The effects of severe myopia on the properties of sampling units in peripheral retina

Significance: Poor peripheral visual acuity in myopia may reflect, in part, photoreceptor misalignment with the exit pupil of the eye. We speculate that if such misalignment causes sufficient visual deprivation and/or disrupts retinal feedback processes, it may influence eye growth itself. Purpose: It is known that myopic eyes have a reduced peripheral resolution acuity relative to emmetropic eyes, though it remains unclear how mechanical stretching of the retina in myopia impacts on peripheral visual performance. Our aim was to determine how retinal stretching affects the properties of sampling units in peripheral vision. Methods: Three-dimensional magnetic resonance imaging provided a depiction in vivo of ocular shape, allowing the inter-eye ratio of retinal image surface areas and the relative alignment of surfaces to be determined in our observer, who was unique in having severe myopia in the right eye (~21D) but only modest myopia in the left (~3D). Visual performance was assessed for the detection and direction discrimination of drifting sinusoids positioned 40º in the temporal retina. Applying the sampling theorem to our measures, we estimated the density and cut-off frequency of the underlying sampling units. Results: The retinal image surface area of the right eye was 40% larger than that of the left, and was rotated 8.9º anticlockwise relative to the left eye’s image surface. In agreement with a linear stretch model of myopia, the sampling density of the right eye was reduced by approximately the same ratio as that predicted from the inter-eye MRI data, namely 1.18. However, the cut-off frequency (cycles/mm) of the right eye was approximately half that of the left, a reduction that cannot be explained solely by a linear areal expansion of retinal sampling units. Conclusions: Poor peripheral acuity in severe myopia may be caused, at least in part, by receptoral misalignment with the exit pupil

The UK Burden of Injury Study - a protocol

Background Globally and nationally large numbers of people are injured each year, yet there is little information on the impact of these injuries on people's lives, on society and on health and social care services. Measurement of the burden of injuries is needed at a global, national and regional level to be able to inform injured people of the likely duration of impairment; to guide policy makers in investing in preventative measures; to facilitate the evaluation and cost effectiveness of interventions and to contribute to international efforts to more accurately assess the global burden of injuries. Methods/Design A prospective, longitudinal multi-centre study of 1333 injured individuals, atttending Emergency Departments or admitted to hospital in four UK areas: Swansea, Surrey, Bristol and Nottingham. Specified quotas of patients with defined injuries covering the whole spectrum will be recruited. Participants (or a proxy) will complete a baseline questionnaire regarding their injury and pre-injury quality of life. Follow up occurs at 1, 4, and 12 months post injury or until return to normal function within 12 months, with measures of health service utilisation, impairment, disability, and health related quality of life. National estimates of the burden of injuries will be calculated by extrapolation from the sample population to national and regional computerised hospital in-patient, emergency department and mortality data. Discussion This study will provide more detailed data on the national burden of injuries than has previously been available in any country and will contribute to international collaborative efforts to more accurately assess the global burden of injuries. The results will be used to advise policy makers on prioritisation of preventive measures, support the evaluation of interventions, and provide guidance on the likely impact and degree of impairment and disability following specific injuries

Homocysteine levels in preterm infants: is there an association with intraventricular hemorrhage? A prospective cohort study.

BACKGROUND: The purpose of this study was to characterize total homocysteine (tHcy) levels at birth in preterm and term infants and identify associations with intraventricular hemorrhage (IVH) and other neonatal outcomes such as mortality, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and thrombocytopenia. METHODS: 123 infants \u3c 32 weeks gestation admitted to our Level III nursery were enrolled. A group of 25 term infants were enrolled for comparison. Two blood spots collected on filter paper with admission blood drawing were analyzed by a high performance liquid chromatography (HPLC) method. Statistical analysis included ANOVA, Spearman\u27s Rank Order Correlation and Mann-Whitney U test. RESULTS: The median tHcy was 2.75 micromol/L with an interquartile range of 1.34 - 4.96 micromol/L. There was no difference between preterm and term tHcy (median 2.76, IQR 1.25 - 4.8 micromol/L vs median 2.54, IQR 1.55 - 7.85 micromol/L, p = 0.07). There was no statistically significant difference in tHcy in 31 preterm infants with IVH compared to infants without IVH (median 1.96, IQR 1.09 - 4.35 micromol/L vs median 2.96, IQR 1.51 - 4.84 micromol/L, p = 0.43). There was also no statistically significant difference in tHcy in 7 infants with periventricular leukomalacia (PVL) compared to infants without PVL (median 1.55, IQR 0.25 - 3.45 micromol/L vs median 2.85, IQR 1.34 - 4.82 micromol/L, p = 0.07). Male infants had lower tHcy compared to female; prenatal steroids were associated with a higher tHcy. CONCLUSION: In our population of preterm infants, there is no association between IVH and tHcy. Male gender, prenatal steroids and preeclampsia were associated with differences in tHcy levels

Monkeypox Disease Transmission in an Experimental Setting: Prairie Dog Animal Model

Monkeypox virus (MPXV) is considered the most significant human public health threat in the genus Orthopoxvirus since the eradication of variola virus (the causative agent of smallpox). MPXV is a zoonotic agent endemic to forested areas of Central and Western Africa. In 2003, MPXV caused an outbreak in the United States due to the importation of infected African rodents, and subsequent sequential infection of North American prairie dogs (Cynomys ludovicianus) and humans. In previous studies, the prairie dog MPXV model has successfully shown to be very useful for understanding MPXV since the model emulates key characteristics of human monkeypox disease. In humans, percutaneous exposure to animals has been documented but the primary method of human-to-human MPXV transmission is postulated to be by respiratory route. Only a few animal model studies of MPXV transmission have been reported. Herein, we show that MPXV infected prairie dogs are able to transmit the virus to naive animals through multiple transmission routes. All secondarily exposed animals were infected with MPXV during the course of the study. Notably, animals secondarily exposed appeared to manifest more severe disease; however, the disease course was very similar to those of experimentally challenged animals including inappetence leading to weight loss, development of lesions, production of orthopoxvirus antibodies and shedding of similar levels or in some instances higher levels of MPXV from the oral cavity. Disease was transmitted via exposure to contaminated bedding, co-housing, or respiratory secretions/nasal mucous (we could not definitively say that transmission occurred via respiratory route exclusively). Future use of the model will allow us to evaluate infection control measures, vaccines and antiviral strategies to decrease disease transmission

Phase I trial of intravesical Suramin in recurrent superficial transitional cell bladder carcinoma

Suramin is an antitrypanosomal agent with antineoplastic activity, but with serious systemic side effects. We administered Suramin intravesically to determine a concentration with low toxicity but with evidence of a pharmacodynamic effect, to recommend a dose level for phase II trials. This was an open-labelled, nonrandomised dose-escalation phase I study. In all, 12 patients with a history of recurrent superficial bladder cancer were grouped into four dose levels (10–150 mg ml−1 in 60 ml saline). Six catheter instillations at weekly intervals were used. Cystoscopy and biopsy were performed before and 3 months after the start of treatment. Suramin was assayed using high-performance liquid chromatography, vascular endothelial growth factor (VEGF) using ELISA (enzyme-linked immunosorbent assay), and urinary protein profile using surface-enhanced laser desorption ionisation mass spectroscopy (SELDI). Minimal systemic absorption of Suramin was found at the highest dose of 150 mg ml−1. Urinary VEGF was affected by Suramin at doses above 50 mg ml−1, corresponding to the estimated threshold of saturation of Suramin binding to urine albumin. SELDI showed a specific disappearance of urinary protein peaks during treatment. Intravesical Suramin shows lack of toxicity and low systemic absorption. The results of this phase I trial support expanded clinical trials of efficacy at a dose of 100 mg ml−1 intravesically

Current and Emerging Treatment Options for Castration-Resistant Prostate Cancer: A Focus on Immunotherapy

BACKGROUND: Castration-resistant prostate cancer is a disease with limited treatment options. However, the ongoing elucidation of the mechanisms underlying this disease continues to support the development of not only novel agents, but also innovative approaches. Among these therapies, immunotherapy has emerged as a promising strategy. DESIGN: This review article summarizes the most recent data from investigations of immunotherapies in castration-resistant prostate cancer (literature and congress searches current as of August 2011). RESULTS: Immunotherapeutic strategies such as passive immunization, vaccines, and particularly checkpoint blockade have demonstrated some efficacy as single agents. Elucidation of effective combinations of agents and drug regimens is ongoing but will require continued careful investigation, including the standardization of surrogate endpoints in clinical trials. CONCLUSIONS: It is hypothesized that the combination of immunotherapeutic agents with traditional and novel chemotherapeutics will potentiate the efficacy of the chemotherapeutics while maintaining manageable toxicity

Listeria monocytogenes in Milk Products

peer-reviewedMilk and milk products are frequently identified as vectors for transmission of Listeria monocytogenes. Milk can be contaminated at farm level either by indirect external contamination from the farm environment or less frequently by direct contamination of the milk from infection in the animal. Pasteurisation of milk will kill L. monocytogenes, but post-pasteurisation contamination, consumption of unpasteurised milk and manufacture of unpasteurised milk products can lead to milk being the cause of outbreaks of listeriosis. Therefore, there is a concern that L. monocytogenes in milk could lead to a public health risk. To protect against this risk, there is a need for awareness surrounding the issues, hygienic practices to reduce the risk and adequate sampling and analysis to verify that the risk is controlled. This review will highlight the issues surrounding L. monocytogenes in milk and milk products, including possible control measures. It will therefore create awareness about L. monocytogenes, contributing to protection of public health

The oncolytic effect in vivo of reovirus on tumour cells that have survived reovirus cell killing in vitro

The use of oncolytic viruses has received considerable attention in recent years and many viruses have proved to be effective against a variety of cancer models and a few are currently being used in clinical trials. However, the possible emergence and outcome of virus-resistant tumour cells has not been addressed. We previously reported the effective use of reovirus against lymphoid malignancies, including the Burkitt's lymphoma cell line Raji. Here we isolated in vitro persistently infected (PI) Raji cells, and cells ‘cured' of persistent reovirus infection (‘cured' cells). Both PI and cured Raji cells resisted reovirus infection and cell killing in vitro. In vivo, the PI cells were non-tumorigenic in SCID mice, but cured cells regained the parental cells' ability to form tumours. Tumour xenografts from the cured cells, however, were highly susceptible to reovirus oncolysis in vivo. This susceptibility was due to the proteolytic environment within tumours that facilitates reovirus infection and cell killing. Our results show that persistent infection by reovirus impedes tumour development and that although PI cells cleared of reovirus are tumorigenic, they are killed upon rechallenge with reovirus. Both the PI and cured states are therefore not likely to be significant barriers to reovirus oncolytic therapy

Can a single model explain both breast cancer and prostate cancer?

<p>Abstract</p> <p>Background</p> <p>The Estradiol-Dihydrotestosterone model of prostate cancer (PC) showed how the interaction of hormones with specific hormone receptors affected apoptosis. The same hormone can produce different effects, depending on which hormone receptor it interacts with.</p> <p>Model</p> <p>This model proposes that the first step in the development of most PC and breast cancer (BC) occurs when aromatase converts testosterone to estradiol (E2). A sufficiently high enough local level of E2 results in telomerase activity. The telomerase activity allows cell division and may lead to BC or PC, which will proliferate if the rate of cell division is greater than the rate of cell death. The effect of hormones on their hormone receptors will affect the rate of cell death and determine whether or not the cancer proliferates.</p> <p>Conclusion</p> <p>By minimizing bcl-2 and maximizing apoptotic proteins, new systemic treatments for BC and PC can be developed that may be more effective than existing treatments.</p

Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages

Macrophages play an essential role in the early immune response against Toxoplasma and are the cell type preferentially infected by the parasite in vivo. Interferon gamma (IFNγ) elicits a variety of anti-Toxoplasma activities in macrophages. Using a genome-wide CRISPR screen we identify 353 Toxoplasma genes that determine parasite fitness in naїve or IFNγ-activated murine macrophages, seven of which are further confirmed. We show that one of these genes encodes dense granule protein GRA45, which has a chaperone-like domain, is critical for correct localization of GRAs into the PVM and secretion of GRA effectors into the host cytoplasm. Parasites lacking GRA45 are more susceptible to IFNγ-mediated growth inhibition and have reduced virulence in mice. Together, we identify and characterize an important chaperone-like GRA in Toxoplasma and provide a resource for the community to further explore the function of Toxoplasma genes that determine fitness in IFNγ-activated macrophages