Optical effects of exposing intact human lenses to ultraviolet radiation and visible light

<p>Abstract</p> <p>Background</p> <p>The human lens is continuously exposed to high levels of light. Ultraviolet radiation is believed to play a causative role in the development of cataract. In vivo, however, the lens is mainly exposed to visible light and the ageing lens absorbs a great part of the short wavelength region of incoming visible light. The aim of the present study was to examine the optical effects on human lenses of short wavelength visible light and ultraviolet radiation.</p> <p>Methods</p> <p>Naturally aged human donor lenses were irradiated with UVA (355 nm), violet (400 and 405 nm) and green (532 nm) lasers. The effect of irradiation was evaluated qualitatively by photography and quantitatively by measuring the direct transmission before and after irradiation. Furthermore, the effect of pulsed and continuous laser systems was compared as was the effect of short, intermediate and prolonged exposures.</p> <p>Results</p> <p>Irradiation with high intensity lasers caused scattering lesions in the human lenses. These effects were more likely to be seen when using pulsed lasers because of the high pulse intensity. Prolonged irradiation with UVA led to photodarkening whereas no detrimental effects were observed after irradiation with visible light.</p> <p>Conclusions</p> <p>Irradiation with visible light does not seem to be harmful to the human lens except if the lens is exposed to laser irradiances that are high enough to warrant thermal protein denaturation that is more readily seen using pulsed laser systems.</p

Group differences in physician responses to handheld presentation of clinical evidence: a verbal protocol analysis

<p>Abstract</p> <p>Background</p> <p>To identify individual differences in physicians' needs for the presentation of evidence resources and preferences for mobile devices.</p> <p>Methods</p> <p>Within-groups analysis of responses to semi-structured interviews. Interviews consisted of using prototypes in response to task-based scenarios. The prototypes were implemented on two different form factors: a tablet style PC and a pocketPC. Participants were from three user groups: general internists, family physicians and medicine residents, and from two different settings: urban and semi-urban. Verbal protocol analysis, which consists of coding utterances, was conducted on the transcripts of the testing sessions. Statistical relationships were investigated between staff physicians' and residents' background variables, self-reported experiences with the interfaces, and verbal code frequencies.</p> <p>Results</p> <p>47 physicians were recruited from general internal medicine, family practice clinics and a residency training program. The mean age of participants was 42.6 years. Physician specialty had a greater effect on device and information-presentation preferences than gender, age, setting or previous technical experience. Family physicians preferred the screen size of the tablet computer and were less concerned about its portability. Residents liked the screen size of the tablet, but preferred the portability of the pocketPC. Internists liked the portability of the pocketPC, but saw less advantage to the large screen of the tablet computer (F[2,44] = 4.94, p = .012).</p> <p>Conclusion</p> <p>Different types of physicians have different needs and preferences for evidence-based resources and handheld devices. This study shows how user testing can be incorporated into the process of design to inform group-based customization.</p

Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis

Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R(2) = 0.273; Spearman rho = 0.581; P < 0.001) and CRP (R(2) = 0.132; Spearman rho = 0.455, P < 0.001). Temporal profiling showed early tryptophan depletion and contemporaneous 3-hydroxykynurenine elevation. Furthermore, plasma concentrations of 3-hydroxykynurenine paralleled systemic inflammation and AP severity. These findings support the rationale for investigating early intervention with a KMO inhibitor, with the aim of reducing the incidence and severity of AP-associated organ dysfunction

Greater accordance with the Dietary Approaches to Stop Hypertension dietary pattern is associated with lower diet-related greenhouse gas production but higher dietary costs in the United Kingdom.

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet is a proven way to prevent and control hypertension and other chronic disease. Because the DASH diet emphasizes plant-based foods, including vegetables and grains, adhering to this diet might also bring about environmental benefits, including lower associated production of greenhouse gases (GHGs). OBJECTIVE: The objective was to examine the interrelation between dietary accordance with the DASH diet and associated GHGs. A secondary aim was to examine the retail cost of diets by level of DASH accordance. DESIGN: In this cross-sectional study of adults aged 39-79 y from the European Prospective Investigation into Cancer and Nutrition-Norfolk, United Kingdom cohort (n = 24,293), dietary intakes estimated from food-frequency questionnaires were analyzed for their accordance with the 8 DASH food and nutrient-based targets. Associations between DASH accordance, GHGs, and dietary costs were evaluated in regression analyses. Dietary GHGs were estimated with United Kingdom-specific data on carbon dioxide equivalents associated with commodities and foods. Dietary costs were estimated by using national food prices from a United Kingdom-based supermarket comparison website. RESULTS: Greater accordance with the DASH dietary targets was associated with lower GHGs. Diets in the highest quintile of accordance had a GHG impact of 5.60 compared with 6.71 kg carbon dioxide equivalents/d for least-accordant diets (P < 0.0001). Among the DASH food groups, GHGs were most strongly and positively associated with meat consumption and negatively with whole-grain consumption. In addition, higher accordance with the DASH diet was associated with higher dietary costs, with the mean cost of diets in the top quintile of DASH scores 18% higher than that of diets in the lowest quintile (P < 0.0001). CONCLUSIONS: Promoting wider uptake of the DASH diet in the United Kingdom may improve population health and reduce diet-related GHGs. However, to make the DASH diet more accessible, food affordability, particularly for lower income groups, will have to be addressed.Supported by the British Heart Foundation (BHF), Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust under the auspices of the UK Clinical Research Collaboration. PS was supported by the BHF grant number 021/P&C/Core/2010/HPRG. AM was supported by the Oxford Martin School.This is the final published version. It first appeared at http://dx.doi.org/10.3945/ajcn.114.09063

Preventive Pharmacotherapy for Cardiovascular Disease: A Modelling Study Considering Health Gain, Costs, and Cost-Effectiveness when Stratifying by Absolute Risk

Cardiovascular disease (CVD) is the leading cause of death internationally. We aimed to model the impact of CVD preventive double therapy (a statin and anti-hypertensive) by clinician-assessed absolute risk level. An established and validated multi-state life-table model for the national New Zealand (NZ) population was adapted. The new version of the model specifically considered the 60-64-year-old male population which was stratified by risk using a published NZ-specific CVD risk equation. The intervention period of treatment was for five years, but a lifetime horizon was used for measuring benefits and costs (a five-year horizon was also implemented). We found that for this group offering double therapy was highly cost-effective in all absolute risk categories (eg, NZ$1580 per QALY gained in the >20$3990). Even in the lowest risk stratum (≤5% risk in 5 years), the cost per QALY was only NZ$25,500 (NZ$28,200 and US$19,100 in 2018). At an individual level, the gain for those who responded to the screening offer and commenced preventive treatment ranged from 0.6 to 4.9 months of quality-adjusted life gained (or less than a month gain with a five-year horizon). Nevertheless, at the individual level, patient considerations are critical as some people may decide that this amount of average health gain does not justify taking daily medication

Tryptophan-derived UV-filter compounds covalently bound to lens proteins are photosensitizers of oxidative damage

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Human lens chemistry - UV filters and cataract

The primate lens contains fluorescent tryptophan derived compounds known as UV filters. These absorb UV light and protect the lens from UV induced photo-damage. The major UV filters are 3-hydroxykynurenine O-Beta-D-glucoside, 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O-Beta-D-glucoside, kynurenine and 3-hydroxykynurenine. As the lens ages, a broad spectrum of molecular and biochemical changes occurs. We have shown that the UV filter compounds at physiological pH undergo spontaneous deamination, and bind to lens proteins and lens nucleophiles.(1,2) We have also demonstrated that kynurenine bound to lens proteins become highly susceptible to photo-oxidation in the presence of UV light and generates protein damage.(3) A greater understanding of the UV protective and photosensitising mechanisms of known human lens UV filters, and determination of as yet unidentified UV filters, is therefore required. The identification, synthesis and properties of human lens UV filters will be discussed. 1) Vazquez S., et al., J. Biol. Chem., 277, 4867-4873 (2002) 2) Hood B.D., et al., J. Biol. Chem., 274, 32547-32550 (1999) 3) Parker N.R., et al., Free Radical Biol. & Med., 37, 1479-1489 (2004)1 page(s

Tryptophan-derived ultraviolet filter compounds covalently bound to lens proteins are photo sensitizers of oxidative damage

The human eye is chronically exposed to light of wavelengths > 300 nm. In the young human lens, light of wavelength 300-400 nm is predominantly absorbed by the free Trp derivatives kynurenine (Kyn), 3-hydroxykynurenine (3OHKyn), and 3-hydroxykynurenine-O-β-D-glucoside (3OHKynG). These ultraviolet (UV) filter compounds are poor photosensitizers. With age, the levels of the free UV filters in the lens decreases and those of protein-bound UV filters increases. The photochemical behavior of these protein-bound UV filters and their role in UV damage are poorly elucidated and are examined here. UVA illumination of protein-bound UV filters generated peroxides (principally H2O2) in a metabolite-, photolysis-time-, and wavelength-dependent manner. Unmodified proteins, free Trp metabolites, and Trp metabolites that do not bind to lens proteins gave low peroxide yields. Protein-bound 3OHKyn (principally at Cys residues) yielded more peroxide than comparable Kyn and 3OHKynG adducts. Studies using D2O and sodium azide implicated 1O2 as a key intermediate. Illumination of the protein-bound adducts also yielded protein-bound Tyr oxidation products (DOPA, di-tyrosine) and protein cross-links via alternative mechanisms. These data indicate that the covalent modification of lens proteins by Kyn derivatives yields photosensitizers that may enhance oxidation in older lenses and contribute to age-related nuclear cataract.12 page(s