promote survival of the tumor cells. Several FDA-approved drugs or novel compounds have been shown to induce killing of some of the EBV-LPDs by inhibiting the function of latent viral proteins or activating the viral lytic cycle from latency. Here, we aim to provide an overview on the mechanisms by which EBV employs to drive the pathogenesis of various EBV-LPDs and to maintain the survival of the tumor cells followed by a discussion on the development of viral-targeted strategies based on the understanding of the patho-mechanisms.

Combination of suberoylanilide hydroxamic acid (SAHA) and bortezomib (SAHA/bortezomib) was shown to synergistically induce killing of lymphoblastoid cell lines (LCL) and Burkitt lymphoma (BL) of type III or Wp-restricted latency, both of which express EBNA3A, -3B and -3C proteins. We hypothesize that SAHA/bortezomib can counteract the survival functions conferred by the EBNA3 proteins. We tested the effect of SAHA/bortezomib on the survival of BL cell lines containing EBNA3A, -3B or -3C knockout EBV with or without the respective revertant EBNA3 genes. Isobologram analysis showed that SAHA/bortezomib induced significantly greater synergistic killing of EBNA3C-revertant cells when compared with EBNA3C-knockout cells. Such differential response was not observed in either EBNA3A or -3B revertant versus their knockout pairs. Interestingly, EBNA3C-knockout cells showed significant G2/M arrest whilst EBNA3C-revertant cells and LCLs escaped G2/M arrest induced by SAHA/bortezomib and became more susceptible to the induction of apoptosis. In parallel, SAHA/bortezomib induced stronger expression of p21 WAF1 but weaker expression of p-cdc25c, an M-phase inducer phosphatase, in EBNA3C-expressing cells when compared with EBNA3C-knockout cells. SAHA/bortezomib also induced greater growth suppression of EBNA3C-expressing xenografts (EBNA3C-revertant and LCL) than that of EBNA3C-knockout xenografts in SCID mice. In conclusion, our data showed that SAHA/bortezomib could synergistically induce killing of BL and LCL through counteracting the survival functions of EBNA3C, providing a strong basis for clinical testing of this drug combination in patients with EBV-associated lymphoproliferative diseases., Competing Interests: CONFLICTS OF INTEREST The authors disclosed no potential conflicts of interest.

Epstein-Barr virus (EBV) is closely associated with several lymphomas (endemic Burkitt lymphoma, Hodgkin lymphoma and nasal NK/T-cell lymphoma) and epithelial cancers (nasopharyngeal carcinoma and gastric carcinoma). To maintain its persistence in the host cells, the virus manipulates the ubiquitin-proteasome system to regulate viral lytic reactivation, modify cell cycle checkpoints, prevent apoptosis and evade immune surveillance. In this review, we aim to provide an overview of the mechanisms by which the virus manipulates the ubiquitin-proteasome system in EBV-associated lymphoid and epithelial malignancies, to evaluate the efficacy of proteasome inhibitors on the treatment of these cancers and discuss potential novel viral-targeted treatment strategies against the EBV-associated cancers., Competing Interests: The authors declare no conflict of interest.

The purpose of this study was to investigate whether myofibroblast-related fibrosis (scarring) after microbial keratitis was modulated by the epithelial basement membrane (EBM) injury and regeneration. Rabbits were infected with Pseudomonas aeruginosa after epithelial scrape injury and the resultant severe keratitis was treated with topical tobramycin. Corneas were analyzed from one to four months after keratitis with slit lamp photos, immunohistochemistry for alpha-smooth muscle actin (α-SMA) and monocyte lineage marker CD11b, and transmission electron microscopy. At one month after keratitis, corneas had no detectible EBM lamina lucida or lamina densa, and the central stroma was packed with myofibroblasts that in some eyes extended to the posterior corneal surface with damage to Descemet's membrane and the endothelium. At one month, a nest of stromal cells in the midst of the SMA + myofibroblasts in the stroma that were CD11b+ may be fibrocyte precursors to myofibroblasts. At two to four months after keratitis, the EBM fully-regenerated and myofibroblasts disappeared from the anterior 60-90% of the stroma of all corneas, except for one four-month post-keratitis cornea where anterior myofibroblasts were still present in one localized pocket in the cornea. The organization of the stromal extracellular matrix also became less disorganized from two to four months after keratitis but remained abnormal compared to controls at the last time point. Myofibroblasts persisted in the posterior 10%-20% of posterior stroma even at four months after keratitis in the central cornea where Descemet's membrane and the endothelium were damaged. This study suggests that the EBM has a critical role in modulating myofibroblast development and fibrosis after keratitis-similar to the role of EBM in fibrosis after photorefractive keratectomy. Damage to EBM likely allows epithelium-derived transforming growth factor beta (TGFβ) to penetrate the stroma and drive development and persistence of myofibroblasts. Eventual repair of EBM leads to myofibroblast apoptosis when the cells are deprived of requisite TGFβ to maintain viability. The endothelium and Descemet's membrane may serve a similar function modulating TGFβ penetration into the posterior stroma-with the source of TGFβ likely being the aqueous humor., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Prior studies on value development across adulthood have generally shown that as people age, they espouse communal values more strongly and agentic values less strongly. Two studies investigated whether these age differences in personal values might differ according to cultural values. Study 1 examined whether these age differences in personal values, and their associations with subjective well-being, showed the same pattern across countries that differed in individualism-collectivism. Study 2 compared age differences in personal values in the Canadian culture that emphasized agentic values more and the Chinese culture that emphasized communal values more. Personal and cultural values of each individual were directly measured, and their congruence were calculated and compared across age and cultures. Findings revealed that across cultures, older people had lower endorsement of agentic personal values and higher endorsement of communal personal values than did younger people. These age differences, and their associations with subjective well-being, were generally not influenced by cultural values. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Anthropomorphic persuasive appeals are prevalent. However, their effectiveness has not been well studied. The present research addresses this issue with two experiments in the context of environmental persuasion. It shows that anthropomorphic messages, relative to non-anthropomorphic ones, appear to motivate more conservation behaviour and elicit more favourable message responses only among recipients who have a strong need for effectance or social connection. Among recipients whose such need is weak, anthropomorphic appeals seem to backfire. These findings extend the research on motivation and persuasion and add evidence to the motivational bases of anthropomorphism. In addition, joining some recent studies, the present research highlights the implications of anthropomorphism of nature for environmental conservation efforts, and offers some practical suggestions for environmental persuasion., (© 2014 The British Psychological Society.)