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PURPOSE. To determine whether in vivo confocal microscopy (IVCM) of the cornea can be used for the label-free detection and monitoring of lymph vessels in live corneas. METHODS. Parallel corneal hemangiogenesis and lymphangiogenesis was induced by the placement of a single suture in one cornea of male Wistar rats. Fourteen days after suture placement and under general anesthesia, laser-scanning IVCM was performed in the vascularized region. Corneas were subsequently excised for flat-mount double immunofluorescence with a pan-endothelial marker (PECAM-1/CD31) and a lymphatic endothelial specific marker (LYVE-1). Using the suture area and prominent blood vessels as points of reference, the identical microscopic region was located in both fluorescent and archived in vivo images. Additionally, vessel diameter, lumen contrast, and cell diameter and velocity within vessels were quantified from in vivo images. RESULTS. Comparison of identical corneal regions in fluorescence and in vivo revealed prominent CD31(+)/LYVE-1(3+) lymph vessels that were visible in vivo. In vivo, corneal lymph vessels were located in the vascularized area in the same focal plane as blood vessels but had a darker lumen (P andlt; 0.001) sparsely populated by highly reflective cells with diameters similar to those of leukocytes in blood vessels (P = 0.61). Cell velocity in lymph vessels was significantly reduced compared with blood particle velocity (P andlt; 0.001). Morphologic characteristics enabled subsequent identification of corneal lymphatics in live, vascularized rat corneas before immunofluorescence labeling. CONCLUSIONS. IVCM enabled the nondestructive, label-free, in vivo detection of corneal lymphatics. IVCM provides the possibility of observing lymphatic activity in the same live corneas longitudinally and, as a clinical instrument, of monitoring corneal lymphatics in live human subjects

Criminal Law: Demise of “Status”—“Act” Distinction in Symptomatic Crimes of Narcotic Addiction

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Tendencies of globalization of development of international tourism

Проаналізовано сучасні тенденції розвитку міжнародного туризму як провідного сегмента світового ринку, однієї із найважливіших складових процесу глобалізації. Визначено передумови глобалізації світового туристичного ринку, окреслено перспективи розвитку системи міжнародного туризму в сучасних умовах. Зміст міжнародного туризму як економічної категорії представлено як функціональну спрямованість його впливу на формування сучасної глобальної економічної системи, що проявляється в єдності його функцій.In the article modern progress of international tourism trends are analysed as a leading world market segment, one of major constituents of process of globalization. Pre-conditions of globalization of world tourist market are certain, the prospects of development of the system of international tourism are outlined in modern terms. The table of contents of international tourism as an economic category is presented as a functional orientation of his influence on forming of the modern global economic system that shows up in unity of his functions. Passing of international tourism to the global stage of the development was caused by the specific of the market state of affairs of the concrete historical stage, aspiring of large tourist companies to minimization of prime price of tourist package and increase of guarantees of grant of the announced tourist services of the proper quality; and also by the height of investment attractiveness of tourist business as a result of mass character of international tourism and increase of effect of scale in him. Global international tourism certainly as the socio-economic phenomenon that depends already not on domestic, but from external factors, maintenance and quantity of that determined by a global world concord the members of that are related to each other in all spheres of public life, including an economy, policy, ideology, culture, social sphere, ecology, safety. By the basic components of globalization of international tourism following: expansion of international economic connections in a tourist production, increase of internationalization of factors of tourist production, distribution of multinationals corporations in tourist business

Structural and property features of polymer compositions based on polyamide 6 and polyolefin functionalized mixtures

Изучена возможность получения полимер-полимерных композиций полиамида 6 (ПА6) с функционализированной смесью полибутена (ПБ) и сополимера этилена с октеном (СЭО), а также проанализированы особенности структуры и свойств полученных материалов. Показано, что функционализированные смеси ПБ/СЭО (ф(ПБ/СЭО)) по своим модифицирующим свойствам превосходят исходные и функционализированные ПБ и СЭО. При использовании в качестве модификаторов ф(ПБ/СЭО) микроструктура и степень гетерогенности в ПА6 композициях достигают такого уровня, при котором возможно получать смесевые полимер-полимерные композиции с улучшенным комплексом свойств: с повышенной ударной вязкостью, которая достигает 45–60 кДж/м 2 , и деформационно-прочностными характеристиками, близкими к исходному ПА6. Полученные результаты следует учитывать при разработке реальных материалов технического назначения с улучшенными свойствами на базе ПА6 и функционализированных полиолефинов.The possibility of obtaining polyamide 6 (PA6) polymer-polymer compositions with a functionalized mixture of polybutene (PB) and octene ethylene copolymer (OEC) has been studied. Structural and property features of the obtained materials have been analyzed. It has been shown that concerning the modifying properties functionalized PB/OEC mixtures (f(PB/OEC)) are superior to the initial and functionalized PB and OEC. When using f(PB/OEC) as modifiers, the microstructure and heterogeneity degree in PA6 compo- sitions reach a level at which it is possible to obtain mixed polymer-polymer compositions with an improved set of properties such as increased impact strength that reaches 45–60 kJ/m 2 , and deformation-strength characteristics close to the initial PA6. The results should be taken into account when developing real technical materials with improved properties based on PA6 and functionalized polyolefins

Phosphorylcholine and KR12-Containing Corneal Implants in HSV-1-Infected Rabbit Corneas

Severe HSV-1 infection can cause blindness due to tissue damage from severe inflammation. Due to the high risk of graft failure in HSV-1-infected individuals, cornea transplantation to restore vision is often contraindicated. We tested the capacity for cell-free biosynthetic implants made from recombinant human collagen type III and 2-methacryloyloxyethyl phosphorylcholine (RHCIII-MPC) to suppress inflammation and promote tissue regeneration in the damaged corneas. To block viral reactivation, we incorporated silica dioxide nanoparticles releasing KR12, the small bioactive core fragment of LL37, an innate cationic host defense peptide produced by corneal cells. KR12 is more reactive and smaller than LL37, so more KR12 molecules can be incorporated into nanoparticles for delivery. Unlike LL37, which was cytotoxic, KR12 was cell-friendly and showed little cytotoxicity at doses that blocked HSV-1 activity in vitro, instead enabling rapid wound closure in cultures of human epithelial cells. Composite implants released KR12 for up to 3 weeks in vitro. The implant was also tested in vivo on HSV-1-infected rabbit corneas where it was grafted by anterior lamellar keratoplasty. Adding KR12 to RHCIII-MPC did not reduce HSV-1 viral loads or the inflammation resulting in neovascularization. Nevertheless, the composite implants reduced viral spread sufficiently to allow stable corneal epithelium, stroma, and nerve regeneration over a 6-month observation period

Biomaterials-enabled cornea regeneration in patients at high risk for rejection of donor tissue transplantation

The severe worldwide shortage of donor organs, and severe pathologies placing patients at high risk for rejecting conventional cornea transplantation, have left many corneal blind patients untreated. Following successful pre-clinical evaluation in mini-pigs, we tested a biomaterials-enabled pro-regeneration strategy to restore corneal integrity in an open-label observational study of six patients. Cell-free corneal implants comprising recombinant human collagen and phosphorylcholine were grafted by anterior lamellar keratoplasty into corneas of unilaterally blind patients diagnosed at high-risk for rejecting donor allografts. They were followed-up for a mean of 24 months. Patients with acute disease (ulceration) were relieved of pain and discomfort within 1-2 weeks post-operation. Patients with scarred or ulcerated corneas from severe infection showed better vision improvement, followed by corneas with burns. Corneas with immune or degenerative conditions transplanted for symptom relief only showed no vision improvement overall. However, grafting promoted nerve regeneration as observed by improved touch sensitivity to normal levels in all patients tested, even for those with little/no sensitivity before treatment. Overall, three out of six patients showed significant vision improvement. Others were sufficiently stabilized to allow follow-on surgery to restore vision. Grafting outcomes in mini-pig corneas were superior to those in human subjects, emphasizing that animal models are only predictive for patients with non-severely pathological corneas; however, for establishing parameters such as stable corneal regeneration and nerve regeneration, our pig model is satisfactory. While further testing is merited, we have nevertheless shown that cell-free implants are potentially safe, efficacious options for treating high-risk patients

Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy

We formed the GEnetics of Nephropathy–an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 × 10−9). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated