Avoidable mortality from giving tranexamic acid to bleeding trauma patients: an estimation based on WHO mortality data, a systematic literature review and data from the CRASH-2 trial

BACKGROUND: The CRASH-2 trial showed that early administration of tranexamic acid (TXA) safely reduces mortality in bleeding in trauma patients. Based on data from the CRASH-2 trial, global mortality data and a systematic literature review, we estimated the number of premature deaths that might be averted every year worldwide through the use of TXA. METHODS: We used CRASH-2 trial data to examine the effect of TXA on death due to bleeding by geographical region. We used WHO mortality data (2008) and data from a systematic review of the literature to estimate the annual number of in-hospital trauma deaths due to bleeding. We then used the relative risk estimates from the CRASH-2 trial to estimate the number of premature deaths that could be averted if all hospitalised bleeding trauma patients received TXA within one hour of injury, and within three hours of injury. Sensitivity analyses were used to explore the effect of uncertainty in the parameter estimates and the assumptions made in the model. RESULTS: There is no evidence that the effect of TXA on death due to bleeding varies by geographical region (heterogeneity p = 0.70). Based on WHO data and our systematic literature review, we estimate that each year worldwide there are approximately 400,000 in-hospital trauma deaths due to bleeding. If patients received TXA within one hour of injury then approximately 128,000 (uncertainty range [UR] ≈ 72,000 to 172,000) deaths might be averted. If patients received TXA within three hours of injury then approximately 112,000 (UR ≈ 68,000 to 148,000) deaths might be averted. Country specific estimates show that the largest numbers of deaths averted would be in India and China. CONCLUSIONS: The use of TXA in the treatment of traumatic bleeding has the potential to prevent many premature deaths every year. A large proportion of the potential health gains are in low and middle income countries

DSYB catalyses the key step of dimethylsulfoniopropionate biosynthesis in many phytoplankton

Dimethylsulfoniopropionate (DMSP) is a globally important organosulfur molecule and the major precursor for dimethyl sulfide. These compounds are important info-chemicals, key nutrients for marine microorganisms, and are involved in global sulfur cycling, atmospheric chemistry and cloud formation1,2,3. DMSP production was thought to be confined to eukaryotes, but heterotrophic bacteria can also produce DMSP through the pathway used by most phytoplankton4, and the DsyB enzyme catalysing the key step of this pathway in bacteria was recently identified5. However, eukaryotic phytoplankton probably produce most of Earth’s DMSP, yet no DMSP biosynthesis genes have been identified in any such organisms. Here we identify functional dsyB homologues, termed DSYB, in many phytoplankton and corals. DSYB is a methylthiohydroxybutryate methyltransferase enzyme localized in the chloroplasts and mitochondria of the haptophyte Prymnesium parvum, and stable isotope tracking experiments support these organelles as sites of DMSP synthesis. DSYB transcription levels increased with DMSP concentrations in different phytoplankton and were indicative of intracellular DMSP. Identification of the eukaryotic DSYB sequences, along with bacterial dsyB, provides the first molecular tools to predict the relative contributions of eukaryotes and prokaryotes to global DMSP production. Furthermore, evolutionary analysis suggests that eukaryotic DSYB originated in bacteria and was passed to eukaryotes early in their evolution

Insights into the Molecular Mechanisms of the Anti-Atherogenic Actions of Flavonoids in Normal and Obese Mice

Obesity is a major and independent risk factor for cardiovascular disease and it is strongly associated with the development of dyslipidemia, insulin resistance and type 2 diabetes. Flavonoids, a diverse group of polyphenol compounds of plant origin widely distributed in human diet, have been reported to have numerous health benefits, although the mechanisms underlying these effects have remained obscure. We analyzed the effects of chronic dietary supplementation with flavonoids extracted from cranberry (FLS) in normal and obese C57/BL6 mice compared to mice maintained on the same diets lacking FLS. Obese mice supplemented with flavonoids showed an amelioration of insulin resistance and plasma lipid profile, and a reduction of visceral fat mass. We provide evidence that the adiponectin-AMPK pathway is the main mediator of the improvement of these metabolic disorders. In contrast, the reduced plasma atherogenic cholesterol observed in normal mice under FLS seems to be due to a downregulation of the hepatic cholesterol synthesis pathway. Overall, we demonstrate for the first time that the molecular mechanisms underlying the beneficial effects of flavonoids are determined by the metabolic state

Staff recruitment, development and global mobility

This paper considers issues that relate to staff recruitment, staff development and global mobility of dental academics. Published literature, which has a North American bias, is reviewed. Recommendations, which may be applicable world-wide, are made to address evident and pertinent areas of concern in terms of the availability of quality dental teaching staff in dental teaching institutions so as to sustain the global dental academic enterprise at appropriately high levels of achievement. © 2008 Blackwell Munksgaard and The American Dental Education Association.link_to_subscribed_fulltex

A comparison of mandibular and maxillary alveolar osteogenesis over six weeks: a radiological examination

INTRODUCTION : Insufficient information exists on comparing radiological differences in bone density of the regeneration rate in the alveolar bone of the maxilla and mandible following the creation of similar defects in both. METHODS : Alveolar bone defects were created from five healthy Chacma baboons. Standardized x-ray images were acquired over time and the densities of the selected defect areas were measured pre-operatively, directly post-operatively and at three- and six weeks post-operatively. Differences in densities were statistically tested using ANOVA. RESULTS : The maxilla was significantly more radiologically dense (p = 0.026) than the mandible pre- operatively. No differences were obtained between the maxilla and mandible directly postoperatively and three- and six weeks post-operatively respectively; i.e. densities were not significantly different at the different time points after the defects had been created (three weeks: t = 1.08, p = 0.30; six weeks: t = 1.35, p = 0.19; three to six weeks: t = 1.20, p =0.25). The increase in density in the mandible was 106% (8.9±7.6%/time versus 4.3 ± 2.7%/time) over three weeks, 28% (15.0 ± 8.1%/time versus 11.7 ± 8.0%/time) over six weeks and 56% (12.5 ± 9.7%/time versus 8.0 ± 6.9%/time) over three-to-six weeks and was higher than in the maxilla over the same intervals. CONCLUSIONS : Radiological examination with its standardized gray-scale analysis can be used to determine the difference in bone density of the maxilla and mandible. Although not statistically significant, the mandible healed at a faster rate than the maxilla, especially observed during the first three weeks after the defects were created.http://www.head-face-med.com/hb201