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1.
Kaspars Maleckis Eric Anttila Paul Aylward William Poulson Anastasia Desyatova Jason MacTaggart Alexey Kamenskiy 《Annals of biomedical engineering》2018,46(5):684-704
Endovascular stenting has matured into a commonly used treatment for peripheral arterial disease (PAD) due to its minimally invasive nature and associated reductions in short-term morbidity and mortality. The mechanical properties of the superelastic Nitinol alloy have played a major role in the explosion of peripheral artery stenting, with modern stents demonstrating reasonable resilience and durability. Yet in the superficial femoral and popliteal arteries, even the newest generation Nitinol stents continue to demonstrate clinical outcomes that leave significant room for improvement. Restenosis and progression of native arterial disease often lead to recurrence of symptoms and reinterventions that increase morbidity and health care expenditures. One of the main factors thought to be associated with stent failure in the femoropopliteal artery (FPA) is the unique and highly dynamic mechanical environment of the lower limb. Clinical and experimental data demonstrate that the FPA undergoes significant deformations with limb flexion. It is hypothesized that the inability of many existing stent designs to conform to these deformations likely plays a role in reconstruction failure, as repetitive movements of the leg and thigh combine with mechanical mismatch between the artery and the stent and result in mechanical damage to both the artery and the stent. In this review we will identify challenges and provide a mechanical perspective of FPA stenting, and then discuss current research directions with promise to provide a better understanding of Nitinol, specific features of stent design, and improved characterization of the biomechanical environment of the FPA to facilitate development of better stents for patients with PAD. 相似文献
2.
Non-covalent intermolecular interactions between pyridinium subunits in a crystal-state are an efficient means to accomplish aggregation induced emission and avoid aggregation caused quenching.Non-covalent intermolecular pyridinium–pyridinium and pyridinium–arene-π system interactions result in aggregation induced emission (AIE). 相似文献
3.
Nimalan Arinaminpathy Thierry Cordier-Lassalle Kaspars Lunte Christopher Dye 《Bulletin of the World Health Organization》2015,93(4):237-248A
Objective
To investigate funding for the Global Drug Facility since 2001 and to analyse the facility’s influence on the price of high-quality tuberculosis drugs.Methods
Data on the price of tuberculosis drugs were obtained from the Global Drug Facility for 2001 to 2012 and, for the private sector in 15 countries, from IMS Health for 2002 to 2012. Data on funding of the facility were also collected.Findings
Quality-assured tuberculosis drugs supplied by the Global Drug Facility were generally priced lower than drugs purchased in the private sector. In 2012, just three manufacturers accounted for 29.9 million United Stated dollars (US$) of US$ 44.5 million by value of first-line drugs supplied. The Global Fund to Fight AIDS, Tuberculosis and Malaria provided 73% (US$ 32.5 million of US$ 44.5 million) and 89% (US$ 57.8 million of US $65.2 million) of funds for first- and second-line drugs, respectively. Between 2010 and 2012, the facility’s market share of second-line tuberculosis drugs increased from 26.1% to 42.9%, while prices decreased by as much as 24% (from US$ 1231 to US$ 939). Conversely, the facility’s market share of first-line drugs fell from 37.2% to 19.2% during this time, while prices increased from US$ 9.53 to US$ 10.2.Conclusion
The price of tuberculosis drugs supplied through the facility was generally less than that on the private market. However, to realize its full potential and meet the needs of more tuberculosis patients, the facility requires more diverse and stable public funding and greater flexibility to participate in the private market. 相似文献4.
The crystal structure of the sobemovirus Ryegrass mottle virus (RGMoV) has been determined at 2.9 A resolution. The coat protein has a canonical jellyroll beta-sandwich fold. In comparison to other sobemoviruses the RGMoV coat protein is missing several residues in two of the loop regions. The first loop contributes to contacts between subunits around the quasi-threefold symmetry axis. The altered contact interface results in tilting of the subunits towards the quasi-threefold axis. The assembly of the T=3 capsid of sobemoviruses is controlled by the N-termini of C subunits forming a so-called beta-annulus. The other loop that is smaller in the RGMoV structure contains a helix that participates in stabilization of the beta-annulus in other sobemoviruses. The loss of interaction between the RGMoV loop and the beta-annulus has been compensated for by additional interactions between the N-terminal arms. As a consequence of these differences, the diameter of the RGMoV particle is 8 A smaller than that of the other sobemoviruses. The interactions of coat proteins in sobemovirus capsids involve calcium ions. Depletion of calcium ions results in particle swelling, which is considered a first step in disassembly. We could not identify any density for metal ions in the proximity of the conserved residues normally involved in calcium binding, but the RGMoV structure does not show any signs of swelling. A likely reason is the low pH (3.0) of the crystallization buffer in which the groups interacting with the calcium ions are not charged. 相似文献
5.
Guntars Pupelis Vladimir Fokin Kaspars Zeiza Haralds Plaudis Anastasija Suhova Nadezda Drozdova Viesturs Boka 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2013,15(7):535-540
Background
The control of sepsis is the primary goal of surgical intervention in patients with infected necrosis. Simple surgical approaches that are easy to reproduce may improve outcomes when specialists in endoscopy are not available. The aim of the present study was to describe the experience with a focused open necrosectomy (FON) in patients with infected necrosis.Method
A prospective pilot study conducted to compare a semi-open/closed drainage laparotomy and FON with the assistance of peri-operative ultrasound. The incidence of sepsis, dynamics of C-reactive protein (CRP), intensive care unit (ICU)/hospital stay, complication rate and mortality were compared and analysed.Results
From a total of 58 patients, 36 patients underwent a conventional open necrosectomy and 22 patients underwent FON. The latter method resulted in a faster resolution of sepsis and a significant decrease in mean CRP on Day 3 after FON, P = 0.001. Post-operative bleeding was in 1 versus 7 patients and the incidence of intestinal and pancreatic fistula was 2 versus 8 patients when comparing FON to the conventional approach. The median ICU stay was 11.6 versus 23 days and the hospital stay was significantly shorter, 57 versus 72 days, P = 0.024 when comparing FON versus the conventional group. One patient died in the FON group and seven patients died in the laparotomy group, P = 0.139.Discussion
FON can be an alternative method to conventional open necrosectomy in patients with infected necrosis and unresolved sepsis. 相似文献6.
Protonation of pyridines with a strong acid is a general and straightforward approach to achieve efficient aggregation induced emission (AIE) in structurally remarkably simple organic molecules that lack any of the conventional luminophores. The relationship between the nature of counter ion and the AIE efficiency is demonstrated. The superiority of the perchlorate counter ion is attributed to efficient stabilization of the key intermolecular π+–π interactions between neighboring luminophore molecules in the crystal lattice.Protonation of planar organic luminophores with perchloric acid turns on high solid state luminescence.A large variety of optoelectronic appliances such as photovoltaic devices,1 organic light emitting diodes,2 and organic field-effect transistors3 as well as a number of light harvesting applications including artificial photosynthesis4 and photon refining,5 rely on solid state luminophores. In 2001, Tang introduced a general method to achieve highly efficient solid state luminescence (SSL) in purely organic molecules, generally known as aggregation induced emission (AIE).6 The vast majority of AIE luminogens (AIEgens) are based on sterically hindered, bulky propeller-like molecular structures to reduce the planarity of luminophore,7 because the planar architecture is known to be detrimental to the AIE efficiency.8,7a In the meantime, the majority of luminophores with high emission intensity in solution feature a planar structure, so an approach that would allow for the design of the solid state luminogens based on the planar architecture of the known solution state emitters is highly desirable.We have recently demonstrated that the formation of intermolecular interactions between quaternary nitrogen-containing heteroaromatic cations and aromatic π-system in the solid state is a convenient and general approach to achieve AIE and to turn-on high SSL in planar organic molecules.9 The high SSL has been attributed to intermolecular charge transfer (ICT) between quaternary heteroaromatic subunits such as N-methyl pyridinium and N-methyl imidazolium cations and aromatic π-systems.9b Herein we report on a further development of the conceptual approach to achieve AIE. Specifically, we demonstrate that efficient AIE can be achieved in planar organic luminophores by simple protonation of pyridine with a suitable acid (Fig. 1). Furthermore, our study provides an important insight into the relationship between the nature of counter ion and the AIE efficiency of pyridinium salts.Open in a separate windowFig. 1Effect of counter ions on AIE and SSL.The relationship between the structure of counter ion and luminescence efficiency has been studied in several pyridinium-containing AIE luminogens.10 The highest luminescence efficiency was observed for pyridinium salts possessing a counter ion that helped to avoid the detrimental aggregation-induced quenching (ACQ) effect by minimizing intermolecular π–π interactions between planar luminophore molecules (eqn (1) and (3), Fig. 1)10a,b or by stabilizing twisted conformation of luminogens (eqn (2), Fig. 2).10c In sharp contrast, a completely opposite counter ion effect has been observed in this study. Specifically, counter ions that contributed to strengthening the intermolecular interactions between planar pyridinium luminophores have helped to achieve the highest SSL efficiency (eqn (4), Fig. 1). Perchlorate was found to be superior as the counter-ion, whereas the corresponding mesylate, nitrate as well as halides were inferior. The latter showed apparent negative correlation between the polarizability of the counter ion and SSL emission intensity (Cl > Br > I; see eqn (4), Fig. 1.). The superiority of perchlorate has been rationalized based on X-ray crystallographic analysis as demonstrated below. The striking difference of counter-ion effects in this work (eqn (4)) and in the earlier studies (eqn (1)–(3)) points to an apparent difference in mechanisms that are responsible for the AIE (Fig. 1).Open in a separate windowFig. 2Synthesis of pyridinium salts 2a,b and 4a–f. Reagents and conditions: (a) aq. HClO4, MeOH or MeCN, rt, 10 min, 83% (2a); 99% (4a); 32% (6). (b) 4 M HCl in dioxane, EtOAc, rt, 10 min, 97% (2b). (c) 4 M HCl in dioxane, 1 : 2 CH2Cl2 : hexane, rt, 10 min, 93% (4b). (d) aq. HBr, MeOH, rt, 10 min, 91% (4c). (e) aq. HI, EtOH, rt, 1 h, 61% (4d). (f) MeSO3H, MeCN, rt, 10 min, 94% (4e). (g) HNO3, MeCN, rt, 30 min, 99% (4f).Pyridinium salts 2a,b were obtained by protonation of commercially available 4-phenylpyridine 1 with aqueous HClO4 and hydrochloric acid, respectively. The protonation of previously reported 39b with HClO4, HCl, HBr, HI, MsOH and HNO3 resulted in the formation of pyridinium salts 4a–f (Fig. 2). All pyridinium salts 2a,b and 4a–f were crystalline materials.UV-vis spectra of all pyridinium salts 2a,b and 4a–f and parent heteroaromatic compounds 1 and 3 were measured in MeCN solutions at room temperature under ambient atmosphere at ca. 10−5 M concentration (see ESI, pages S11–S28†). Pyridine 1 displayed one absorption band at 251 nm (Entry Compound Additive λ abs, nm Solution λem, nm Solid λem, nm Solution, φ (%) Solid, φ (%) 1 1 — 251a — — <0.1 <0.1 2 2a — 291a 378 417 30.0 59.6 3 2b — 291a 378 434 24.6 28.5 4 3 — 238, 292, 322a 442 371, 387, 407 73.1 5.7 5 3 HClO4 (500 equiv.) — — n/a <0.1 n/a 6 3 Bu4NClO4 (500 equiv.) — 442 n/a 62.1 n/a 7 4aAb 237, 281, 377a 442c 496 n/a 5.5 8 4aBd — 237, 281, 377a 442c 503 n/a 24.1 9 4aCe 237, 281, 377a 442c 492 n/a 54.6 10 4b — 238, 288, 374a 442c 496 n/a 42.4 11 4c — 236, 282, 378a 442c 514 n/a 18.2 12 4d — 238, 292, 314, 338a 442c — n/a <0.1 13 4e — 238, 287, 376a 442c 484 n/a 45.8 14 4f — 237, 288, 377a 442c 468 n/a 33.4 15 5 — 265, 329a 416 414 2.1 2.0 16 6 — 254, 275, 388a 489 524 2.8 17.2