Hydrostatic pressure does not cause detectable changes to survival of human retinal ganglion

Purpose: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. One consequence of raised IOP is that ocular tissues are subjected to increased hydrostatic pressure (HP). The effect of raised HP on stress pathway signaling and retinal ganglion cell (RGC) survival in the human retina was investigated. Methods: A chamber was designed to expose cells to increased HP (constant and fluctuating). Accurate pressure control (10-100mmHg) was achieved using mass flow controllers. Human organotypic retinal cultures (HORCs) from donor eyes (<24h post mortem) were cultured in serum-free DMEM/HamF12. Increased HP was compared to simulated ischemia (oxygen glucose deprivation, OGD). Cell death and apoptosis were measured by LDH and TUNEL assays, RGC marker expression by qRT-PCR (THY-1) and RGC number by immunohistochemistry (NeuN). Activated p38 and JNK were detected by Western blot. Results: Exposure of HORCs to constant (60mmHg) or fluctuating (10-100mmHg; 1 cycle/min) pressure for 24 or 48h caused no loss of structural integrity, LDH release, decrease in RGC marker expression (THY-1) or loss of RGCs compared with controls. In addition, there was no increase in TUNEL-positive NeuN-labelled cells at either time-point indicating no increase in apoptosis of RGCs. OGD increased apoptosis, reduced RGC marker expression and RGC number and caused elevated LDH release at 24h. p38 and JNK phosphorylation remained unchanged in HORCs exposed to fluctuating pressure (10-100mmHg; 1 cycle/min) for 15, 30, 60 and 90min durations, whereas OGD (3h) increased activation of p38 and JNK, remaining elevated for 90min post-OGD. Conclusions: Directly applied HP had no detectable impact on RGC survival and stress-signalling in HORCs. Simulated ischemia, however, activated stress pathways and caused RGC death. These results show that direct HP does not cause degeneration of RGCs in the ex vivo human retina

Essentials in Accident and Emergency Medicine Radiation Injury: Response and Treatment

The discovery of radiation has enabled great healthcare advances as well as catastrophic injury. This paper reviews major historical incidents of public radiation exposure and the evolution of standards affecting today’s public and health care workers. Current patient care and response assessment to radiation exposure are reviewed. The strengths of modern radiation therapy and the need for continuous process improvements to ensure optimal patient care and secure safe environments are identified. The discovery of radiation has brought significant scientific achievements as well as catastrophic injury

A Longitudinal Analysis of Violence and Housing Insecurity

Violence and housing insecurity are horrible events that may be intertwined, with violence possibly forcing victims to abandon their accommodations and housing insecurity depriving people of the safety of a home or placing them in compromised circumstances. This study uses national, prospective, longitudinal data from the Journeys Home Survey to examine how violence, housing insecurity, and other characteristics in one period affect disadvantaged Australian men's and women's chances of experiencing violence and housing insecurity in subsequent periods. The study is one of the first to investigate these relationships prospectively and unusual in considering how violence among adult men contributes to their housing insecurity. We estimate dynamic multivariate models that control for observed and time-invariant unobserved characteristics and find that men's chances of being housing secure without experiencing violence are 24-45 percent lower and women's chances are 12- 20 percent lower if they experienced housing insecurity, violence or both in the previous period. Heavy drinking, marijuana use, psychological distress, and a history of childhood abuse and neglect also increase the risks of violence and housing insecurity for both genders, while the presence of children reduces these risks. Women who are bisexual or lesbian and women with homeless friends also face elevated risks of housing insecurity, while men's sexual orientation and friend networks seem less relevant

The effectiveness of health appraisal processes currently in addressing health and wellbeing during spatial plan appraisal: a systematic review

<p>Abstract</p> <p>Background</p> <p>Spatial planning affects the built environment, which in turn has the potential to have a significant impact on health, for good or ill. One way of ensuring that spatial plans take due account of health is through the inclusion of health considerations in the statutory and non statutory appraisal processes linked to plan-making processes.</p> <p>Methods</p> <p>A systematic review to identify evaluation studies of appraisals or assessments of plans where health issues were considered from 1987 to 2010.</p> <p>Results</p> <p>A total of 6161 citations were identified: 6069 from electronic databases, 57 fromwebsite searches, with a further 35 citations from grey literature, of which 20 met the inclusion criteria. These 20 citations reported on a total of 135 different case studies: 11 UK HIA; 11 non UK high income countries HIA, 5 UK SEA or other integrated appraisal; 108 non UK high income SEA or other integrated appraisal. All studies were in English. No relevant studies were identified reporting on low or middle income countries.</p> <p>The studies were limited by potential bias (no independent evaluation, with those undertaking the appraisal also responsible for reporting outcomes), lack of detail and a lack of triangulation of results. Health impact assessments generally covered the four specified health domains (physical activity, mental health and wellbeing, environmental health issues such as pollution and noise, injury) more comprehensively than SEA or other integrated appraisals, although mental health and wellbeing was an underdeveloped area. There was no evidence available on the incorporation of health in Sustainability Appraisal, limited evidence that the recommendations from any type of appraisal were implemented, and almost no evidence that the recommendations had led to the anticipated outcomes or improvements in health postulated.</p> <p>Conclusion</p> <p>Research is needed to assess (i) the degree to which statutory plan appraisal processes (SA in the UK) incorporate health; (ii) whether recommendations arising from health appraisal translate into the development process and (iii) whether outcomes are as anticipated.</p

Longitudinal In Vivo Imaging of Retinal Ganglion Cells and Retinal Thickness Changes Following Optic Nerve Injury in Mice

Retinal ganglion cells (RGCs) die in sight-threatening eye diseases. Imaging RGCs in humans is not currently possible and proof of principle in experimental models is fundamental for future development. Our objective was to quantify RGC density and retinal thickness following optic nerve transection in transgenic mice expressing cyan fluorescent protein (CFP) under control of the Thy1 promoter, expressed by RGCs and other neurons.A modified confocal scanning laser ophthalmoscopy (CSLO)/spectral-domain optical coherence tomography (SD-OCT) camera was used to image and quantify CFP+ cells in mice from the B6.Cg-Tg(Thy1-CFP)23Jrs/J line. SD-OCT circle (1 B-scan), raster (37 B-scans) and radial (24 B-scans) scans of the retina were also obtained. CSLO was performed at baseline (n = 11) and 3 (n = 11), 5 (n = 4), 7 (n = 10), 10 (n = 6), 14 (n = 7) and 21 (n = 5) days post-transection, while SD-OCT was performed at baseline and 7, 14 and 35 days (n = 9) post-transection. Longitudinal change in CFP+ cell density and retinal thickness were computed. Compared to baseline, the mean (SD) percentage CFP+ cells remaining at 3, 5, 7, 10, 14 and 21 days post-transection was 86 (9)%, 63 (11)%, 45 (11)%, 31 (9)%, 20 (9)% and 8 (4)%, respectively. Compared to baseline, the mean (SD) retinal thickness at 7 days post-transection was 97 (3)%, 98 (2)% and 97 (4)% for the circle, raster and radial scans, respectively. The corresponding figures at 14 and 35 days post-transection were 96 (3)%, 97 (2)% and 95 (3)%; and 93 (3)%, 94 (3)% and 92 (3)%.Longitudinal imaging showed an exponential decline in CFP+ cell density and a small (≤8%) reduction in SD-OCT measured retinal thickness post-transection. SD-OCT is a promising tool for detecting structural changes in experimental optic neuropathy. These results represent an important step towards translation for clinical use

CXCR3 Antagonism of SDF-1(5-67) Restores Trabecular Function and Prevents Retinal Neurodegeneration in a Rat Model of Ocular Hypertension

Glaucoma, the most common cause of irreversible blindness, is a neuropathy commonly initiated by pathological ocular hypertension due to unknown mechanisms of trabecular meshwork degeneration. Current antiglaucoma therapy does not target the causal trabecular pathology, which may explain why treatment failure is often observed. Here we show that the chemokine CXCL12, its truncated form SDF-1(5-67), and the receptors CXCR4 and CXCR3 are expressed in human glaucomatous trabecular tissue and a human trabecular cell line. SDF-1(5-67) is produced under the control of matrix metallo-proteinases, TNF-α, and TGF-β2, factors known to be involved in glaucoma. CXCL12 protects in vitro trabecular cells from apoptotic death via CXCR4 whereas SDF-1(5-67) induces apoptosis through CXCR3 and caspase activation. Ocular administration of SDF-1(5-67) in the rat increases intraocular pressure. In contrast, administration of a selective CXCR3 antagonist in a rat model of ocular hypertension decreases intraocular pressure, prevents retinal neurodegeneration, and preserves visual function. The protective effect of CXCR3 antagonism is related to restoration of the trabecular function. These data demonstrate that proteolytic cleavage of CXCL12 is involved in trabecular pathophysiology, and that local administration of a selective CXCR3 antagonist may be a beneficial therapeutic strategy for treating ocular hypertension and subsequent retinal degeneration