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/     

Effect of electronic homeopathic copy of biohumus fertilizer on tomato sprout development

Electronic homeopathic copies (EHC) are remedies prepared without traditional dilution/potentiation but by means of so-called "imprinting" of initial substance to water (or other carriers) with the help of M. Ray's devices. EHC are interpreted by modern homeopathic medicine as functional analogs of biologically active substances (BAS) in supersmall doses (SSD). The authors have undertaken 3 blind randomised experiments concerning BAS aqueous solution of fertilizer biohumus, its EHC and placebo influence on tomatoes' sprouts development. Filtered and intermixed water have been encapsulated in 1.5-liter polyethylene containers. The solution of fertilizer has been prepared in accordance with the instruction. EHC has been "transferred" from the concentrated fertilizer with the help of Simulator (Metabolics, GB) apparatus. "Deleting" of information have been made for placebo. Seed of tomatoes (kind "Yasniye") have been pre-soaked in preparations and landed in accordingly numbered plastic boxes (97 x 15 x 14 sm) by 40-44 plants in each one. The seedbed was from one well intermixed portion. The plants were top-dressed by preparations (200-300 ml) one time per week. The boxes were exposed in one room (rotation was made twice per week). The plants have been cut up on the 38th day from pre-soaking. The height of a green part and its mass have been measured for each plant. The differences between independent samples (preparations studied) have been estimated. The differences between EHC and placebo have appeared to be reliable, in the first experiment (p < 2 x 10(-4)--mass, p < 10(-9)--height), in the second one (p = 0.014--mass), in the third one (p < 3 x 10(-6)--mass, p = 0.028--height) The results obtained verify a reality of EHC phenomenon. Thus it is quite within reason to suggest an existence of uniform physical (instead of chemical) mechanism of BAS's EHC/SSD structuring and acting on biological objects.     

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      

Duration of tracheal sound recorded during forced expiration: From a model to establishing standards

Analysis of the duration of tracheal sound recorded during forced expiration (TSFE) was performed to detect bronchial conductance disorders and to develop a method for establishing individually tailored standards. A standard individual duration of the TSFE served as an estimate of the relevant expiratory resistance of the bronchial tree in healthy subjects and showed the extent to which sound duration exceeded that predicted from the normal individual resistance in flow-limited subjects.     

Hatching asynchrony and brood reduction influence immune response in Common Kestrel Falco tinnunculus nestlings

The onset of incubation before the end of laying imposes asynchrony at hatching and, therefore, a size hierarchy in the brood. It has been argued that hatching asynchrony might be a strategy to improve reproductive output in terms of quality or quantity of offspring. However, little is known about the mediating effect of hatching asynchrony on offspring quality when brood reduction occurs. Here, we investigate the relationship between phenotypic quality and hatching asynchrony in Common Kestrel Falco tinnunculus nestlings in Spain. Hatching asynchrony did not increase breeding success or nestling quality. Furthermore, hatching asynchrony and brood reduction had different effects on nestlings’ phytohaematogglutinin (PHA)‐mediated immune response and nestling growth. In asynchronous and reduced broods (in which at least one nestling died), nestlings showed a stronger PHA‐mediated immune response and tended to have a smaller body size compared with nestlings raised in synchronous and reduced broods. When brood reduction occurred in broods hatched synchronously, there was no effect on nestling size, but nestlings had a relatively poor PHA‐mediated immune response compared with nestlings raised in asynchronous and reduced broods. We suggest that resources for growth can be directed to immune function only in asynchronously hatched broods, resulting in improved nestling quality, as suggested by their immune response. We also found that males produced a greater PHA‐mediated immune response than females only in brood‐reduced nests without any effect on nestling size or condition, suggesting that females may trade off immune activities and body condition, size or weight. Overall, our results suggest that hatching pattern and brood reduction may mediate resource allocation to different fitness traits. They also highlight that the resolution of immune‐related trade‐offs when brood reduction occurs may differ between male and female nestlings.     

Risk Factors for Death in 632 Patients with Sickle Cell Disease in the United States and United Kingdom

Background

The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial.

Methods and Results

We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)≥3.0 m/s cuttof, which has a 67–75% positive predictive value for mean pulmonary artery pressure ≥25 mm Hg was used. Among 572 subjects, 11.2% had TRV≥3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV≥3.0 m/sec. At 24 months the cumulative survival was 83% with TRV≥3.0 m/sec and 98% with TRV<3.0 m/sec (p<0.0001). The hazard ratios for death were 11.1 (95% CI 4.1–30.1; p<0.0001) for TRV≥3.0 m/sec, 4.6 (1.8–11.3; p = 0.001) for NT-proBNP≥160 pg/mL, and 14.9 (5.5–39.9; p<0.0001) for both TRV≥3.0 m/sec and NT-proBNP≥160 pg/mL. Age >47 years, male gender, chronic transfusions, WHO class III–IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death.

Conclusions

A TRV≥3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable.

The study is registered in ClinicalTrials.gov with identifier

{"type":"clinical-trial","attrs":{"text":"NCT00492531","term_id":"NCT00492531"}}NCT00492531     

Fine‐scale bird monitoring from light unmanned aircraft systems

Unmanned aircraft systems (UAS) are remote‐controlled devices capable of collecting information from difficult‐to‐access places while minimizing disturbance. Although UAS are increasingly used in many research disciplines, their application to wildlife research remains to be explored in depth. Here, we report on the use of a small UAS to monitor temporal changes in breeding population size in a Black‐headed Gull Chroicocephalus ridibundus colony. This method makes it possible to obtain georeferenced data on nest locations without causing colony disturbance, which would not otherwise be possible via direct ground observations.     

Significance of Spectral and Time Parameters of Forced Expiratory Sound in Evaluating Bronchial Patency

Spectral and time characteristics of forced expiratory sound, recorded in the trachea, were analyzed in 96 subjects. Sick and healthy subjects and the risk group demonstrated substantial differences in the acoustic parameters (total sound duration, vortex stoppage duration, and emergence of spectral components with high frequency and narrow band at the end of an expiration). The authors suggest and substantiate acoustic criteria of the bronchial patency disorder, assuming on this basis that such disorders are more common in patients with chronic nonobstructive bronchitis (70.8%) and subjects at risk for chronic obstructive pulmonary diseases (45.4%) than is demonstrated by conventional functional methods.