A comparison of reading, in people with simulated and actual central vision loss, with static text, horizontally scrolling text, and rapid serial visual presentation

Reading with central vision loss (CVL), as caused by macular disease, may be enhanced by presenting text using dynamic formats such as horizontally scrolling text or rapid serial visual presentation (RSVP). The rationale for these dynamic text formats is that they can be read while holding gaze away from the text, potentially supporting reading while using the eccentric viewing strategy. This study was designed to evaluate the practice of reading with CVL, with passages of text presented as static sentences, with horizontal scrolling sentences, or as single-word RSVP. In separate studies, normally sighted participants with a simulated (artificial) central scotoma, controlled by an eye-tracker, or participants with CVL resulting from macular degeneration read passages of text using the eccentric viewing technique. Comprehension was better overall with scrolling text when reading with a simulated CVL, whereas RSVP produced lower overall comprehension and high error rates. Analysis of eye movement behavior showed that participants consistently adopted a strategy of making multiple horizontal saccades on the text itself. Adherence to using eccentric viewing was better with RSVP, but this did not translate into better reading performance. Participants with macular degeneration and an actual CVL also showed the highest comprehension and lowest error rates with scrolling text and the lowest comprehension and highest errors with RSVP. We conclude that scrolling text can support effective reading in people with CVL and has potential as a reading aid

Cardiac thromboxane A2 receptor activation does not directly induce cardiomyocyte hypertrophy but does cause cell death that is prevented with gentamicin and 2-APB

Abstract Background We have previously shown that the thromboxane (TXA2) receptor agonist, U46619, can directly induce ventricular arrhythmias that were associated with increases in intracellular calcium in cardiomyocytes. Since TXA2 is an inflammatory mediator and induces direct calcium changes in cardiomyocytes, we hypothesized that TXA2 released during ischemia or inflammation could also cause cardiac remodeling. Methods U46619 (0.1-10 μM) was applied to isolated adult mouse ventricular primary cardiomyocytes, mouse ventricular cardiac muscle strips, and cultured HL-1 cardiomyocytes and markers of hypertrophy and cell death were measured. Results We found that TXA2 receptors were expressed in ventricular cardiomyocytes and were functional via calcium imaging. U46619 treatment for 24 h did not increase expression of pathological hypertrophy genes (atrial natriuretic peptide, β-myosin heavy chain, skeletal muscle α-actin) and it did not increase protein synthesis. There was also no increase in cardiomyocyte size after 48 h treatment with U46619 as measured by flow cytometry. However, U46619 (0.1-10 μM) caused a concentration-dependent increase in cardiomyocyte death (trypan blue, MTT assays, visual cell counts and TUNEL stain) after 24 h. Treatment of cells with the TXA2 receptor antagonist SQ29548 and inhibitors of the IP3 pathway, gentamicin and 2-APB, eliminated the increase in cell death induced by U46619. Conclusions Our data suggests that TXA2 does not induce cardiac hypertrophy, but does induce cell death that is mediated in part by IP3 signaling pathways. These findings may provide important therapeutic targets for inflammatory-induced cardiac apoptosis that can lead to heart failure.Peer Reviewe

Following the status of visual cortex over time in patients with macular degeneration reveals atrophy of visually deprived brain regions

Purpose: Previous research has shown atrophy of visual cortex can occur in retinotopic representations of retinal lesions resulting from eye disease. However, the time course of atrophy cannot be established from these cross-sectional studies, which included patients with long-standing disease of varying severity. Our aim therefore was to measure visual cortical structure over time in participants after onset of unilateral visual loss resulting from age-related macular degeneration (AMD). Methods: Inclusion criteria were onset of acute unilateral neovascular AMD with bilateral dry-AMD based on clinical examination. Therefore, substantial loss of unilateral visual input to cortex was relatively well-defined in time. Changes in cortical anatomy were assessed in the occipital lobe as a whole, and in cortical representations of the lesion and intact retina, the lesion and intact projection zones, respectively. Whole brain, T1-weighted MRI was taken at diagnosis (before anti-angiogenic treatment to stabilise the retina), during the 3-4-month initial treatment period, with a long-term follow-up ~5 (range 3.8 – 6.1 years) years later. Results: Significant cortical atrophy was detected at long-term follow-up only, with a reduction in mean cortical volume across the whole occipital lobe. Importantly, this reduction was explained by cortical thinning of the lesion projection zone, which suggests additional changes to those associated with normal ageing. Over the period of study, anti-angiogenic treatment stabilised visual acuity and central retinal thickness, suggesting that the atrophy detected was most likely governed by long-term decreased visual input. Conclusions: Our results indicate that consequences of eye disease on visual cortex are atrophic and retinotopic. Our work also raises the potential to follow the status of visual cortex in individuals over time to inform on how best to treat patients, particularly with restorative techniques

The development of novel LTA4H modulators to selectively target LTB4 generation

The pro-inflammatory mediator leukotriene B4 (LTB4) is implicated in the pathologies of an array of diseases and thus represents an attractive therapeutic target. The enzyme leukotriene A4 hydrolase (LTA4H) catalyses the distal step in LTB4 synthesis and hence inhibitors of this enzyme have been actively pursued. Despite potent LTA4H inhibitors entering clinical trials all have failed to show efficacy. We recently identified a secondary anti-inflammatory role for LTA4H in degrading the neutrophil chemoattractant Pro-Gly-Pro (PGP) and rationalized that the failure of conventional LTA4H inhibitors may be that they inadvertently prevented PGP degradation. We demonstrate that these inhibitors do indeed fail to discriminate between the dual activities of LTA4H, and enable PGP accumulation in mice. Accordingly, we have developed novel compounds that potently inhibit LTB4 generation whilst leaving PGP degradation unperturbed. These novel compounds could represent a safer and superior class of LTA4H inhibitors for translation into the clinic

Neutrophils restrain allergic airway inflammation by limiting ILC2 function and monocyte-dendritic cell antigen presentation

Neutrophil mobilization, recruitment, and clearance must be tightly regulated as overexuberant neutrophilic inflammation is implicated in the pathology of chronic diseases, including asthma. Efforts to target neutrophils therapeutically have failed to consider their pleiotropic functions and the implications of disrupting fundamental regulatory pathways that govern their turnover during homeostasis and inflammation. Using the house dust mite (HDM) model of allergic airway disease, we demonstrate that neutrophil depletion unexpectedly resulted in exacerbated T helper 2 (T 2) inflammation, epithelial remodeling, and airway resistance. Mechanistically, this was attributable to a marked increase in systemic granulocyte colony-stimulating factor (G-CSF) concentrations, which are ordinarily negatively regulated in the periphery by transmigrated lung neutrophils. Intriguingly, we found that increased G-CSF augmented allergic sensitization in HDM-exposed animals by directly acting on airway type 2 innate lymphoid cells (ILC2s) to elicit cytokine production. Moreover, increased systemic G-CSF promoted expansion of bone marrow monocyte progenitor populations, which resulted in enhanced antigen presentation by an augmented peripheral monocyte-derived dendritic cell pool. By modeling the effects of neutrophil depletion, our studies have uncovered previously unappreciated roles for G-CSF in modulating ILC2 function and antigen presentation. More broadly, they highlight an unexpected regulatory role for neutrophils in limiting T 2 allergic airway inflammation

Art therapy with refugee children: a qualitative study explored through the lens of art therapists and their experiences

This is an Accepted Manuscript of an article published by Taylor & Francis in International Journal of Art Therapy on 9-11-2018, available online: https://doi.org/10.1080/17454832.2018.1533571This article sets out to explore the use of art therapy with refugee children, from the perspective of art therapists and their experiences. Three semi-structured interviews were conducted to gain insights by capturing experiences and stories. Using thematic analysis, five themes were identified: (1) giving voice; (2) rebuilding trust, opening wounds; (3) sharing stories, healing pain; (4) exploring identity, discovering new-self; and (5) understanding art therapy. Upon reflection, two key aspects of art therapy were established, these were identified as: (1) providing refugee children with a safe space to heal and discover new-self, and (2) giving refugee children a voice to express and share stories. Despite the last of the five themes (understanding art therapy) being established as a factor that limits the use of art therapy, this has created an avenue for further research. From the findings, it was concluded that art therapy can be a useful form of psychotherapy for refugee children. Art therapy can provide these children with a safe space to heal, and give them a voice to be heard

OCCURRENCE OF THE FALCATED TEAL ANAS-FALCATA GEORGI IN KHIJADIA BIRD SANCTUARY GUJARAT INDIA

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