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

The chemokine receptor CXCR5 is pivotal for ectopic mucosa-associated lymphoid tissue neogenesis in chronic Helicobacter pylori-induced inflammation

Ectopic lymphoid follicles are a key feature of chronic inflammatory autoimmune and infectious diseases, such as rheumatoid arthritis, Sjögren's syndrome, and Helicobacter pylori-induced gastritis. Homeostatic chemokines are considered to be involved in the formation of such tertiary lymphoid tissue. High expression of CXCL13 and its receptor, CXCR5, has been associated with the formation of ectopic lymphoid follicles in chronic infectious diseases. Here, we defined the role of CXCR5 in the development of mucosal tertiary lymphoid tissue and gastric inflammation in a mouse model of chronic H. pylori infection. CXCR5-deficient mice failed to develop organized gastric lymphoid follicles despite similar bacterial colonization density as infected wild-type mice. CXCR5 deficiency altered Th17 responses but not Th1-type cellular immune responses to H. pylori infection. Furthermore, CXCR5-deficient mice exhibited lower H. pylori-specific serum IgG and IgA levels and an overall decrease in chronic gastric immune responses. In conclusion, the development of mucosal tertiary ectopic follicles during chronic H. pylori infection is strongly dependent on the CXCL13/CXCR5 signaling axis, and lack of de novo lymphoid tissue formation attenuates chronic immune responses

Application of 3D Printing for Smart Objects with Embedded Electronic Sensors and Systems

Applications of a 3D printing process are presented. This process integrates liquid-state printed components and interconnects with IC chips in all three dimensions, various orientations, and multiple printing layers to deliver personalized system-level functionalities. As an example application, a form-fitting glove is demonstrated with embedded programmable heater, temperature sensor, and the associated control electronics for thermotherapeutic treatment

Reaction of N,N’-dimethylformamide and divalent viologen molecule to generate an organic dopant for molybdenum disulfide

Tuning the carrier concentration is essential for semiconducting materials to apply optoelectronic devices. Molybdenum disulfide (MoS2) is a semiconducting material composed of atomically thin (∼0.7 nm thickness) layers. To dope thin MoS2, instead of using conventional atom/ion injection processes, a surface charge transfer method was successfully applied. In this study, we report a simple preparation method of a molecular dopant applicable to the doping process. The method follows a previous report for producing a molecular dopant, benzyl viologen (BV) which shows electron doping to MoS2. To prepare dopant BV molecules, a reduction process with a commercially available divalent BV by sodium borohydride (NaBH4) is required; however, the reaction requires a large consumption of NaBH4. NaBH4 drastically reacts with the solvent water itself. We found a reaction process of BV in an organic solvent, N,N’-dimethylformamide (DMF), by adding a small amount of water dissolving the divalent BV. The reaction is mild (at room temperature) and is autonomous once DMF comes into contact with the divalent BV aqueous solution. The reaction can be monitored with a UV-Vis spectrometer, and kinetic analysis indicates two reaction steps between divalent/monovalent/neutral viologen isomers. The product was soluble in toluene and did not dissolve in water, indicating it is similar to the reported dopant BV. The synthesized molecule was found to act as a dopant for MoS2 by applying a metal-oxide-semiconductor field-effect-transistor (MOSFET) structure. The process is a general method and applicable to other viologen-related dopants to tune the electronic structure of 2D materials to facilitate generating atomically thin devices

Oriented Growth of Gold Nanowires on MoS2

Layered 2D materials serve as a new class of substrates for templated synthesis of various nanomaterials even with highly dissimilar crystal structures; thus overcoming the lattice constraints of conventional epitaxial processes. Here, molybdenum disulfide (MoS2) is used as a prototypical model substrate for oriented growth of in-plane Au nanowires (NWs) despite the nearly 8% lattice mismatch between MoS2 and Au. Au NWs on the MoS2 surface are oriented along three symmetrically equivalent directions within the substrate arising from the strong Au-S binding that templates the oriented growth. The kinetics of the growth process are explored through experiments and modeling. Strong charge transfer is observed between Au NWs and MoS2, resulting in degenerate p-doping of MoS2

Oriented Growth of Gold Nanowires on MoS2

Layered 2D materials serve as a new class of substrates for templated synthesis of various nanomaterials even with highly dissimilar crystal structures; thus overcoming the lattice constraints of conventional epitaxial processes. Here, molybdenum disulfide (MoS2) is used as a prototypical model substrate for oriented growth of in-plane Au nanowires (NWs) despite the nearly 8% lattice mismatch between MoS2 and Au. Au NWs on the MoS2 surface are oriented along three symmetrically equivalent directions within the substrate arising from the strong Au-S binding that templates the oriented growth. The kinetics of the growth process are explored through experiments and modeling. Strong charge transfer is observed between Au NWs and MoS2, resulting in degenerate p-doping of MoS2

Gastric mucosal hyperplasia via upregulation of gastrin induced by persistent activation of gastric innate immunity in major histocompatibility complex class II deficient mice

BACKGROUND AND AIM: Major histocompatibility complex class II deficient (Aα(0/0)) mice have decreased CD4(+) T cells, making them immunologically similar to patients with acquired immunodeficiency syndrome (AIDS). Both patients with AIDS and Aα(0/0) mice have hypertrophic gastric folds. To clarify the mechanism of gastric mucosal hyperplasia, we investigated the pathophysiology and the role of the innate immunity in the stomach of Aα(0/0) mice. METHODS: Stomachs from 1–6 month old Aα(0/0) mice, kept under specific pathogen free conditions, were examined at 1 month intervals histologically and immunohistochemically. Gene expression of proinflammatory cytokines, Toll‐like receptors (TLRs), cyclooxygenase (COX)‐2, and myeloperoxidase (MPO) activity in the gastric mucosa was investigated. Serum gastrin levels and gastric acidity were measured. Bacterial culture of the stomach was performed. To clarify the roles of hypergastrinaemia in the gastric mucosa, a gastrin receptor antagonist (AG041R) was administered. RESULTS: Aα(0/0) mice had a diffusely thick corpus mucosa with infiltration of CD11b(+) granulocytes and macrophages. Anti‐Ki67 staining demonstrated expansion of the proliferating neck zone. Gene expression of interleukin 1β, interferon γ, TLR‐2, TLR‐4, and COX‐2 were upregulated, and MPO activity was increased. Only a small amount of non‐pathogenic bacteria was detected in the stomach. Serum gastrin levels and Reg‐Iα positive cells in the gastric mucosa increased, despite normal gastric acidity. After treatment with AG041R, gastric mucosal thickness was significantly reduced. CONCLUSION: Persistent activation of innate immunity in the stomach induced gastric mucosal hyperplasia through upregulation of gastrin synthesis in Aα(0/0) mice, suggesting a pathophysiology similar to the gastric changes in patients with AIDS