Severe Painful Vaso-Occlusive Crises and Mortality in a Contemporary Adult Sickle Cell Anemia Cohort Study

Background

Frequent painful vaso-occlusive crises (VOCs) were associated with mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) over twenty years ago. Modern therapies for sickle cell anemia (SCA) like hydroxyurea are believed to have improved overall patient survival. The current study sought to determine the relevance of the association between more frequent VOCs and death and its relative impact upon overall mortality compared to other known risk factors in a contemporary adult SCA cohort.

Methods

Two hundred sixty four SCA adults were assigned into two groups based on patient reported outcomes for emergency department (ED) visits or hospitalizations for painful VOC treatment during the 12 months prior to evaluation.

Results

Higher baseline hematocrit (p = 0.0008), ferritin (p = 0.005), and HDL cholesterol (p = 0.01) were independently associated with 1 or more painful VOCs requiring an ED visit or hospitalization for acute pain. During a median follow-up of 5 years, mortality was higher in the ED visit/hospitalization group (relative risk [RR] 2.68, 95% CI 1.1-6.5, p = 0.03). Higher tricuspid regurgitatant jet velocity (TRV) (RR 2.41, 95% CI 1.5-3.9, p < 0.0001), elevated ferritin (RR 4.00, 95% CI 1.8-9.0, p = 0.001) and lower glomerular filtration rate (RR=2.73, 95% CI 1.6-4.6, p < 0.0001) were also independent risk factors for mortality.

Conclusions

Severe painful VOCs remain a marker for SCA disease severity and premature mortality in a modern cohort along with other known risk factors for death including high TRV, high ferritin and lower renal function. The number of patient reported pain crises requiring healthcare utilization is an easily obtained outcome that could help to identify high risk patients for disease modifying therapies.

Trial Registration

ClinicalTrials.gov NCT00011648 http://clinicaltrials.gov/     

Evaluation of the Effect of Light Intensity on the Measurement of the Photosynthetic Rate in Plankton Microalgae by the Chlorophyll Fluorescence Method

The use of relative variable fluorescence (RVF) of chlorophyll, as measured in the presence of Diuron, an inhibitor of electron transfer, for the estimation of the photosynthetic activity of plankton microalgae was analyzed under a wide range of light intensities in the PAR region. Oxygen evolution rates (estimated by the method of light and dark bottles and the amperometric method), RVF, and chlorophyll a concentration were measured in parallel in natural algal cenoses and microecosystems. When the previously used regression equation, in the form A = b(F/F _d)C _chl I, where A is O₂ evolution rate (g/(m³ h), F/F _d is RVF (relative units), C _chl is chlorophyll a concentration (mg/m³), and I is light intensity (W/m²), was verified in the PAR region, we observed a nonlinear dependence of the correction coefficient b on I, which can be described by the formula b = 6.227 × 10³I. This result agrees with the hypothesis that chlorophyll a fluorescence quenching comprises photochemical (qQ) and energy (qE) components. On the basis of the energy model, we determined the upper limit b _max = 0.003 for light intensity range I< 4.4 W/m² and the lower limit b _min = 0.0003 for I = 400 W/m².     

Effects of medium viscosity on kinetics of the enzymatic reaction catalyzed by bacterial RNase

Effects of medium viscosity on kinetic parameters of poly(U) hydrolysis catalyzed by RNase from Bac. intermedius 7P (binase) were studied in solutions of sucrose (4-50 wt. %) and glycerol (35-62 wt. %) in Tris--sodium acetate buffer (pH 7.5) at 25 degreesC. The rate constant of reaction kcat was practically unchanged over a wide range of viscosities (1-15 cP for sucrose and 2.5-3 cP for glycerol). In glycerol solutions, kcat slightly increased with viscosity increase from 4 to 10 cP. Addition of NaCl to the buffer medium resulted in an inhibitory effect of Na+ on kcat, prevented by 50% sucrose or 60% glycerol. It is concluded that binase-catalyzed poly(U) cleavage occurs through a "tense"-substrate mechanism, similarly to reactions catalyzed by alpha-chymotrypsin, trypsin, and laccase.     

A web server to locate periodicities in a sequence

Summary : FT is a tool written in C++, which implements the Fourier analysis method to locate periodicities in aminoacid or DNA sequences. It is provided for free public use on a WWW server with a Java interface. Availability : The server address is http://o2.db. uoa.gr/FT Contact : shamodr@atlas.uoa.gr      

Characteristics of common wheat cultivars of West Siberia carrying the wheat-rye 1RS.1BL translocation

Using genomic in situ hybidization, among the common wheat cultivars produced in West Siberia (Siberian Research Institute of Agriculture, Omsk) with the involvement of the winter wheat cultivar Kavkaz carrying the wheat-rye 1RS.1BL translocation we identified three cultivars with this translocation: Omskaya 29, Omskaya 37, and Omskaya 38. The protein and crude gluten contents in the grain of these cultivars are equal to or exceed the levels observed in cultivars without the wheat-rye translocation. The common wheat cultivars carrying the wheat-rye translocation were evaluated in terms of resistance of plants reaching wax ripeness to leaf rust and powdery mildew in the natural field conditions. The cultivars Omskaya 37 and Omskaya 38 displayed a high field resistance to leaf rust and were resistant to a variable extent to powdery mildew. The cultivar Omskaya 29 was susceptible to leaf rust and powdery mildew pathogens. Importance of the selection direction and the role of the genetic background in developing common wheat cultivars carrying the wheat-rye translocation is discussed.     

Masked red-emitting carbopyronine dyes with photosensitive 2-diazo-1-indanone caging group

Caged near-IR emitting fluorescent dyes are in high demand in optical microscopy but up to now were unavailable. We discovered that the combination of a carbopyronine dye core and a photosensitive 2-diazo-1-indanone residue leads to masked near-IR emitting fluorescent dyes. Illumination of these caged dyes with either UV or visible light (λ < 420 nm) efficiently generates fluorescent compounds with absorption and emission at 635 nm and 660 nm, respectively. A high-yielding synthetic route with attractive possibilities for further dye design is described in detail. Good photostability, high contrast, and a large fluorescence quantum yield after uncaging are the most important features of the new compounds for non-invasive imaging in high-resolution optical microscopy. For use in immunolabelling the caged dyes were decorated with a (hydrophilic) linker and an (activated) carboxyl group.     

Estimation of periphytic microalgae gross primary production with DCMU-fluorescence method in Yenisei River (Siberia, Russia)

Periphyton (epilithon) gross primary production (GPP) was estimated using the DCMU-fluorescence method in the Yenisei River. In the unshaded littoral zone, chlorophyll a concentration (Chl a) and GPP value varied from 0.83 to 973.74 mg m⁻²and 2–304,425 O₂ m⁻² day⁻¹ (0.64–95 133 mg C m⁻² day⁻¹), respectively. Positive significant correlation (r = 0.8) between daily GPP and periphyton Chl a was found. Average ratio GPP:Chl a for periphyton was 36.36 mg C mg Chl a m⁻² day⁻¹. The obtained GPP values for the Yenisei River have a high significant correlation with values predicted by a conventional empirical model for stream periphyton. We concluded that the DCMU-fluorescence method can be successfully used for measuring of gross primary production of stream phytoperiphyton at least as another useful tool for such studies.     

Comparative Analysis of Content of Omega-3 Polyunsaturated Fatty Acids in Food and Muscle Tissue of Fish from Aquaculture and Natural Habitats

Two fish species reared in aquaculture (pink salmon Oncorhynchus gorbuscha and whitefish Coregonus lavaretus) and ten fish species from natural habitats (whitefish C. lavaretus, tugun Coregonus tugun, broad whitefish Coregonus nasus, least cisco Coregonus sardinella, vendace Coregonus albula, boganid charr Salvelinus boganidae, charr Salvelinus alpinus complex, northern pike Esox lucius, sharp-snouted lenok Brachymystax lenok, and taimen Hucho taimen) have been studied. The content of two long-chain polyunsaturated omega-3 fatty acids (PUFAs), eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), in the muscle tissue of the fish and in their food (intestine contents) are compared. In the aquacultures of whitefish and pink salmon, the total content of EPA and DHA is significantly higher in feed than in the muscle tissue of the fish, which indicates losses of PUFA in the two-link food chain of the aquaculture during their transfer to the upper trophic level. EPA and DHA losses in aquaculture, which are confirmed by numerous literature data, mean an inefficient usage of the available sources of PUFAs and the aggravation of the global deficit of these biochemicals in the human diet. A study of natural fish populations reveals the accumulation of EPA and DHA in their biomass compared to food in many cases, although opposite phenomena are also observed. An assumption on the presence of an optimal, physiologically adequate species-specific level of PUFA in the fish muscle tissue has been made based on our data and literature data. If the level of PUFAs in the muscles is lower than optimal, their accumulation (bioaccumulation) from food and/or de novo synthesis are observed. When the optimal level is exceeded, the content of EPA and DHA in biomass approaches maximum species-specific values; however, part of these PUFAs entering from food is not digested or is catabolized. According to the obtained data, the species of the order Salmoniformes have an optimal level of 2 to 6 mg/g of wet weight. It has been found that in aquaculture approaching to maximum values of EPA + DHA content was accompanied by their losses (scattering) in the food chains, while in natural ecosystems the maximum values of PUFA content in the fish biomass are achieved by their accumulation from the lower trophic level. Boganid charr S. boganidae had the highest content of EPA + DHA in the muscle tissue among all known fish species (32.78 mg/g of wet weight).     

Selective grazing on Cryptomonas by Ceriodaphnia quadrangula fed a natural phytoplankton assemblage

Grazing of C. quadrangula from a Siberian forest pond on natural phytoplankton assemblages was studied in a modified flow-through system. Ceriodaphniastrongly selected subdominant Cryptomonas erosarather than the dominant diatoms of comparable size. Using Cryptomonas as the sole microalgae food, Ceriodaphnia demonstrated significant somatic and population growth. Seasonal biomass maximum of Ceriodaphnia and Cryptomonas coincidedin the pond. Although bacterial component cannot be excluded, it was concluded that Cryptomonaswas the principal algal food source for Ceriodaphnia.