Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial.

AIMS: To report the longer term outcomes following either a strategy of endovascular repair first or open repair of ruptured abdominal aortic aneurysm, which are necessary for both patient and clinical decision-making. METHODS AND RESULTS: This pragmatic multicentre (29 UK and 1 Canada) trial randomized 613 patients with a clinical diagnosis of ruptured aneurysm; 316 to an endovascular first strategy (if aortic morphology is suitable, open repair if not) and 297 to open repair. The principal 1-year outcome was mortality; secondary outcomes were re-interventions, hospital discharge, health-related quality-of-life (QoL) (EQ-5D), costs, Quality-Adjusted-Life-Years (QALYs), and cost-effectiveness [incremental net benefit (INB)]. At 1 year, all-cause mortality was 41.1% for the endovascular strategy group and 45.1% for the open repair group, odds ratio 0.85 [95% confidence interval (CI) 0.62, 1.17], P = 0.325, with similar re-intervention rates in each group. The endovascular strategy group and open repair groups had average total hospital stays of 17 and 26 days, respectively, P < 0.001. Patients surviving rupture had higher average EQ-5D utility scores in the endovascular strategy vs. open repair groups, mean differences 0.087 (95% CI 0.017, 0.158), 0.068 (95% CI -0.004, 0.140) at 3 and 12 months, respectively. There were indications that QALYs were higher and costs lower for the endovascular first strategy, combining to give an INB of £3877 (95% CI £253, £7408) or €4356 (95% CI €284, €8323). CONCLUSION: An endovascular first strategy for management of ruptured aneurysms does not offer a survival benefit over 1 year but offers patients faster discharge with better QoL and is cost-effective. CLINICAL TRIAL REGISTRATION: ISRCTN 48334791

The effect of aortic morphology on peri-operative mortality of ruptured abdominal aortic aneurysm

Aims To investigate whether aneurysm shape and extent, which indicate whether a patient with ruptured abdominal aortic aneurysm (rAAA) is eligible for endovascular repair (EVAR), influence the outcome of both EVAR and open surgical repair. Methods and results The influence of six morphological parameters (maximum aortic diameter, aneurysm neck diameter, length and conicality, proximal neck angle, and maximum common iliac diameter) on mortality and reinterventions within 30 days was investigated in rAAA patients randomized before morphological assessment in the Immediate Management of the Patient with Rupture: Open Versus Endovascular strategies (IMPROVE) trial. Patients with a proven diagnosis of rAAA, who underwent repair and had their admission computerized tomography scan submitted to the core laboratory, were included. Among 458 patients (364 men, mean age 76 years), who had either EVAR (n = 177) or open repair (n = 281) started, there were 155 deaths and 88 re-interventions within 30 days of randomization analysed according to a pre-specified plan. The mean maximum aortic diameter was 8.6 cm. There were no substantial correlations between the six morphological variables. Aneurysm neck length was shorter in those undergoing open repair (vs. EVAR). Aneurysm neck length (mean 23.3, SD 16.1 mm) was inversely associated with mortality for open repair and overall: adjusted OR 0.72 (95% CI 0.57, 0.92) for each 16 mm (SD) increase in length. There were no convincing associations of morphological parameters with reinterventions. Conclusion Short aneurysm necks adversely influence mortality after open repair of rAAA and preclude conventional EVAR. This may help explain why observational studies, but not randomized trials, have shown an early survival benefit for EVAR. Clinical trial registration: ISRCTN 48334791

Crime in ljubljana in the time of covid-19 pandemic

V magistrskem delu je obravnavana kriminaliteta v Ljubljani v času pandemije koronavirusa covid-19, ki se je začela konec leta 2019. Prizadela je skoraj vse države in ozemlja sveta. Ker se je koronavirus covid-19 nenadzorovano širil, so številne vlade sprejele ukrepe za zajezitev širjenja okužb. Eden najbolj ključnih ukrepov, ki je vplival na spremembe gibanja kriminalitete, je bil omejevanje gibanja ljudi. Ljudi je prisilil, da so ostali doma. Prvi del magistrskega je teoretičen. V njem so predstavljeni ukrepi, ki jih je Slovenija sprejela za zajezitev koronavirusa covid-19, gibanje kriminalitete v času pandemije, kriminaliteta v Sloveniji med prvim in drugim valom pandemije covid-19, kako so izkoristili covid-19 za izvajanje kriminalitete, vzroki za porast oziroma upad kriminalitete in pa predvidevanja o kriminaliteti po pandemiji. Drug del magistrskega dela pa zajema empirični del, ki temelji na raziskavi kriminalitete v mestu Ljubljana v času pandemije koronavirusa covid-19. Na podlagi podatkov, ki smo jih dobili od drugih avtorjev, smo lahko analizirali najpogostejša premoženjska in nasilna kazniva dejanja za obdobje od 1. 1. do 31. 8. 2020 in jih primerjali z letom 2019. Zaznali smo upad vlomov, tatvin, ropov, hudih telesnih poškodb, posilstev, nasilja v družini. V porastu pa so bili umori, tatvine motornih vozil in roparske tatvine.The master\u27s thesis deals with crime in Ljubljana during the Covid-19 coronavirus pandemic, which began at the end of 2019. It affected almost all countries and territories in the world. As the Covid-19 coronavirus was spreading uncontrollably, many governments have taken steps to curb the spread of infections. One of the most key measures that has influenced changes in the criminality movement has been to restrict the movement of people. It forced people to stay home. The first part of the master\u27s thesis is theoretical. It presents the measures taken by Slovenia to curb the Covid-19 coronavirus, the movement of criminality during the pandemic, criminality in Slovenia during the first and second waves of the Covid-19 pandemic, how they took advantage of Covid-19 to commit criminality, the reasons for the increase or decline of criminality and predictions of criminality after the pandemic. The second part of the master\u27s thesis includes an empirical part based on a criminality research in the city of Ljubljana during the Covid-19 coronavirus pandemic. Based on data obtained from other authors, we were able to analyse the most common property and violent criminal acts for the period from the 1st January to the 31st August 2020 and compare them with year 2019. We detected a decline in burglaries, thefts, robberies, grievous bodily harm, rape, domestic violence. However, murders, thefts of motor vehicles and robbery thefts were on the rise

Surrogacy

Napredek v tehnološkem razvoju je pripomogel tudi k razvoju novih, sodobnih reproduktivnih tehnik in s tem omogočil uporabo nadomestnega materinstva. Nadomestno materinstvo je ena izmed možnosti, za katero se odločijo tako heteroseksualni, kot homoseksualni pari, ki si želijo ustvariti življenje z otroki. Nadomestno materinstvo je praviloma posledica postopka oploditve z biomedicinsko pomočjo,kjer pride do nosečnosti nadomestne matere na ne tradicionalen način, torej na drugačen način kot s spolnim odnosom. Ženska oziroma nadomestna mati v večini primerov za denar ali za neko korist zanosi in rodi otroka v dogovoru s tretjo osebo, ki potem tega otroka posvoji. Večina teh nadomestnih mater je iz nižjega kastnega sistema, kjer jih družine prisilijo v tovrstno dejanje, da se lahko preživijo. Maternice teh žensk so uporabljene kot tovarne za najem. In s tem se kaže izkoriščanje žensk v socialnih stiskah za nadomestno materinstvo, otroka pa ponižuje na raven stvari, s katero je dopustno trgovati. Trgovanje z otroki je kvalificirana oblika trgovanja z ljudmi, s katerim se ukvarjajo številne kriminalne združbe, katerim je cilj dodaten zaslužek. Z denarjem lahko kupiš marsikaj, pri nadomestnem materinstvu pa se z odkupom otroka, otrok odtuji od prsi matere in tu se postavlja vprašanje, ali ima človeško življenje ceno in ali je tako dejanje etično in moralno sprejemljivo, saj, ni v skladu s človekovimi pravicami in dostojanstvom žensk. Po svetu je na tisoče sirot, ki nimajo družine, zato ne bi smelo biti nobene potrebe po takih potencialno suženjskih oblikah poti do otroka, samo zato, da starši dobijo v roke svoj genski material. Kdor iskreno čuti notranjo potrebo po tem, da bi skrbel za otroka in ga imel rad, jo lahko odlično in v celoti poteši tudi s tujim otrokom.The rapid development of new technologies, especially the speed and capacity of gene technology, has greatly influenced the development of medicine in recent decades. New techniques nowadays present a range of dilemmas, both ethical and legal. Among these techniques, surrogacy is currently the most exposed, as it has recently become a much sought alternative for couples who cannot have biological children. So surrogacy has allowed reproduction not only for heterosexual but also for homosexual couples (Lahl, 2017). The market of surrogacy has begun to develop around the traditional surrogacy In this case, the female surrogate mothers are fertilized by the intended sperm cell of the father and, with the help of their own eggs, they bear and give birth to the baby. Later, however, the market of gestational surrogacy began to develop, in which surrogacyoccurs through a fertilization procedure with biomedical help. In this procedure, the eggs and sperm are joined in vitro, which means in the laboratory, outside the human body, and then the embryo is inserted into the uterus of the surrogate mother. Gestational surrogacy happens in an artificial way, whereas the traditional surrogacy happens naturally - through sexual intercourse (Goodwin, 2010). The surrogate mother is a woman who, in the commercial form of surrogacy, receives payment to give up parental rights and the child she has born and given birth to, and hands it over to the intended parents. In some countries this is legal. The surrogate mothers are paid for their time and suffering by the surrogate agencies, just as workers are paid in the factories. The only difference is that in this case their wombs are the factories. Most of these surrogate mothers belong to the lower caste system, where families force them into this act so that they can survive. And this shows the exploitation of women in social distress for surrogate motherhood, and degrades the child to the level of things that can be trafficked (Overall, 2015)

The effect of three polyphenols and some other anti-oxidant substances on amyloid fibril formation by human cystatin C

Human cystatin C (CysC) is an amyloid forming protein involved in the hereditary cerebral amyloid angiopathy (HCCAA) that affects arteries in the brain and the peripheral nervous system. In this study we measured the influence of several substances on human CysC aggregation and amyloid fibril formation, induced at pH 4 in vitro. The effect of three polyphenols: resveratrol, quercetin and curcumin and of two antioxidants: vitamin C (VitC) and N-acetyl-L-cysteine (NAC) was explored as well as the effect of sulphoraphane (SF) and α-lipoic acid (AL). The formation of amyloid fibrils was followed by Thioflavin T (ThT) fluorescence and by transmission electron microscopy (TEM). Effects on the length of the lag phase were revealed by following the increase of ThT fluorescence intensity with time. The amount and morphology of fibrils in comparison to prefibrillar aggregates and globular oligomers were evaluated by TEM at the plateau stage of the reaction. Thermal stabilization of the CysC monomer by the small compounds was measured by differential scanning fluorimetry (DSF). NAC, VitC and SF exhibited the largest inhibitory effect on amyloid fibril growth. The effects of polyphenols were not significant, apart from resveratrol, which partly inhibited the amyloid fibril growth

Modelling impacts of a municipal spatial plan of land-use changes on surface water quality—example from Goriška Brda in Slovenia

Intensive agriculture causes nutrient leaching and accelerates erosion processes, which threatens the good quality status of surface waters, as proposed by the European Union (EU) Water Framework Directive. The purpose of this study was to define the impact of two alternative agricultural land-use change scenarios defined in a Municipal Spatial Plan on surface water quality by using the Agricultural Policy/Environmental eXtender (APEX) model. As experimental area, we chose a small Kožbanjšček stream catchment (1464 ha) situated in the Goriška Brda region in Slovenia. The area, due to favorable conditions for vineyards, is facing increasing deforestation. The change of 66.3 ha of forests to vineyards would increase the sediment, nitrate, and phosphorus loads in the stream by 24.8%, 17.1%, and 10.7%, respectively. With the implementation of vegetative buffer strips as a mitigation measure of the current situation, we could reduce the sediment, nitrate, and phosphorus loads by 17.9%, 11.1%, and 3.1%, respectively, while a combination of the two land-use change scenarios would result in a slight increase of the above-mentioned loads, corresponding to 0.61%, 2.1%, and 6.6%, respectively, compared to the baseline situation. The results confirm that, as we can increase pollution levels with deforestation, we can also reduce water pollution by choosing proper types of land management measures

Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus

Autolysin E (AtlE) is a cell wall degrading enzyme that catalyzes the hydrolysis of the β-1,4-glycosidic bond between the N-acetylglucosamine and N-acetylmuramic acid units of the bacterial peptidoglycan. Using our recently determined crystal structure of AtlE from Staphylococcus aureus and a combination of pharmacophore modeling, similarity search, and molecular docking, a series of (Phenylureido)piperidinyl benzamides were identified as potential binders and surface plasmon resonance (SPR) and saturation-transfer difference (STD) NMR experiments revealed that discovered compounds bind to AtlE in a lower micromolar range. (phenylureido)piperidinyl benzamides are the first reported non-substrate-like compounds that interact with this enzyme and enable further study of the interaction of small molecules with bacterial AtlE as potential inhibitors of this target

A Water-Assisted Catalytic Mechanism in Glycoside Hydrolases Demonstrated on the Staphylococcus aureus Autolysin E

Autolysin E (AtlE), from Staphylococcus aureus, is a cell-wall-degrading enzyme that is a potential drug target. It is a member of the glycoside hydrolase (GH) class, enzymes that commonly have either two catalytic residues and hydrolyze their substrates by inverting or retaining mechanisms or one catalytic residue and undergo retaining, substrate-assisted catalysis. Here, we address the catalytic mechanism of AtlE. Site-directed mutagenesis studies identified Glu138 as the only catalytic residue. Quantum mechanics/molecular mechanics (QM/MM) simulations of the possible reaction pathways suggest that hydrolysis proceeds via a retaining, water-assisted mechanism and an oxocarbenium ion like transition state. These results, on the basis of data from a member of the hydrolase GH73 family, support the hypothesis of the presence of an alternative catalytic mechanism in glycoside hydrolases, which can be considered in the design of future AtlE inhibitors

A Water-Assisted Catalytic Mechanism in Glycoside Hydrolases Demonstrated on the Staphylococcus aureus Autolysin E

Autolysin E (AtlE), from Staphylococcus aureus, is a cell-wall-degrading enzyme that is a potential drug target. It is a member of the glycoside hydrolase (GH) class, enzymes that commonly have either two catalytic residues and hydrolyze their substrates by inverting or retaining mechanisms or one catalytic residue and undergo retaining, substrate-assisted catalysis. Here, we address the catalytic mechanism of AtlE. Site-directed mutagenesis studies identified Glu138 as the only catalytic residue. Quantum mechanics/molecular mechanics (QM/MM) simulations of the possible reaction pathways suggest that hydrolysis proceeds via a retaining, water-assisted mechanism and an oxocarbenium ion like transition state. These results, on the basis of data from a member of the hydrolase GH73 family, support the hypothesis of the presence of an alternative catalytic mechanism in glycoside hydrolases, which can be considered in the design of future AtlE inhibitors

A Water-Assisted Catalytic Mechanism in Glycoside Hydrolases Demonstrated on the Staphylococcus aureus Autolysin E

Autolysin E (AtlE), from Staphylococcus aureus, is a cell-wall-degrading enzyme that is a potential drug target. It is a member of the glycoside hydrolase (GH) class, enzymes that commonly have either two catalytic residues and hydrolyze their substrates by inverting or retaining mechanisms or one catalytic residue and undergo retaining, substrate-assisted catalysis. Here, we address the catalytic mechanism of AtlE. Site-directed mutagenesis studies identified Glu138 as the only catalytic residue. Quantum mechanics/molecular mechanics (QM/MM) simulations of the possible reaction pathways suggest that hydrolysis proceeds via a retaining, water-assisted mechanism and an oxocarbenium ion like transition state. These results, on the basis of data from a member of the hydrolase GH73 family, support the hypothesis of the presence of an alternative catalytic mechanism in glycoside hydrolases, which can be considered in the design of future AtlE inhibitors