Stratum corneum biomarkers after in vivo repeated exposure to sub-erythemal dosages of ultraviolet radiation in unprotected and sunscreen (SPF 50+) protected skin.

BACKGROUND: There is a need for non-invasive biomarkers to assess in vivo efficacy of protective measures aiming at reducing ultraviolet radiation (UVR) exposure. Stratum corneum (SC) biomarkers showed to be promising markers for internal UVR dose and immune response. PURPOSE: To establish a dose-response relationship for SC biomarkers and explore their suitability for in vivo assessment of the blocking effect of two sunscreens with a high sun protection factor (SPF) (50+). METHODS: Twelve volunteers were exposed to a broad-spectrum UVB (280-320 nm), five times a week, during one week. Unprotected back skin was irradiated with 0.24, 0.48, 0.72 and 1.44 standard erythema dose (SED) and sunscreen-protected skin with 3.6 SED. SC samples for determination of the relative amount of cis-urocanic acid (cUCA) and thirteen immunological makers including cytokines and matrix metalloproteinases (MMP) were collected after each irradiation. RESULTS: cUCA sharply increased after the first irradiation in a dose-dependent fashion. However, it levelled-off after subsequent exposures and reached a plateau for the highest UV-dose after the third irradiation. None of the immunological markers showed dose-dependency. However, MMP-9, IL-1ß and CCL27 increased gradually from baseline during repetitive exposures to the highest UV-dose. Assessed from cUCA, both sunscreens blocked >98% of the applied UV-dose. CONCLUSIONS: cUCA is a sensitive, non-invasive marker of the internal UVR dose enabling in vivo assessment of the blocking effect of high SPF sunscreens in the UVB-region. Immunological SC markers show low sensitivity in detecting immune response at sub-erythemal UVR dosages, suggesting they might be suitable only at higher and/or repetitive UVR exposure.

Accounting for ingrowth of radioactive progeny in dose assessments: generic weighting factors for dose coefficients.

In this paper, we describe a practical and convenient method to include the contribution of the ingrowth of radioactive progeny in dose assessments of the corresponding parent nuclides. This method modifies the dose coefficients (DCs) of parent nuclides by adding weighted DCs of the corresponding daughter nuclides to them. Based on the decay kinetics of serial nuclear transformations, the progeny weighting factors, with values between 0 and 1, are derived by analysis of the time-integrated activity of each nuclide in the (branched) decay chain headed by a parent nuclide. Using the electronic, nuclear-decay database of Publication 107 of the International Commission on Radiological Protection (ICRP 2008), DC weighting factors for annual dose assessments are calculated for all daughter radionuclides in the decay chains and are tabulated in this paper. Weighting factors based on integration periods other than one year, ranging from 1 h-70 years, are also provided (see the supplementary material). With a priori established weighting factors, dose assessments become significantly simplified by considering the decay kinetics of only the parent nuclides and by applying the modified DCs. This ensures that the ingrowth of progeny is taken into account realistically. In some cases, one requires a conservative estimate of the dose, for instance when dealing with issues of the clearance of materials under regulatory control. Therefore, we adapted the weighting-factor method to derive conservative DC weighting factors for dose evaluations. These values are calculated for various integration periods and compared with those from an existing method adopted by the Euratom Article 31 Group of Experts and by the International Atomic Energy Agency. Identical progeny weighting factors are obtained for long-lived parent radionuclides, whereas for short-lived parent radionuclides, the new method can yield significantly larger values. For example, the weighting factor of I-131 (daughter of parent Te-131) increases from 0.002 to 1.0 based on an integration period of 1 year. The progeny DC weighting factors, derived based on nuclear transformations in exit-only decay chains, may not always be suitable for use in radiological dose evaluations. For instance, when environmental removal pathways are dominant, the application of these weighting factors may have its limitations. This paper, therefore, provides guidance on the proper selection and application of weighting factors.

SUDOQU, a new dose-assessment methodology for radiological surface contamination.

A new methodology has been developed for the assessment of the annual effective dose resulting from removable and fixed radiological surface contamination. It is entitled SUDOQU (SUrface DOse QUantification) and it can for instance be used to derive criteria for surface contamination related to the import of non-food consumer goods, containers and conveyances, e.g., limiting values and operational screening levels. SUDOQU imposes mass (activity)-balance equations based on radioactive decay, removal and deposition processes in indoor and outdoor environments. This leads to time-dependent contamination levels that may be of particular importance in exposure scenarios dealing with one or a few contaminated items only (usually public exposure scenarios, therefore referred to as the 'consumer' model). Exposure scenarios with a continuous flow of freshly contaminated goods also fall within the scope of the methodology (typically occupational exposure scenarios, thus referred to as the 'worker model'). In this paper we describe SUDOQU, its applications, and its current limitations. First, we delineate the contamination issue, present the assumptions and explain the concepts. We describe the relevant removal, transfer, and deposition processes, and derive equations for the time evolution of the radiological surface-, air- and skin-contamination levels. These are then input for the subsequent evaluation of the annual effective dose with possible contributions from external gamma radiation, inhalation, secondary ingestion (indirect, from hand to mouth), skin contamination, direct ingestion and skin-contact exposure. The limiting effective surface dose is introduced for issues involving the conservatism of dose calculations. SUDOQU can be used by radiation-protection scientists/experts and policy makers in the field of e.g. emergency preparedness, trade and transport, exemption and clearance, waste management, and nuclear facilities. Several practical examples are worked out demonstrating the potential applications of the methodology.

Quantum yield for the photo-degradation of vitamin D3.

Ultraviolet radiation can photodegrade vitamin D3 to suprasterol I, superasterol II and 5,6-transvitamin D3. The probability of the photodegradation of vitamin D3, after the absorption of one photon, is called the quantum yield. We estimated the quantum yield ϕ for all the degeneration reactions together on the basis of the results reported by Webb et al. (1989) for a degradation experiment on pure, tritiated vitamin D3 in methanol in sunlight. We find ϕ = (0.42 ± 0.1). This value of the quantum yield can be used to estimate the kinetics contribution from vitamin D3 degradation in exposure experiments and model calculations.

The action spectrum for vitamin D3: initial skin reaction and prolonged exposure.

Vitamin D3 photosynthesis in the skin is formulated as a set of reaction equations, including side-reactions to lumisterol, tachysterol and toxisterols, and the accompanying reverse reactions, isomerisation of previtamin D3 to vitamin D3 and photodegradation of vitamin D3. The solution of this set is given for the stationary irradiance spectrum. The effective action spectrum for the instantaneous vitamin D3 production changes shape as a function of exposure, and therefore, no single action spectrum can be used. We assessed the action spectrum for unexposed skin and for skin that has been exposed to 7.5 Standard Erythemal Doses (SED). We constructed two new estimates: (1) the RIVM action spectrum, based on absorption spectra, quantum yields and skin transmission spectra, and (2) the modified QUT action spectrum, which is adjusted for self-absorption and skin transmission. For previously unexposed skin, the modified QUT action spectrum gives a qualitatively similar, but larger estimate than the RIVM action spectrum. We have not been able to solve the lack of quantitative agreement between the vitamin D production estimates from the three action spectrum estimates (RIVM, modified QUT and CIE). All new action spectra have stronger emphasis on the short wavelengths than the CIE action spectrum. We showed that, for wavelengths larger than 300 nm, the bandwidth that was used in the experiment that formed the basis of the CIE action spectrum, gives a red-shift of about 1 nm. Generally, with the formation of previtamin D3, the return reaction to provitamin D3 limits the production of vitamin D3. After some exposure, the new action spectrum has negative values for the longer wavelengths in the UVB. For the RIVM action spectrum, this happens after 7.5 SED, for the modified QUT action spectrum already after 1.25 SED, and after 7.5 SED the net production rate is largely cancelled. Thus prolonged exposure of previously unexposed skin saturates vitamin D3 formation. For maximum vitamin D production after 1.25 SED, sunscreens should block wavelengths larger than 310 nm. Sunscreens that block only UVB could result in reduction in vitamin D production after prolonged exposure, or even a destruction of vitamin D that has just been formed.

Detection of radioactivity of unknown origin: Protective actions based on inverse modelling.

The detection of radioactivity of unknown origin necessitates the use of models that can quantify unknown corresponding source term parameters. In this work, a method for solving this inverse problem is described. The main goal of the method is that it can be used in emergency response. Therefore, the full modelling chain dealing with the collection and pre-processing of measurement data, source term estimation, (forward) dispersion modelling, and consequence assessment are discussed. Firstly, to verify this inverse model SHERLOC, the part of the modelling chain concerning the source term estimation based on measurement data, is applied to the first episode of the European Tracer Experiment (ETEX). Secondly, the complete model chain is applied to a release that is still unaccounted for; the 106Ru measured in the atmosphere of Europe in September and October of 2017. It is estimated that during the night of the 25th to the 26th of September 2017 approximately 1.33 PBq (1.33×1015 Bq) of 106Ru was emitted at a location in the region of the Southern Urals in the Russian Federation. Statistical indicators show that the modelled levels of concentration are in good agreement with the measurements. The radiological consequences of the release are estimated to be minor at distances farther than 22 km from the estimated source. However, in the vicinity of the emission the maximum committed dose received by the public may have exceeded 100 mSv. Since the presented approach can be executed within few hours after the collection of measurement data it can be used in the emergency response following the detection of radioactivity of unknown origin.

Dark cyclobutane pyrimidine dimers are formed in the epidermis of Fitzpatrick skin types I/II and VI in vivo after exposure to solar-simulated radiation.

INTRODUCTION: Unlike "light" cylobutane pyrimidine dimers (CPD) formed during ultraviolet radiation (UVR) exposure, dark CPD (dCPD) are formed afterwards. Studies have attributed this to delayed melanin sensitization. There are no data on the role of melanin in dCPD formation in human skin. METHODS AND RESULTS: Volunteers of Fitzpatrick skin types (FST I/II vs. VI) were exposed to erythemally equivalent doses of solar simulated radiation. CPD were assessed by semi-quantitative immunostaining in whole epidermis and in three epidermal zones, and quantitative HPLC-MS/MS (whole epidermis) at different times post-exposure up to 24 hr. A CPD peak that appeared at 1-2 hr post-exposure in whole epidermis measurements, in all skin types, demonstrated dCPD. However, both dCPD and light CPD were absent in the basal layer of FST VI with the greatest melanin concentration. Modelling the whole epidermis data showed no differences between the repair kinetics of FST I/II and VI. DISCUSSION: Melanin may be a sensitizer or "sunscreen" for dCPD depending on its location and concentration. Previous CPD repair studies in human skin have assumed peak CPD immediately after UVR exposure and so have overestimated total repair.

Are the orthostatic fluid shifts to the calves augmented in autonomic failure?

BACKGROUND: In autonomic failure (AF), blood pressure (BP) falls upon standing which is commonly ascribed to defective vasoconstriction and excessive pooling. Observations on the amount of pooling in AF are contradictory. METHODS: We evaluated pooling using strain-gauge plethysmography (SGP) during head-up tilt (HUT) with a parachute harness fixed to the tilt table to avoid muscle tension in the lower limbs and thus to maximise pooling. 23 healthy subjects and 12 patients with AF were tilted for 5 min. BP and calf volume changes, as measured by SGP, were measured continuously. Multiple regression analysis was used to examine the effect of AF on orthostatic fluid shifts after adjustment for potential confounders. RESULTS: Patients did not differ from controls with respect to the increase of calf volume after 5 min HUT. The acute (0-1 min) and the prolonged (1-5 min) phases of calf volume responses to HUT were also similar between patients and controls. No correlation was found between the degree of orthostatic hypotension and the orthostatic calf volume change in AF. In one patient an additional measurement was made before rising from bed in the early morning demonstrating a greater albeit small increase of calf volume upon HUT. CONCLUSION: Orthostatic fluid shifts at the level of the calf in AF are not augmented during the course of the day despite marked hypotension. However, a small increase of pooling may be expected when the patient first gets out of bed in the morning probably due to the absence of oedema.

Assessment of orthostatic fluid shifts with strain gauge plethysmography.

We evaluated the use of strain gauge plethysmography (SGP) for the assessment of orthostatic fluid shifts during head up tilt (HUT). Subjects wore a parachute harness fixed to the tilt table to avoid muscle tension in the lower limbs during HUT. 22 Healthy subjects (9 women) were tilted for 5 minutes. Calf volume changes as measured by SGP, surface EMG, heart rate and blood pressure were measured continuously. Ten subjects underwent a second tilt test during which circulation in one leg was occluded with a pressure cuff at 250 mmHg. During HUT with occlusion, calf volume increased in the non-occluded leg by 1.9+/-0.3% (mean +/- SEM) and 0.2+/-0.2% in the occluded leg (p<0.001). During HUT without occlusion a significant correlation (r = 0.9) was found between measurements of the left and right leg with a mean difference of 0.03+/-0.1%. HUT did not cause significant changes of surface EMG. An unexpected gender effect was found: calf volume increased significantly more in men than in women. Men were significantly taller, but the hemodynamic response to HUT did not differ between both sexes. The gender effect on orthostatic increases of calf volume remained significant after adjustment for heart-to-calf distance. SGP during HUT with a parachute harness is a new, promising method to assess orthostatic fluid shifts. The gender differences in orthostatic pooling in the calf may be explained by a higher calf compliance in men together with a greater hydrostatic pressure due to a greater height in men.

A randomized study of the effect of carbonated water prior to myocardial SPECT.

OBJECTIVE: In myocardial perfusion single-photon emission computed tomography (SPECT), abdominal activity often interferes with the evaluation of perfusion in the inferior wall, especially after pharmacological stress. In this randomized study, we examined the effect of carbonated water intake versus still water intake on the quality of images obtained during myocardial perfusion images (MPI) studies. METHODS: A total of 467 MIBI studies were randomized into a carbonated water group and a water group. The presence of intestinal activity adjacent to the inferior wall was evaluated by two observers. Furthermore, a semi-quantitative analysis was performed in the adenosine subgroup, using a count ratio of the inferior myocardial wall and adjacent abdominal activity. RESULTS: The need for repeated SPECT in the adenosine studies was 5.3% in the carbonated water group versus 19.4% in the still water group (p = 0.019). The inferior wall-to-abdomen count ratio was significantly higher in the carbonated water group compared to the still water group (2.11 ± 1.00 vs. 1.72 ± 0.73, p < 0.001). The effect of carbonated water during rest and after exercise was not significant. CONCLUSIONS: This randomized study showed that carbonated water significantly reduced the interference of extra-cardiac activity in adenosine SPECT MPI.

Skin cancer risks avoided by the Montreal Protocol--worldwide modeling integrating coupled climate-chemistry models with a risk model for UV.

The assessment model for ultraviolet radiation and risk "AMOUR" is applied to output from two chemistry-climate models (CCMs). Results from the UK Chemistry and Aerosols CCM are used to quantify the worldwide skin cancer risk avoided by the Montreal Protocol and its amendments: by the year 2030, two million cases of skin cancer have been prevented yearly, which is 14% fewer skin cancer cases per year. In the "World Avoided," excess skin cancer incidence will continue to grow dramatically after 2030. Results from the CCM E39C-A are used to estimate skin cancer risk that had already been inevitably committed once ozone depletion was recognized: excess incidence will peak mid 21st century and then recover or even super-recover at the end of the century. When compared with a "No Depletion" scenario, with ozone undepleted and cloud characteristics as in the 1960s throughout, excess incidence (extra yearly cases skin cancer per million people) of the "Full Compliance with Montreal Protocol" scenario is in the ranges: New Zealand: 100-150, Congo: -10-0, Patagonia: 20-50, Western Europe: 30-40, China: 90-120, South-West USA: 80-110, Mediterranean: 90-100 and North-East Australia: 170-200. This is up to 4% of total local incidence in the Full Compliance scenario in the peak year.

Spatial- and time-explicit human damage modeling of ozone depleting substances in life cycle impact assessment.

Depletion of the stratospheric ozone layer is mainly caused by emissions of persistent halocarbons of anthropogenic origin. The resulting increase of solar ultraviolet radiation at the Earth's surface is associated with increased exposure of humans and increased human health damage. Here we assessed the change in human health damage caused by three types of skin cancer and cataract in terms of (healthy) years of life lost per kiloton emission reduction of an ozone-depleting substance (ODS). This so-called characterization factor is used in Life Cycle Assessments (LCAs). Characterization factors are provided for the emissions of five chlorofluorocarbons, three hydrochlorofluorocarbons, three (bromine-containing) halons, carbon tetrachloride, methyl chloroform, and anthropogenic emissions of methyl bromide. We employed dynamic calculations on a global scale for this purpose, taking physical and social geographic data into account such as skin tones, population density, average age, and life expectancy. When emission rates of all ODSs in 2007 are multiplied by our characterization factors, the resulting number of years of life lost may be a factor of 5 higher than reported previously. This increase is merely explained through the global demographic development until 2100 we took into account.