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This report aimed to characterize clinical and imaging characteristics and outcomes of the patients with lower cervical spine injury combined with spinal cord paralysis who underwent posterior cervical spine surgery.Between January 2019 and December 2020, a retrospective evaluation of prospectively collected data at one institution was conducted. We included all patients who were diagnosed with subaxial cervical spine injuries (C3-7), had spinal cord paralysis, and underwent posterior cervical spine surgery. Clinical profile, preoperative characteristics, intraoperative data, and postoperative outcomes were retrieved from prospective patients' medical records and computerized database.Among 70 selected patients, most were male (66, 94.29%) and the average age was 48.41 ± 14.33 years. Most of them worked in agriculture (90.4%). Clinical symptoms included neck pain (58, 82.86%), cervical radiculopathy (50, 71.43%), loss of sensation (44, 62.86%), and decreased sensation (21, 30.00%). The most frequent cervical spinal injuries involved C5 (28.57%), followed by C7 (14.29%). Circular muscle dysfunction was present in 65 (92.86%) patients. Early complications included respiratory failure (12.85%), pneumonia (11.42%), bedsores (8.57%), and urinary tract infection (7.14%). Common late complications included movement disorder (48.21%), muscle weakness and stiffness (37.50%), sensory disturbances (32.14%), urinary tract infection (17.86%), bedsores (16.07%), and pneumonia (5.36%). Patients after surgery and at follow-up had a significant improvement compared to preoperative assessment according to the AIS classification, and recovery of smooth muscle. Three patients died within 1 month following surgery, 3 within 1-3 month(s), 2 within 3-6 months, and 1 case beyond 6 months.In hospital-based clinical condition with limited practice approach, our study indicated specific clinical and imaging characteristics of Vietnamese patients with lower cervical spine injury combined with spinal cord paralysis. With high postoperative mortality rate, commonly late complications after posterior cervical spine surgical approach were pain and difficulty in neck movement, muscle weakness and stiffness, and nerve root pain.

Color rendering index (CRI) and luminous efficacy (LE) are two key performance factors of white LEDs (WLED). While most recent works in optics focus on methodology to improve these factors, little attention has been dedicated to chemical composition of materials. This paper studies the effect of Sr2.41F2.59B20.03O74.8:Eu0.12,Sm0.048 phosphor (SrSm), in terms of concentration and particle size on CRI and LE of 8500 K - WLEDs. Importantly, the molar mass of the componential ions in SrSm are calculated to shed light on the connection between the chemical composition of the material of interest and the performance of WLEDs. Results show that CRI can be improved to a value of around 86 by boosting red-light components in WLEDs, for all 3 major configurations: conformal, in-cup, and remote phosphor. CRI value tends to decrease with larger size of particles, while LE value goes in the reverse direction. On the other hand, both CRI and LE appear to be reduced at higher concentration of SrSm. This light attenuation is analyzed by using the Lambert-Beer law and Mie-scattering theory.

At the present time, color homogeneity and luminous flux are the two essentials utilized to appraise high-quality phosphor-converted LEDs (pcLEDs). In this paper, we present the search for the optimal selection among scattering enhancement particles (SEPs) to apply to improve these essentials for pcLEDs having correlated color temperature of 8500 K. The interested contenders include CaCO3, CaF2, SiO2, and TiO2. Each of them is added to yellow phosphor compounding (Y3Al5O12:Ce3+). Firstly, the LightTools program is employed to do the optical simulations. Secondly, the obtained results are verified and analyzed based on Mie scattering theory. The scattering computation of SEPs includes the scattering coefficients, the anisotropic scattering, the reduced scattering and the scattering amplitudes at 455 and 595 nm. It is observed that TiO2 particles provide the highest color homogeneity among the SEPs but the luminous flux reduces significantly as its concentration increases. By using CaCO3 particles, ...

Laser thermochemical recording is a flexible method for direct writing the binary planar structures (for instance, diffractive optical elements) by a local laser-induced oxidation of thin metal films. Unfortunately, due to excess of influencing parameters, search for regimes of high-resoluted recording could be complicated. The presented article proposes the way to analyze the hard-to-reach regimes of laser recording by modeling them with more convenient regimes (with different geometric and/or thermochemical parameters) based on their physical similarity.

Gamma-aminobutyric acid (GABA) is a non-protein amino acid widespread in Nature. Among the various uses of GABA, its lactam form 2-pyrrolidone can be chemically converted to the biodegradable plastic polyamide-4. In metabolism, GABA can be synthesized either by decarboxylation of l-glutamate or by a pathway that starts with the transamination of putrescine. Fermentative production of GABA from glucose by recombinant Corynebacterium glutamicum has been described via both routes. Putrescine-based GABA production was characterized by accumulation of by-products such as N-acetyl-putrescine. Their formation was abolished by deletion of the spermi(di)ne N-acetyl-transferase gene snaA. To improve provision of l-glutamate as precursor 2-oxoglutarate dehydrogenase activity was reduced by changing the translational start codon of the chromosomal gene for 2-oxoglutarate dehydrogenase subunit E1o to the less preferred TTG and by maintaining the inhibitory protein OdhI in its inhibitory form by changing amino acid residue 15 from threonine to alanine. Putrescine-based GABA production by the strains described here led to GABA titers up to 63.2 g L-1 in fed-batch cultivation at maximum volumetric productivities up to 1.34 g L-1 h-1 , the highest volumetric productivity for fermentative GABA production reported to date. Moreover, GABA production from the carbon sources xylose, glucosamine, and N-acetyl-glucosamine that do not have competing uses in the food or feed industries was established. Biotechnol. Bioeng. 2017;114: 862-873. © 2016 Wiley Periodicals, Inc.

The purpose of this article is to describe four main areas of falls-prevention intervention for older adults who are blind or visually impaired. When integrated into multifactorial programs, interventions pertaining to education, medical assessment, exercise and physical activity, and environmental assessment and modification have been shown to be effective in falls reduction. These areas of intervention are discussed with respect to specific concerns of older adults who are blind or visually impaired. In describing these areas of intervention, the increasing need for cross-disciplinary falls-prevention programs designed specifically for older persons with vision loss, as well as research demonstrating the efficacy of multidisciplinary programs designed for this group, are emphasized.

In this study, contact lenses were prepared through the polymerization of tris-(trimethyl-silyl-propyl-methacrylate) (TRIS), N,N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP), and cross-linked with ethylene glycol dimethylacrylate (EGDMA). The equilibrium water content (EWC), oxygen permeability (Dk), light transmittance, and in vitro cytotoxicity of TRIS-DMA-NVP with various ratios were measured. The results showed that the EWC increased while the Dk decreased with the increase of NVP content. For the sample with 25 wt% NVP, the EWC attained 53% whereas the Dk decreased to 46 barrers. All these lenses exhibited light transmittance over than 95%. In addition, all these lenses exhibited no inhibition to the growth of L292 fibroblasts. Thus, this study showed that TRIS-DMA-NVP can be applicable for making contact lens., {"references":["S. L. Willis, J. L. Court, R. P. Redman, J.-H. Wang, S. W. 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Yang, \"Improvement of the surface wettability of silicone hydrogel contact lenses via layer-by-layer self-assembly technique,\" Colloids Surf., B, vol. 136, pp. 735-743, 2015.\n[13]\tD. T. R. Austin and B. P. Hills, \"Two-dimensional NMR relaxation study of the pore structure in silicone hydrogel contact lenses,\" Appl. Magn. Reson., vol. 35, pp. 581-591, 2009.\n[14]\tJ. J. Nichols, G. L. Mitchell, and G. W. Good, \"The reliability and validity of hand-held refractometry water content measures of hydrogel lenses,\" Optom. Vis. Sci., vol. 80, pp. 447-453, 2003.\n[15]\tI. Tranoudis and N. Efron, \"Water properties of soft contact lens materials,\" Contact Len Anterio, vol. 27, pp. 193-208, 2004.\n[16]\tC. Maldonado-Codina and N. Efron, \"Hydrogel lenses-material and manufacture: a review,\" Optometry in Practice, vol. 4, pp. 101-115, 2003.\n[17]\tA. M. Parambil, Y. M. Puttaiahgowda, and P. Shankarappa, \"Copolymerization of N-Vinyl pyrrolidone with methyl methacrylate by Ti (III)-DMG redox initiator,\" Turk. J. Chem., vol. 36, pp. 397-409, 2012.\n[18]\tZ.-B. Zhao, S.-S. An, H.-J. Xie, X.-L. Han, F.-H. Wang, et al., \"The Relationship between the Hydrophilicity and Surface Chemical Composition Microphase Separation Structure of Multicomponent Silicone Hydrogels,\" J. Phys. Chem. B., vol. 119, pp. 9780-9786, 2015.\n[19]\tJ. Wang and X. Li, \"Preparation and characterization of interpenetrating polymer network silicone hydrogels with high oxygen permeability,\" J. Appl. Polym. Sci., vol. 116, pp. 2749-2757, 2010.\n[20]\tK. French, \"Contact lens material properties. Part 3–Oxygen performance,\" Optician, vol. 230, pp. 16-21, 2005.\n[21]\tJ. Pozuelo, V. Compañ, J. M. González-Méijome, M. González, and S. Mollá, \"Oxygen and ionic transport in hydrogel and silicone-hydrogel contact lens materials: an experimental and theoretical study,\" J. Membr. Sci., vol. 452, pp. 62-72, 2014.\n[22]\tJ.-j. Wang and X.-s. Li, \"Improved oxygen permeability and mechanical strength of silicone hydrogels with interpenetrating network structure,\" Chin. J. Polym. Sci., vol. 28, pp. 849-857, 2010\n[23]\tM. Korogiannaki, G. Guidi, L. Jones, and H. Sheardown, \"Timolol maleate release from hyaluronic acid-containing model silicone hydrogel contact lens materials,\" J. Biomater. Appl., vol. 30, pp. 361-376, 2015.\n[24]\tLuensmann, D. and L. Jones, Protein deposition on contact lenses: the past, the present, and the future. Contact Lens and Anterior Eye, 2012. 35(2): p. 53-64."]}

To evaluate the safety, tolerability, pharmacokinetics, and dose-limiting toxicities of a single intravitreal (IVT) injection of PF-04523655, a 19-nucleotide, O-methyl stabilized, double-stranded small interfering ribonucleic acid targeting the RTP801 gene in patients with neovascular age-related macular degeneration (AMD).Prospective, phase 1, clinical multicentre trial, enrolled 27 patients with neovascular AMD unresponsive to prior treatment and best corrected visual acuity (BCVA) ≤ 20/200 in the study eye in stratum 1: (dose-escalating, open-label: 50 to 3000 μg of PF-04523655) and 27 patients who had potential to benefit from therapy and BCVA of ≤ 20/100 and ≥ 20/800 in stratum 2 (parallel, masked study of 1000, 1500, 2250, and 3000 μg of PF-04523655). The primary outcome was safety and tolerability assessment as well as pharmacokinetic profiling following a single IVT injection of PF-04523655.Doses of PF-04523655 ≥ 400 μg were generally detectable in the plasma at 1, 4, and 24 h post-injection. And all doses were below the lowest level of quantification by day 14. A single IVT injection of 50 to 3000 μg of PF-045237655 was generally safe and well tolerated over 24 months. There were no dose-limiting toxicities.A single IVT injection of PF-0523655 ≤ 3000 μg seems safe and well tolerated in eyes with neovascular AMD.

Uveitis refers to a group of ocular inflammatory diseases that can lead to blindness. For years, researchers have been trying to decipher the underlying mechanisms and develop therapeutic strategies using the model of experimental autoimmune uveitis (EAU). Recently, αA-crystallin has been found to be upregulated in EAU and can even ameliorate its severity through different mechanisms, suggesting its use as a potent therapeutic factor against uveitis. Here we review the protective role of αA-crystallin and discuss its functional mechanisms in EAU.

The tumor suppressor, p53 regulates a large number of target genes to control cell proliferation and apoptosis. In addition, it is also implicated in the regulation of cell differentiation in muscle, the circulatory system and various carcinoma tissues. We have recently shown that p53 also controls lens differentiation. Regarding the mechanism, we reveal that p53 directly regulates several genes including c-Maf and Prox1, two important transcription factors for lens differentiation, and αA and βA3/A1, the lens differentiation markers. In the present study, we present evidence to show that the γA-crystallin gene distal promoter and the first intron also contain p53 binding sites and are capable of mediating p53 control during mouse lens development. First, gel mobility shifting assays revealed that the p53 protein in nuclear extracts from human lens epithelial cells (HLE) directly binds to the p53 binding sites present in the γA-crystallin gene. Second, the exogenous wild type p53 induces the dose-dependent expression of the luciferase reporter gene driven by the basic promoter containing the γA-crystallin gene p53 binding site. In contrast, the exogenous dominant negative mutant p53 causes a dose-dependent inhibition of the same promoter. Third, ChIP assays revealed that p53 binds to the γA-crystallin gene promoter in vivo. Finally, in the p53 knockout mouse lenses, the expression level of the γAcrystallin gene was found attenuated in comparison with that in the wild type mouse lenses. Together, our results reveal that p53 regulates γA-crystallin gene expression during mouse lens development. Thus, p53 directly regulates all 3 types of crystallin genes to control lens differentiation.

This paper reports on the development of an on-line flow rheometer for characterising the rheological behaviour of settling mineral slurries. The instrument is a modified concentric cylinder viscometer in which the slurry is continuously circulated to keep the particles in suspension. The rheometer is designed based on the fundamentals of helical flow, which is the combination of tangential Couette and axial annular flows, and thus satisfies both the basic requirements of viscometric principles and the restrictions caused by the heterogeneous nature of the material. A strong emphasis is placed on developing a correct and accurate method for extracting fundamental rheological properties from the experimental data, without relying on any empirical calibrations or corrections. The data reduction procedure developed is firmly based on the theory of helical flow and has been extensively tested and validated with model fluids of different rheological behaviour. Testing of the flow rheometer and the dat...

Aim There is evidence that interaction between angiotensin II type 1 receptor A1166C gene polymorphism and angio-tensin I-converting enzyme Insertion/Deletion gene variation might have an effect on the risk of myocardial infarction. The study was carried out in a population of 2244 male Caucasians, whose coronary anatomy was defined by means of coronary angiography. We analysed the relationship, on the risk of ischaemic heart disease, of angiotensin II type 1 receptor A1166C gene variation, not only to myocardial infarction but also to coronary artery disease, and its potential interaction with angio-tensin I-converting enzyme Insertion/Deletion gene polymorphism. Methods and Results No association was detected between angiotensin II type 1 receptor A1166C gene polymorphism and coronary artery disease. Similarly, there was no link to myocardial infarction, either in the total population or in low risk groups. In addition, most importantly, we found no interaction between angiotensin II type 1 receptor A1166C gene variation and angiotensin I-converting Insertion/Deletion polymorphism, either in connection with the risk of coronary artery disease or myocardial infarction. Conclusion This angiotensin II type 1 receptor A1166C gene variation is not associated with any detectable increase in risk of ischaemic heart disease. The findings of the present study do not suggest that, as regards risk of coronary artery disease and myocardial infarction, there is interaction between gene polymorphism and angiotensin I-converting enzyme Insertion/Deletion gene variation. The European Society of Cardiology

Unoperated cataract is the leading cause of blindness in the developing world. Many developing countries now use extracapsular cataract extraction (ECCE) with intra-ocular lens insertion (IOL) in their cataract blindness-prevention programmes. To date, little research has been directed at visual outcomes and complication rates of ECCE/IOL surgery in developing countries.We conducted a follow-up study of 155 eyes approximately 12 months after ECCE/IOL surgery by eight local eye surgeons in Central Vietnam. We report the findings for the 144 eyes (93%) successfully reviewed. All subjects underwent manual ECCE with insertion of a three-piece posterior chamber IOL. All eyes were also assessed for the presence and severity of posterior capsule opacification (PCO) using a newly developed grading system.Overall, 110 eyes (75%) had uncorrected visual acuitiesor = 6/24 and 107 eyes (74%) had best spherically corrected visual acuitiesor = 6/18. Some degree of PCO was found in 40% of eyes, but was graded as visually significant in only 4% of eyes. No major sight-threatening complications were noted. A portable neodymium:yttrium aluminium garnet (Nd:YAG) laser was used to perform capsulotomies on all eyes with visually significant PCO. There were no laser complications noted.At approximately 1 year after ECCE/IOL, the visual outcomes for subjects in this cohort were favourable and complication rates were low. Posterior chamber opacification was not a major cause of vision impairment in this cohort. Portable Nd:YAG lasers may provide an effective solution to the problem of visually significant PCO occurring in developing countries as a late complication of extracapsular surgery. These findings support an increasing role for ECCE/PCIOL surgery by trained local eye surgeons in developing countries.

The study aims to identify the association between the baseline retinal vascular calibre and visual outcome of patients with diabetic macular oedema (DMO) treated with intravitreal ranibizumab.The 1-M field (as defined in the ETDRS study) of the digital colour fundus photographs of DMO patients who had been treated primarily with ranibizumab in a clinical trial was assessed. Of the 84 patients, 25 had gradable retinal photographs that could be subjected to analyses by the Interactive Vessel Analysis (IVAN) software at baseline. The average retinal vascular calibre of the six largest venules (CRVE) and the six largest arterioles (CRAE) in the peripapillary area (0.5 and 1 disc diameter from the optic disc margin) was measured. The relationship between CRVE and CRAE at baseline and the change in visual acuity at month 12 was assessed using the Mann-Whitney U test.Ten eyes from 10 patients who had shown an improvement of ≥2 lines of best corrected visual acuity (BCVA) at month 12 had a wider baseline CRVE (248.3±24.5 μm) compared with the 15 eyes from 15 patients who did not show the improvement of ≥2 lines (226.6±44.8 μm, P0.05). The baseline CRAE did not differ significantly in these patients (156.1±22.7 vs 142±17.5 μm, P=0.17).A wider baseline retinal venular calibre may be a predictor of better visual outcome in DMO eyes treated with ranibizumab. Further prospective studies with a larger sample size and a broader range of disease severity and visual acuity are needed to confirm this finding.

Patients with diabetic retinopathy (DR) may experience a reduction in retinal oxygen saturation (SO2). Close monitoring with a fundus ophthalmoscope can help in the prediction of the progression of disease. In this paper we present a noninvasive instrument based on structured illumination aimed at measuring the retina optical properties including oxygen saturation. The instrument uses two wavelngths one in the NIR and one visible, a fast acquisition camera, and a splitter system that allows for contemporaneous collection of images at two different wavelengths. This scheme greatly reduces eye movement artifacts. Structured illumination was achieved in two different ways, firstly several binary illumination masks fabricated using laser micro-machining were used, a near-sinusoidal projection pattern is ultimately achieved at the image plane by appropriate positioning of the binary masks. Secondarily a sinusoidal pattern printed on a thin plastic sheet was positioned at image plane of a fundus ophthalmoscope. The system was calibrated using optical phantoms of known optical properties as well as an eye phantom that included a 150μm capillary vessel containing different concentrations of oxygenated and deoxygenated hemoglobin.

This article discusses the role of home assessment and environmental modification in reducing the risk of falls and helping older adults and persons with disabilities live in the community. This article reviews the research on the efficacy of home environmental assessment and modification. Researchers agree that integrated risk-management programs that emphasize on multiple interventions, including professional home-hazard assessment, along with home modifications are most effective for improving function and reducing falls. Important steps for implementing home modifications for persons at risk of falling are discussed, including exploring fall-risk factors and the effects of home modifications, identifying what changes are needed through home assessments, identifying sources of payment, and finding qualified installers and products.

We present the development of setup composed of a retinal oximeter and a blood velocimeter implemented on a regular fundus ophthalmoscope. The oximeter part can acquire nine wavelength-dependent sub-images of the patient fundus in a single snapshot. The fundus image is projected on a large format CCD by an array of nine lenses and wavelength selection is provided by a filter array. Higher wavelength images help establishing melanin absorption, which is further extrapolated to shorter wavelength and subtracted from the absorption images. The remaining shorter wavelength subimages are used measure the oxygen saturation in the retina by fitting oxy- and deoxy-hemoglobin absorption curves. The setup was calibrated with optical phantoms of know optical properties. The velocimeter part of the setup relies on following clusters of erythrocytes to assess the velocity of blood.

Objectives: To assess direct effects of self-rated vision, home modifications, and limb functioning, and moderating effects of self-rated vision on change in functioning of upper and lower limbs on fall risk in older adults. Method: Logistic regression was used to analyze 2004 and 2006 waves of the Health and Retirement Study. Results: Effects of self-rated vision and home modifications in predicting falls decreased after controlling functioning in upper and lower extremities. Declines/gains in functioning across short periods of time superseded self-rated vision in predicting falls. No evidence was found for a moderating effect of vision status on limb functioning. Discussion: Poor self-rated vision may not be a good indicator of fall risk in older adults. Thus, for older adults with visual impairments, preserving residual limb functioning through exercise and activity has the important potential to reduce fall risk in addition to improving muscle and bone strength as well as improving balance and gait.

Aim:The aim of the study was to assess the safety and bioactivity of a single intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye in subjects with diabetic macular oedema (DMO).Methods:Five subjects with DMO, foveal thickness ⩾250 μm measured by optical coherence tomography (OCT), and best-corrected visual acuity (BCVA) between 20/40 and 20/320, were enrolled. Each participant received a single intravitreal injection of 4.0 mg of VEGF Trap-Eye followed by a 6-week observation period. Outcome measures included safety and biological activity, including changes in BCVA and excess retinal thickness assessed by OCT.Results:Injections of VEGF Trap-Eye were well tolerated with no ocular toxicity. One patient had an unrelated serious adverse event: hospitalisation for cellulitis of the left foot 27 days after injection of VEGF Trap-Eye. Median baseline BCVA was 36 ETDRS letters read at 4 m (not ETDRS visual acuity score; Snellen equivalent: 20/50) and median baseline excess central 1 mm foveal thickness (FTH) was 108 μm. At 4 weeks after injection, the median excess FTH was 59 μm and the median improvement in BCVA was nine letters. At 6 weeks after injection, four of the five patients showed improvement in excess FTH (median 74 μm; 31% reduction from baseline, p = 0.0625) and four of the five showed improvement in BCVA (median improvement of three letters).Conclusions:A single intravitreal injection of 4.0 mg of VEGF Trap-Eye was well tolerated and preliminary evidence of bioactivity was detected. These findings support additional studies investigating multiple injections of VEGF Trap-Eye in patients with DMO.

In completion of oil and gas wells, zonal isolation requires proper cement placement with adequate bonding to the casing and formation. To achieve a successful cementing operation, the cement slurry should be properly designed to enable effective displacement of the drilling fluid from the annulus between the casing and wellbore. This is a complex process, involving displacement of viscoplastic fluids in eccentric annuli. The rheology, flow rate, and interfacial mixing of these fluids have direct impact on the displacement efficiency. Reliable computational modeling of the dynamics of the displacement process is beneficial to properly perform pre‐job design and post‐job analysis of the cementing operation. Furthermore, experimental data are also used to validate numerical predictions. This paper presents a flow visualization study using a helical flow device with adjustable annular eccentricity and rotation of the inner cylinder. Displacement experiments were conducted with a variety of non‐Newtonian fluids to simulate the cement slurry—drilling mud displacement process.

Straight vegetable oils provide cleaner burning and renewable alternatives to diesel fuels, but their inherently high viscosities compared to diesel are undesirable for diesel engines. Lowering the viscosity can be achieved by either increasing the temperature of the oil or by blending it with diesel fuel, or both. In this work the viscosity of diesel fuel and vegetable oil mixtures at differing compositions is measured as a function of temperature to determine a viscosity‐temperature‐composition relationship for use in design and optimization of heating and fuel injection systems. The oils used are olive, soybean, canola and peanut oils which are commercially available. All samples tested between 20°C and 80°C exhibit time‐independent Newtonian behaviour. A modified Arrhenius relationship has been developed to predict the viscosity of the mixtures as functions of temperature and composition.

Bevacizumab (Avastin, Genentech) is a recombinant humanised, full length, anti-VEGF monoclonal antibody that binds all isoforms of VEGF-A. It has been shown to prolong survival of patients with advanced colon cancer when combined with 5-fluorouracil.1 In this report, we describe the effect of bevacizumab in two patients with choroidal neovascularisation (CNV) secondary to pathological myopia, which was refractory to other treatment. ### Patient 1 AM is a 36 year old white man who was diagnosed with subfoveal CNV caused by pathological myopia (right eye = −11.50 D, left eye = −11.50 D) in his left eye in September 2002 for which he received three photodynamic therapy (PDT) treatments. He developed subfoveal CNV in his right eye in June 2003 and received one PDT treatment combined with an intravitreous injection of 4 mg of triamcinolone acetonide. In May 2004, he presented with recurrent subfoveal CNV in his right eye and refused PDT. Off-label use of bevacizumab was discussed and after informed consent, the patient decided to proceed. Just before treatment in July 2004, best corrected visual acuity (VA) was 20/40 in the right eye and 20/25 in the left eye. There was a ring of hyperpigmentation centred on the fovea with a surrounding ring of subretinal blood and substantial subretinal fluid in the right eye (fig 1A). An optical coherence tomography (OCT) scan through the centre of the fovea confirmed the presence of extensive subretinal fluid (fig 1B, asterisks) with subretinal tissue in the centre of the fovea (arrowheads). An OCT map showed severe thickening and subretinal fluid throughout the centre of the macula (foveal thickness 510 μm, macular volume 9.29 mm3). In the left eye, there were pigmentary changes and no subretinal blood or fluid (foveal thickness, 201 μm). In the right eye, the early phase of a fluorescein angiography (FA) …

Age-Related Macular Degeneration (AMD) is, together with Diabetic Retinopathy, the most common cause of vision loss among adults in the U.S. and other developed countries. In the U.S., at least 1.7 million people have impaired vision due to AMD. Every year, more than 165,000 people contract AMD and 16,000 go blind from it, predominantly from a rapidly progressing form of the disease called "wet" AMD. Wet AMD is characterized by serious or hemorrhagic detachment of the retinal pigment epithelium and choroidal neovascularization. The macula has the highest concentration of photoreceptors facilitating central vision and permitting high-resolution visual acuity. The damage caused by the leakage and fibrovascular scarring in wet AMD leads to profound loss of central vision and severe loss of visual acuity (usually 20/200 or worse). People with wet AMD have several limitations, including inability to read, inability to recognize faces or drive, and the disease often leads to blindness. The onset of severe visual changes in wet AMD can occur suddenly. More than 400,000 Americans are currently affected by this form of the disease, and the incidence is rising rapidly with the aging of the population. Therefore, the serious consequences of this disease along with the limited treatment options and their effectiveness make this a very good candidate for a gene transfer treatment approach. The investigational agent, Ad(GV)PEDF.11D, is an E1-, partial E3-, E4- deleted replication-deficient, adenovirus serotype 5, gene transfer vector. The transgene in this vector is the cDNA for human pigment epithelium-derived factor (PEDF). PEDF is one of the most potent known antiangiogenic proteins found in humans. While Ad(GV)PEDF.11D is able to transduce many somatic cell types, the natural barrier to other tissues created by the retina limits the ability of Ad(GV)PEDF.11D to affect tissues other than in the eye. Intravitreal administration of Ad(GV)PEDF.11D provides a convenient means of delivering PEDF to the relevant cells within the eye likely to result in a more prolonged duration of effect versus administration of the PEDF protein alone. In three murine disease models (the laser-induced choroidal neovascularization model, the VEGF transgenic model, and the retinopathy of prematurity model) significant inhibition of neovascularization (up to 85%) was demonstrated with doses of Ad(GV)PEDF vectors ranging from 1 x 10(8) to 1 x 10(9) pu. In toxicology studies performed in Cynomolgus monkeys, a dose-related inflammatory response was observed. A dose of 1 x 10(8) pu caused no adverse effects, while the inflammatory response observed at 1 x 10(9) pu was minimal and fully reversible. The observed inflammatory response at doses of 1 x 10(10) and 5 x 10(10) pu were increasingly severe. The proposed clinical trial is an open-label, dose-escalation, phase I study to investigate the safety, tolerability and potential activity of intravitreal injection of Ad(GV)PEDF.11D in patients with wet AMD. Ad(GV)PEDF.11D will be injected once via intravitreal injection into the eye with the most advanced AMD based on visual acuity. Subjects will be age 50 or over and have severe wet AMD in at least one eye defined by a best-corrected vision of 20/200 or worse. The primary objectives of this investigation are: (1) to assess the safety, tolerability and feasibility of intravitreal injection of Ad(GV)PEDF.11D in patients with severe, neovascular AMD, (2) to identify the maximum tolerated dose (MTD) of Ad(GV)PEDF.11D, and (3) to get some indication of potential activity of Ad(GV)PEDF.11D.

To investigate the effect of Fas and Fas ligand (FasL) deficiency on the development of herpes stromal keratitis and on the von Szily model of herpes retinitis in C57BL/6 mice, which are ordinarily resistant to development of both of these herpetic diseases.Anterior chamber inoculation of the right eye of each mouse with various titers of HSV-1 (KOS strain) was performed. Both eyes of each mouse were enucleated on postinoculation day 15 and processed for histopathologic examination. HSV-1 was inoculated into one cornea of other mice, and the severity of stromal keratitis was scored.Contralateral destructive chorioretinitis developed in susceptible Balb/cByj mice (19/23); ipsilateral chorioretinitis did not occur (0/23). Stromal keratitis developed in susceptible C.AL-20 mice (15/16). None of the C57BL/6 (0/10 for keratitis or 0/20 for retinitis) developed inflammation. Neither did B6.SMN.C3H.gld (FasL deficient; 0/12 or 0/28) or B6.MRL.lpr (Fas deficient; 0/11 or 0/34) mice (keratitis or contralateral chorioretinitis). Minimal scattering of inflammatory cells in the contralateral retina but not destructive chorioretinitis was observed in two C57BL/6, three B6.SMN.C3H.gld, and five B6.MRL.lpr mice. Few inflammatory cells were also found in the ipsilateral vitreous and vitreoretinal interface (but not destructive chorioretinitis) of all C57BL/6, two gld, and three lpr mice.Immune dysregulation secondary to deficiency in Fas or FasL system does not influence the resistance of the C57BL/6 mice to develop herpes simplex keratitis or destructive herpes simplex chorioretinitis.

It was shown previously that platelet-activating factor receptors (PAF-Rs) inhibit invasiveness of colonic and kidney epithelial cells induced by the src and Met oncogenes via a pertussis toxin-sensitive mechanism. Therefore, Madin-Darby canine kidney (MDCKts.src) cells were stably transfected with constitutively activated forms of Galphao, Galphai1, Galphai2, Galphai3 (AGalphao/i), two Gbetagamma sequestering proteins [C-terminal end of beta-adrenergic receptor kinase (ct-betaARK) and the Galphat subunit of retinal G-protein transducin], and Gbeta1-Ggamma2 subunits alone or in combination. Cellular invasion induced by src, Met, and leptin was abrogated by the AGalphao/i, ct-betaARK, and Galphat-positive clones, but was induced by coexpression of Gbeta1gamma2. In contrast, invasion stimulated by the trefoil factors (TFFs) pS2 and intestinal trefoil factor in MDCKts.src cells or human colonic epithelial cells PCmsrc and HCT8/S11 was insensitive to PAF, AGalphao, AGalphai1, and AGalphai2, but was abolished by AGalphai3 and the protease-activated receptor-1 (PAR-1) agonist thrombin receptor-activating peptide. Depletion of free Gbetagamma heterodimers by ct-betaARK resulted in a remarkable decrease of cellular adhesion and spreading on collagen matrix. Our data demonstrate the following: 1) PAF-Rs impair cellular invasion induced by src, Met, and leptin via the activation of Galphao and Galphai1 to -3; 2) invasion induced by TFFs is selectively inhibited by PAR-1 receptors and Galphai3 activation; and 3) Gbetagamma dimers are required as positive effectors of invasion pathways induced by oncogenes and epigenetic factors. Thus, redistribution of Galphao/Galphai and Gbeta/gamma heterotrimeric G-proteins by PAF-R and PAR-1 exert differential functions on positive and negative signaling pathways involved in cellular invasion and may serve as potential targets for anticancer therapy.

We report the clinical findings and analysis of the immunoglobulin (Ig) composition of the vitreous of a 10-year-old girl with juvenile rheumatoid arthritis-associated uveitis. The vitreous had a schlieren appearance at the time of pars plana lensectomy and vitrectomy. Analysis of the vitreous fluid revealed marked elevation of IgG, IgM, IgA, and albumin levels relative to vitreous fluids from control patients without uveitis. The immunoglobulin coefficients were also elevated for the IgG and IgM classes of immunoglobulins. Immunofixation electrophoresis of the vitreous fluid revealed 2 distinct bands of restricted electrophoretic mobility. These studies suggest that there may be local (intraocular) production of immunoglobulins as an immunologic response in ocular inflammatory diseases such as juvenile rheumatoid arthritis-associated uveitis and that this immunologic response may be monoclonal (possibly biclonal or oligoclonal) in nature.

The platelet membrane glycoprotein IIb/IIIa functions as a receptor for fibrinogen and von Willebrand factor during platelet aggregation. In a small case-control study, evidence has been presented that the PlA2 allele of the platelet glycoprotein GPIIIa PlA/A2 gene polymorphism might be an independent risk factor for acute myocardial infarction (MI).We explored the association of the PlA1A2 to the severity of coronary artery disease (CAD), as assessed angiographically in 2252 male individuals, and to myocardial infarction (MI). The severity of coronary heart disease (CHD) was also estimated by calculating a CHD score according to Gensini. The PlA genotype was determined by allele specific restriction digestion. Relation of the PlA2 allele to CAD: In the total population, the frequency of the PlA2 allele was not associated to the presence or to the extent of CAD. Also the CHD scores of PlA1/PlA2 genotypes were essentially the same. However, after exclusion of individuals with high BMI (or =26.9 kg/m2) and/or low apoAI (1.43 g/l) PlA2PlA2 carriers had clearly higher CHD scores than PlA1PlA1 genotypes: PlA1PlA2 heterozygotes had intermediate values (p0.05). After division of the study population into one group of individuals without any angiographic signs of CAD (CHD score = 0) and into another group of patients with severe CAD (CHD score (or = 120), a strong association of the PlA2 allele with severe CAD was also found in the same low risk groups: e.g. exclusion of persons with high BMI and low apoAI resulted in an Odds ratio of 5.37 (1.46-19.7) (p0.02). Relation of the PlA2 allele to MI: No association was found between PlA1/PlA2 genotypes and risk of MI neither in the total population nor in low risk subgroups.Whereas no difference in the distribution of allele and genotype frequencies between controls and survivors of MI could be detected, the PlA2 allele is associated with CHD in low risk patients.

An experimental study on the time-dependent rheology of highly concentrated and flocculated suspensions of bauxite residue (red mud) is presented. Both the thixotropic breakdown with shear and recovery at rest have been quantitatively examined using a vane-shear instrument and a capillary rheometer. It is demonstrated that both the yield stress and the apparent viscosity of the material can be drastically reduced, by orders of magnitude, by shear-induced agitation with a simple anchor impeller. The rate of thixotropic decay is a function of solids concentration, agitation time and speed. With prolonged agitation, the flow properties are brought to an equilibrium level characterized by a finite yield stress and a shear rate-dependent (shear-thinning) viscosity. In the absence of shear, the yield stress gradually increases with time but at a rate considerably slower than the rate of decay in the shear field. Even after an extended rest period of several months, only a fraction of the initial yield stress can be regained. The observed behaviour has been interpreted in terms of a time-dependent but non-reversible transformation of a network structure of flocculated particles initially developed in the red mud. Using a structural kinetic approach, models have been developed for correlating the experimental kinetic data. The paper concludes with a discussion on the practical consequences of the work.

Techniques for measuring the fundamental flow properties of as-mined Victorian brown coal suspensions are developed. Flow properties are presented for Morwell, Yallourn and Loy Yang coals as a function of concentration for fixed particle size distribution. Even at the relatively low solids concentration of 20 to 30 percent by weight, the suspensions exhibit complex non-Newtonian characteristics. Generally at high concentration, the suspensions are thixotropic with a shear rate dependent viscosity and exhibit a yield stress. The inherent thixotropy of the coals can be exploited and it is technically but perhaps not economically feasible to transport the as-mined coals in a pipeline. The power requirement to pump the coals in a pipeline is found to be 10 to 30 times that required to pump black coal in the Black Mesa pipeline in the U.S.A. The differences in the rheological properties of the three coals is related to the surface properties of the coal particle — expressed in terms of carboxylate and inorganic cation content, and to differences in the pore volume of the coals. The flow characteristics of one coal can be converted to that of another simply by varying either the carboxylate or ionic content of the suspension.

The methods normally employed for shear rate calculations from concentric cylinder viscometer data generally are not applicable for fluids with a yield stress. In cylindrical systems with large radius ratios, as usually is the case with suspensions, the yield stress induces two possible flow regimes in the annulus. Unless the yield value is exceeded everywhere in the gap only part of the fluid can be sheared while the remaining region behaves like a solid plug. A correct calculation of the shear rate must take into account the presence of a variable effective gap width determined by the extent of the sheared layer. For time-independent yield stress fluids, a two-step procedure, which does not require any specific flow model, is proposed for analysing the experimental torque-speed data. Under the partially sheared condition, the shear rate can be computed exactly, whereas for the fully sheared flow the Krieger and Elrod approximation is satisfactory. The method is assessed by examining both semi-ideal data generated with a Casson fluid with known properties, and experimental data with an industrial suspension. A more complicated problem associated with characterization of time-dependent yield stress fluids is also identified and discussed. An approximate procedure is used to illustrate the dependence of the shear rate on time of shear in constant-speed experiments.