Methods for Mesh Implantation Efficacy Assessment in Rectocele

Aim. A methodological review on mesh implantation efficacy assessment in surgery for rectocele.Key points. Specialised quiz surveys are among the most appropriate methods to assess surgical intervention efficacy. The questionnaires that enable pre- and postsurgery rectocele grading include PFDI-20 (Pelvic Floor Distress Inventory), the colonic evacuation disorder scale and Cleveland Constipation Scoring System. These surveys determine the surgical intervention efficacy dynamically in conjunction with instrumental surgery assessment techniques.Conclusion. Clinical practice at the Ryzhikh National Medical Research Centre for Coloproctology combines the originally developed colonic evacuation disorder scale (2003) and PFDI-20. The combined scales allow for a comprehensive symptom assessment in patients with rectocele and other descending perineum syndrome manifestations prior to surgery, as well as symptom dynamics evaluation postoperatively, which, in link with defecography, enables a complete appraisal of the surgical effect

Investigation of the Deformation Activation Volume of an Ultrafinegrained Ti50Ni50 Alloy

© 2015 Springer Science+Business Media New York The mechanical properties, strain rate sensitivity (m) and deformation activation volume (ΔV) are investigated at the experimental temperatures from 20 to 400°С in a Ti50Ni50alloy in a coarse-grained (CG) state with the austenite grain size D = 200 μm and in an ultrafine-grained (UFG) state with D = 700 μm following an ECAP treatment. It is observed that this treatment improves the yield strength of the alloy compared to its CG-state. The strain rate sensitivity, m, is found to be by a factor of 1.5–2 higher than that of CG-specimens; it increases with the temperature in both states of the material. As the temperature of the material in tension increases up to Т = 150–250°С, parameter ΔV increases to its maximum and with a further growth of the experimental temperature to 400°С, parameter ΔV decreases. The deformation activation volume of the alloy in the UFG-state is by a factor of 2–4 larger than that in the CG-state for the same experimental temperatures

EXCESSIVE MORTALITY IN WINTER IN MOSCOW AND ITS ECONOMIC VALUE DURING THE YEARS 2007-2014

Aim. To study the excessive mortality during the winter (EMW) from all causes and CVD, monthly values of mortality; to evaluate social and economic harm due to EMW in Moscow.Material and methods. The calculation of EMW (%) was done for Moscow by the mortality from all causes and from CVD by a special equation. For monthly values of mortality we estimated the average range per month by absolute number of the deaths — absolute parameters of mortality by every analyzed year were ranged from 1 to 12, and mean value of the range was calculated.Results. Mean EMW per 8 years was 5,1%, for CVD higher — 8,8%. In Moscow there is an influence of the anomaly heat of 2010 — EMW was 4,5% from all causes, from CVD — 6,0%. Maximum number of deaths was registered in January and march. Gross EH by 2007-2013 from EMW was 7,9 billion rubles in Moscow.Conclusion. A significant part of EMW are the deaths from CVD. The amount of EH from EMW has confirmed the shown previously relation from two factors — number of deaths and size of GRP in region. For Moscow — the capital of Russia, having the highest values of economic development, the harm, that is quite significant, grounds the necessity of investments into excessive mortality and search for effective by decrease of mortality in winter time

Experimental Tests of Neutron Shielding for the ATLAS Forward Region

Experimental tests devoted to the optimization of the neutron shielding for the ATLAS forward region were performed at the CERN-PS with a 4 GeV/c proton beam. Spectra of fast neutrons, slow neutrons and gamma rays escaping a block of iron (40$\times$40$\times$80 cm$^3$) shielded with different types of neutron and gamma shields (pure polyethylene - PE, borated polyethylene - BPE, lithium filled polyethylene - LiPE, lead, iron) were measured by means of plastic scintillators, a Bonner spectrometer, a HPGe detector and a slow neutron detector. Effectiveness of different types of shielding agaisnt neutrons and $\gamma$-rays were compared. The idea of a segmented outer layer shielding (iron, BPE, iron, LiPE) for the ATLAS Forward Region was also tested

Merkel cell polyomavirus small t antigen induces cancer and embryonic merkel cell proliferation in a transgenic mouse model

Merkel cell polyomavirus (MCV) causes the majority of human Merkel cell carcinomas (MCC) and encodes a small T (sT) antigen that transforms immortalized rodent fibroblasts in vitro. To develop a mouse model for MCV sT-induced carcinogenesis, we generated transgenic mice with a flox-stop-flox MCV sT sequence homologously recombined at the ROSA locus (ROSAsT), allowing Cre-mediated, conditional MCV sT expression. Standard tamoxifen (TMX) administration to adult UbcCreERT2; ROSAsT mice, in which Cre is ubiquitously expressed, resulted in MCV sT expression in multiple organs that was uniformly lethal within 5 days. Conversely, most adult UbcCreERT2; ROSAsT mice survived low-dose tamoxifen administration but developed ear lobe dermal hyperkeratosis and hypergranulosis. Simultaneous MCV sT expression and conditional homozygous p53 deletion generated multi-focal, poorly-differentiated, highly anaplastic tumors in the spleens and livers of mice after 60 days of TMX treatment. Mouse embryonic fibroblasts from these mice induced to express MCV sT exhibited anchorage-independent cell growth. To examine Merkel cell pathology, MCV sT expression was also induced during mid-embryogenesis in Merkel cells of Atoh1CreERT2/+; ROSAsT mice, which lead to significantly increased Merkel cell numbers in touch domes at late embryonic ages that normalized postnatally. Tamoxifen administration to adult Atoh1CreERT2/+; ROSAsT: Atoh1CreERT2/+; ROSAsT; p53flox/flox mice had no effects on Merkel cell numbers and did not induce tumor formation. Taken together, these results show that MCV sT stimulates progenitor Merkel cell proliferation in embryonic mice and is a bona fide viral oncoprotein that induces full cancer cell transformation in the p53-null setting

The LHCb upgrade I

The LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software

Ефективний синтез інгібіторів PARP на основі 4-трифторометилзаміщеного скафолду 3,6,7,7a-тетрагідро-1H-піроло[3,4-d]піримідин-2,5-діону

Poly(ADP-ribose) polymerases (PARPs) are key enzymes in the DNA repair pathway. Inhibitors of these enzymes belong to a new type of anticancer drugs that selectively kill cancer cells by targeting the homologous recombination genetic defects. This study presents a new synthetic approach to PARP inhibitors containing a 4-trifluoromethyl substituted 3,6,7,7a-tetrahydro-1H-pyrrolo[3,4-d]pyrimidine-2,5-dione scaffold. The method is based on a practical one-step cyclocondensation of 2-(2-oxo-1,2,3,4-tetrahydropyrimidin-4-yl)acetic acid derivatives via the Curtius rearrangement of the corresponding acyl azides formed in situ upon the treatment with diphenylphosphoryl azide. The resulting products have been found to possess a potent inhibitory effect on PARP-1 and PARP-2 isoforms of poly(ADP-ribose) polymerases. The structure–activity analysis has revealed that the N1-aryl substituent is crucial to the selectivity and high potency towards PARP-2, and that the p-fluorobenzyl group is the optimal group for the non-selective and potent PARP-1 and PARP-2 inhibition.Полі(АДФ-рибоза)-полімерази (PARP) є ключовими ензимами в процесах репарації ДНК. Інгібітори цих ензимів належать до нового типу протипухлинних препаратів, які вибірково вражають ракові клітини, націлюючись на генетичні дефекти гомологічної рекомбінації. У роботі наведено новий синтетичний підхід до інгібіторів PARP, що містять 4-трифторометилзаміщений скафолд 3,6,7,7a-тетрагідро-1H-піроло[3,4-d]піримідин-2,5-діону. Метод базується на практичній одностадійній циклоконденсації похідних 2-(2-оксо-1,2,3,4-тетрагідропіримідин-4-іл)оцтової кислоти за допомогою перегрупування Курціуса відповідних ацилазидів, утворених in situ за обробки кислот дифенілфосфорилазидом. Визначено, що одержані продукти виявляють значний інгібувальний ефект на ізоформи PARP-1 і PARP-2 полі(АДФ-рибоза)-полімераз. Аналізом взаємозв’язку між структурою та активністю доведено, що N1-арильний замісник має суттєве значення для селективності та високої активності до PARP-2, а пара-фторобензильна група є оптимальною для вираженого невибіркового інгібування PARP-1 та PARP-2

NEW ORAL ANTICOAGULANTS: IS THAT PLAUSIBLE TO IMPLEMENT THE DATA FROM INTERNATIONAL TRIALS TO RUSSIAN POPULATION?

Aim. To compare, in what extent are the patients with atrial fibrillation (AF), included into three large randomized clinical trials (RCT) of the new oral anticoagulants (NOAC), comparable with Russian patients with AF. Material and methods. We revealed the results of the published Russian registries showing clinical and anamnestic data on the patients with all types of AF. The research done with the contents of journals and the list of Russian epidemiological studies in cardiology. Totally 6 papers selected that match with the requirements of contemporary registry. Results. Patients included into RCT, differ by the severity of the disease. In RELY-AF and ARISTOTLE study patients were quite similar, however ROCKET-AF was significantly different by the severity of included patients diseases. Of 6 selected Russian registries, two were outpatients (RECVAZA-Ryazan and RECVAZA-Yaroslavl), two registries of specialized units (PROFIL and the registry based on the FMSVU), and acute myocardial infarction (LIS-1) and stroke (LIS-2) registries. These patients are the most similar with those included into ROCJET-AF. However, by the range of parameters that characterize the severity of pathology, they even worse comparing to those with ROCKET-AF. The patients included into FSMSU registry and PROFIL are more relevant to those included into RELY-AF and ARISTOTLE.Conclusion. Currently there are no large registries of AF in Russian Federation. In general, the Russian "portrait" of AF-patient has worse course of the disease, which those included to RCT: ROCKET-AF, RELY- AF and ARISTOTLE, that makes it very important to implement the data obtained in these three large-scale RCT in Russian population with care