Репозиторий Университета

© 2018 The Author(s). Background: Although the number of antihyperglycemic agents has expanded significantly, sulfonylureas (in particular gliclazide) remain an important option because of a variety of patient and health system factors. The large, real world, observational, and international EASYDia trial evaluated the effectiveness of gliclazide modified release (MR) 60 mg in individuals with type 2 diabetes with a broad range of diabetes history, body mass index (BMI) and background antihyperglycemic treatment. Methods: A total of 7170 participants from eight countries, age ≥ 35 years with HbA1c ≥ 7.5% and not treated with insulin, were prescribed 30-120 mg of gliclazide MR 60 mg once daily. HbA1c goals were individualized and dosing uptitrated, as required, over the 6-month long study. In this post hoc subanalysis, efficacy endpoints were analyzed according to stratified baseline HbA1c levels, weight and glucose-lowering regimens. Episodes of hypoglycemia requiring assistance were documented. Results: At baseline, mean age was 58.9 years, HbA1c 8.8%, BMI 30.1 kg/m2, and diabetes duration 5.1 years. At study end, clinically significant HbA1c improvements (mean change - 1.78%) were noted across all baseline HbA1c strata (> 7.0 to ≤ 8.0%, > 8.0 to ≤ 9.0%, > 9.0 to ≤ 10.0%, and > 10.0%), BMI classifications (18.5 to < 25.0, 25.0 to < 30.0, and ≥ 30.0 kg/m2), and regardless of the original diabetes treatment regimen (P < 0.001 in all cases). In contrast to the subgroups with BMI 25.0-30.0 and ≥ 30.0 kg/m2 that registered weight losses of 0.9 and 2.2 kg, respectively (P < 0.001 vs. baseline weight); the BMI 18.5-24.9 kg/m2 subgroup gained a mean 0.5 kg (P < 0.02 vs. baseline weight). Severe hypoglycemic events were rare (0.06%). Conclusions: Progressive gliclazide MR 60 mg uptitration was well tolerated and lowered HbA1c across a broad range of HbA1c, BMI and background glucose-lowering therapy. Weight loss was noted when BMI was ≥ 25.0 kg/m2. Individuals with the highest baseline HbA1c and BMI experienced the greatest HbA1c and weight improvements. Trial registration ISRCTN Registry ISRCTN00943368 on 1st July 2011

BACKGROUND: total hip replacement has long ago become the «golden standard» for the treatment of dysplastic coxarthrosis in thousands of the patients receiving it every year. In the meantime, the analysis of the specialized literature gives evidence of the lack of a systematic and personified approach to the rehabilitation treatment. AIM: The objective of the present study was to improve medical rehabilitation of the patients following the total hip replacement and to develop the personalized programs for walking modality reconstruction taking into consideration the age and the body weight of the patients. PATIENTS AND METHODS: A total of 240 patients were available for the observation including 184 women and 56 men. They were divided into three study groups and one control group, with the differentiation into the following three subgroups: one comprised of the patients of moderate acerage age and body weight, the other containing the obese patients (BMI>35), and the third one involving the elderly patients (age >70 years); each subgroup consisted of 20 patients. All the patients received the early basic rehabilitation treatment, those in the study groups had to perform in addition the robotic training based on the use of hardware techniques supplemented by passive mechanotherapy and electromyostimulation designed to restore the walking stereotype with three types of devices: body weight unloading, video-reconstruction associated with biological feedback and robototherapy. RESULTS: The comparative analysis of the effectiveness of various methods of gait reconstruction has demonstrated the high effectiveness of the application of the hardware technique in the patients of moderate acerage age and body weight. At the same time, the elderly patients had a significantly higher rate of successful walking reconstruction efficiency under the influence of the video-associated training with biological feedback (3 times that achieved with training using the device for unloading the body weight and 4 times compared with the result of a course of robotic walk. The evaluation of the application of the techniques for the gait stereotype reconstruction in the obese patients gave evidence of the advantage of the Lokomat robotic trainings that produced 6 times better results than unloading of the body weight and 5 times better ones than the video-associated training with biological feedback. DISCUSSION: The results of the present study are on the whole comparable with the data reported by other authors although its design was different from that of the majority of the published studies in that our patients were allocated to different subgroups for the further personalization of the methods applied to restore the gait stereotype. The factors limiting the use of the results of this study include the medium-high level of the patients' welfare most of whom are residents of the city of Moscow and Moscow region characterized by a relatively high quality and accessibility of health care. It means that the results of such studies as the one described in the present article are directly related to the quality and accessibility of health care and can be extrapolated only to the socially safe and well-to-do patients. CONCLUSIONS: All the hardware techniques are equally effective in the patients of moderate average age and body weight. The elderly patients showed the best results using the video-reconstruction associated with biological feedback, while the Locomat technique was especially useful for the obese patients.

© 2018, Copyright © Kazan (Volga region) Federal University. The syntheses of a series of novel derivatives of stilbazole and their azo-analogs bearing the phenylalkenyl and phenyldiazenyl substituents at position 6 of the pyridoxine ring are reported. The observed cis/trans regioselectivity in the Wittig reaction between triphenylbenzylphosphonium chloride and carbonyl derivatives of pyridoxine ketal is discussed with respect to transition state intermediates, nature of base used in the reaction, and resonance transformations in the pyridoxine system. The azo-derivatives are obtained by azocoupling of the diazonium salts of sulfanilic or 4-aminophenyl-1,3-disulfonic acids with the corresponding pyridoxine acetals. Nine compounds from the obtained experimental series are capable of emitting second harmonic generation light, although with a reduced efficiency as compared to well known KH2PO4 or LiIO3 perovskite crystals, but with excellent beam resistance under laser irradiation, which makes them potential starting points for the development of novel nonlinear optical materials.

© 2018 Taylor  &  Francis Group, LLC. The mechanism of the molecular circadian clocks is currently understood as a transcription/translation feedback loop involving more than ten genes. Genetic variation at some of loci in these genes has been shaped by adaptation to environmental factors. In particular, latitudinal clines in allele frequency were documented in several animal species, but the contradictory conclusions were drawn from the results of rare human studies. Here we tested whether the out-of-African dispersal of human populations to higher latitudes of the Eurasian continent was associated with latitude-dependent shifts in allele frequency at polymorphic loci in genes of three (reference, circadian and skin pigmentation) groups. In order to detect the genetics-based signatures left by latitude-driven adaptation and to distinguish them from the confounding effects of population demographic history, we analyzed allele frequencies in 1594 individuals from 5 African and 11 Eurasian populations of the 1000 Genomes Project Phase 3. Up to 80 polymorphisms with global minor allele frequency > 0.2 were sampled from each of 36 genes (1665 polymorphisms in total). As expected, percentage of polymorphisms demonstrating both significantly enlarged differentiation of Eurasian populations on allele frequency and significant correlation between latitude and allele frequency was significantly higher in pigmentation genes compared to circadian genes and in circadian genes compared to reference genes. We also showed that the latitude-driven adaptation can be separated from genetic consequences of demographic perturbations by comparison of results obtained for the whole set of 16 African and Eurasian populations with results for only Eurasian populations that share the common demographic history. The revealed latitudinal clines in allele frequency seemed to be shaped by polygenic selection occurring by small allele frequency shifts spread across many loci in circadian and non-circadian genes. The present results provided a rationale for necessity to facilitate candidate gene studies by prioritizing genetic markers of chronotype.

© 2017 Taylor  &  Francis. In this study, we tested a hypothesis that a short-term estradiol therapy may reduce blood pressure in preeclampsia by modulating plasma oxidative stress. The intramuscular injections of 10 mg 17-beta-estradiol were prescribed to preeclamptic pregnant women during the 3-day therapy before a labor induction. The analyses of mean arterial pressure (MAP), serum estradiol concentrations, plasma superoxide anion (O2.), hydrogen peroxide (H2O2), nitrites (NO2−), and peroxynitrite (ONOO−) were conducted before and during the therapy. We found that the plasma concentrations of oxidative stress markers, such as O2– and H2O2, are higher in preeclampsia and positively correlated with the MAP value. Moreover, it was shown that the plasma concentration of NO2– as an indicator of NO levels is higher in preeclampsia. A short-term intramuscular application of estradiol decreases the MAP value and the plasma concentration of O.–, H2O2, NO2−, and ONOO– in preeclampsia. A positive correlation between the decrease of MAP values and the decrease of plasma concentrations of O2–, H2O2, and ONOO– was found in preeclampsia during a short-term estradiol therapy. We conclude that the short-term estradiol therapy decreases the MAP value in preeclampsia by modulating the plasma oxidative stress. We speculate that the estradiol metabolism in preeclampsia is an important mechanism that contributes to vascular dysfunction.

© 2018 Taylor  &  Francis. Mechanisms of platelet activation are triggered by thrombin, adenosine diphosphate (ADP), epinephrine, thromboxane A2, and other soluble agonists which induce signaling via heterotrimeric Gαq, Gαi, and Gα12/13 proteins. We have undertaken a study addressing the contribution of these G proteins to platelet activation and clot formation in the presence of eptifibatide, thus excluding outside-in signaling provided by integrin αIIbβ3–fibrinogen engagement. Selective and combined activation of the G proteins was achieved by using combinations of platelet agonists and inhibitors. Platelet activation in platelet-rich plasma was evaluated by P-selectin expression using flow cytometry. Contribution of platelets to whole blood clotting was assessed by rotation thromboelastometry (ROTEM). Selective signaling of Gαq or Gαi but not Gα12/13 promoted P-selectin expression. Further enhancement of P-selectin expression was achieved by ADP-induced combined signaling of Gαq and Gαi, and to more extent by U46619 at high concentration (1.5 μM) induced combined signaling of Gαq and Gα12/13 while maximal P-selectin expression was achieved by thrombin receptor-activating peptide (TRAP)-induced combined signaling of Gαq, Gαi, and Gα12/13. In ROTEM, selective activation of Gαq, Gαi, or Gα12/13 failed to affect blood clotting. Combined signaling of Gαq and Gαi or Gαq and Gα12/13 or all three G proteins shortened the clotting time and stimulated clot strength. Pretreatment of platelets with acetylsalicylic acid did not change the effect of ADP but inhibited the effect of TRAP. Signaling of Gαq and Gα12/13 triggered by U46619 also stimulated clot formation. Combined signaling of either Gαq and Gαi or Gαq and Gα12/13 is sufficient to stimulate maximal platelet activation and enhanced clot formation in platelets treated with inhibitor of integrin αIIbβ3. It could be suggested that outside-in signaling is not necessarily required to fulfill these platelet functions.

© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd. Background: Elevated levels of C-reactive protein (CRP), a sensitive marker of inflammation, have been consistently reported in chronic spontaneous urticaria (CSU). Here, we retrospectively analyzed data from 1253 CSU patients from 2 centers to answer the following questions: (i) What is the prevalence of elevated levels of CRP in CSU? (ii) Why do CSU patients show elevated levels of CRP? (iii) Are elevated CRP levels relevant?. Methods: Serum levels of CRP were measured by the nephelometric method. We collected information regarding various laboratory tests including ESR, CBC with differential, D-dimer, fibrinogen, C3, C4, IL-6, etc. For most patients, we also collected data on age, gender, duration of CSU, presence of angioedema, activity (UAS at the time of blood sampling and for 7 days), quality of life (CU-Q2oL and/or DLQI), comorbidities and possible causes of CSU, and autologous serum skin test (ASST) response. The efficacy of second-generation antihistamines was evaluated on the day of blood collecting. Results: One-third of CSU patients had elevated levels of CRP. Higher levels of CRP were associated with ASST positivity (P =.009) and arterial hypertension (P =.005), but not with other possible causes or comorbidities of CSU. C-reactive protein correlated with urticaria activity (P <.001), quality of life impairment (P =.026), and inflammatory and coagulation markers (P <.001). C-reactive protein levels were significantly higher in nonresponders to antihistamines as compared to responders (P <.001). Conclusion: Elevated levels of CRP are common and relevant in CSU patients. The assessment of CRP levels may help to optimize the management of patients with CSU.

© 2018 Elsevier B.V. Phylodynamics of Crimean Congo Hemorrhagic fever virus (CCHFV) genotype V in South Russia was analyzed using 244 partial (452–571 nt) sequences in all three genomic segments and 38 complete genomic sequences. Despite increased number of sequences, the Russian lineage of the European genotype V (commonly termed GtVa) was distinct from GtV isolates from Turkey and the Balkan countries. No geographic pattern was observed in phylogenetic subgrouping of CCHFV within South Russia. Identical isolates could be found at distant locations spaced by hundreds of kilometers, while relatively divergent viruses circulated in the same region. Full genome analysis indicated that reassortment events within GtVa occurred every few decades (median half-life of a non-reassortant node 30–40 years) and involved M and S segments. Therefore, in South Russia CCHFV represents a highly dynamic population of frequently reassorting viruses.

© 2017, European Biophysical Societies' Association. The Smoluchowski equation with an energy profile of a special type and an assumed hydrophobic (“half”) pore source term is used to describe the process of hydrophilic pore formation in a lipid bilayer at the gel-liquid phase transition. The source term reflects the occurrence of molecule packing defects in a lipid bilayer at phase transition. The time sequences of the pore formation and closure events are treated as non-stationary, second-order Erlang flows whose characteristics depend on the equation solution. The computed distributions of the time intervals between hydrophilic pores, and pore lifetimes agree with the previously published experimental interpulse interval and pulse duration histograms for the current fluctuations through planar bilayer membranes of DPPC immersed in a LiCl aqueous solution containing polyethylene glycol. Thus, the statistical analysis of pore formation and closure times leads us to conclude that firstly, the increased permeability of a lipid bilayer during the gel-liquid phase transition is accounted for by the emergence of additional hydrophobic defects in the heterogeneous structure of the bilayer and secondly, that the non-exponential distributions of the lipid channel closed and open times observed in experiments are evidence that the process of hydrophilic pore formation is not a one-step process but involves at least two dependent events.

© 2018 Osipov, Machneva, Buravlev and Vladimirov. The biological roles of heme and nonheme nitrosyl complexes in physiological and pathophysiological conditions as metabolic key players are considered in this study. Two main physiological functions of protein nitrosyl complexes are discussed-(1) a depot and potential source of free nitric oxide (NO) and (2) a controller of crucial metabolic processes. The first function is realized through the photolysis of nitrosyl complexes (of hemoglobin, cytochrome c, or mitochondrial iron-sulfur proteins). This reaction produces free NO and subsequent events are due to the NO physiological functions. The second function is implemented by the possibility of NO to bind heme and nonheme proteins and produce corresponding nitrosyl complexes. Enzyme nitrosyl complex formation usually results in the inhibition (or enhancement in the case of guanylate cyclase) of its enzymatic activity. Photolysis of protein nitrosyl complexes, in this case, will restore the original enzymatic activity. Thus, cytochrome c acquires peroxidase activity in the presence of anionic phospholipids, and this phenomenon can be assumed as a key step in the programmed cell death. Addition of NO induces the formation of cytochrome c nitrosyl complexes, inhibits its peroxidase activity, and hinders apoptotic reactions. In this case, photolysis of cytochrome c nitrosyl complexes will reactivate cytochrome c peroxidase activity and speed up apoptosis. Control of mitochondrial respiration by NO by formation or photolytic decay of iron-sulfur protein nitrosyl complexes is an effective instrument to modulate mitochondrial metabolism. These questions are under discussion in this study.

©2018 Osipov, Machneva, Buravlev and Vladimirov. The biological roles of heme and nonheme nitrosyl complexes in physiological and pathophysiological conditions as metabolic key players are considered in this study. Two main physiological functions of protein nitrosyl complexes are discussed-(1) a depot and potential source of free nitric oxide (NO) and (2) a controller of crucial metabolic processes. The first function is realized through the photolysis of nitrosyl complexes (of hemoglobin, cytochrome c, or mitochondrial iron-sulfur proteins). This reaction produces free NO and subsequent events are due to the NO physiological functions. The second function is implemented by the possibility of NO to bind heme and nonheme proteins and produce corresponding nitrosyl complexes. Enzyme nitrosyl complex formation usually results in the inhibition (or enhancement in the case of guanylate cyclase) of its enzymatic activity. Photolysis of protein nitrosyl complexes, in this case, will restore the original enzymatic activity. Thus, cytochrome c acquires peroxidase activity in the presence of anionic phospholipids, and this phenomenon can be assumed as a key step in the programmed cell death. Addition of NO induces the formation of cytochrome c nitrosyl complexes, inhibits its peroxidase activity, and hinders apoptotic reactions. In this case, photolysis of cytochrome c nitrosyl complexes will reactivate cytochrome c peroxidase activity and speed up apoptosis. Control of mitochondrial respiration by NO by formation or photolytic decay of iron-sulfur protein nitrosyl complexes is an effective instrument to modulate mitochondrial metabolism. These questions are under discussion in this study.

© 2018, Pleiades Publishing, Ltd. Mediator is a key factor in the regulation of expression of RNA polymerase II-transcribed genes. Recent studies have shown that Mediator acts as a coordinator of transcription activation and participates in maintaining chromatin architecture in the cell nucleus. In this review, we present current concepts on the structure and functions of Mediator.

© The Author(s) 2018. Earlier studies have shown that combination of antibodies to S100 protein and to cannabinoid receptor type 1 in released-active form (Brizantin) may possess anxiolytic properties and decrease nicotine dependence. Released-active form of antibodies is a novel approach that permits to modify natural functions of the target molecule (antigen) under investigation. The aim of the present study was to evaluate the anxiolytic-like effect of Brizantin in the light–dark test in mice, according to its ability to influence the number of entries into the lit compartment and the total time spent there. Three doses of Brizantin (2.5, 5, and 10 mL/kg) were compared with diazepam (1 mg/kg), placebo, and vehicle control. Anxiolytic-like effect of the tested drug was shown to be dose dependent, with an increasing trend from 2.5 to 10 mL/kg. Brizantin in its highest dose significantly increased studied behavioral parameters, although its effect was less pronounced than that of the reference drug diazepam (1 mg/kg).

© 2018 by the authors. Licensee MDPI, Basel, Switzerland.  Wild ducks are known to be able to carry avian influenza viruses over long distances and infect domestic ducks, which in their turn infect domestic chickens. Therefore, prevention of virus transmission between ducks and chickens is important to control the spread of avian influenza. Here we used a low pathogenic wild aquatic bird virus A/duck/Moscow/4182/2010 (H5N3) for prevention of highly pathogenic avian influenza virus (HPAIV) transmission between ducks and chickens. We first confirmed that the ducks orally infected with H5N1 HPAIV A/chicken/Kurgan/3/2005 excreted the virus in feces. All chickens that were in contact with the infected ducks became sick, excreted the virus, and died. However, the ducks orally inoculated with 10 4 50% tissue culture infective doses of A/duck/Moscow/4182/2010 and challenged 14 to 90 days later with H5N1 HPAIV did not excrete the challenge virus. All contact chickens survived and did not excrete the virus. Our results suggest that low pathogenic virus of wild aquatic birds can be used for prevention of transmission of H5N1 viruses between ducks and chickens.

© 2018 Elsevier B.V. Background: Very recently, a novel European hantavirus, Sochi virus, has been discovered which causes severe courses of hantavirus disease with a case fatality rate of about 15 percent. Objectives: We aimed to study to which extent and with which clinical severity children were affected by Sochi virus infection. Study design: Sochi virus infection of patients was confirmed by molecular, serological, and epizoonotic studies. Clinical and laboratory parameters were analyzed for the age group of up to 15 years (n = 6) in comparison to all older patients (n = 56). Results: 9.7 percent of patients with hantavirus disease studied (6/62) were up to 15 years old. The children showed moderate to severe clinical courses similarly to the situation in adults. Conclusions: While children are in general considered to be less affected by hantavirus infections than adults, in case of highly pathogenic hantaviruses, such as Sochi virus, frequency of clinical cases as well as their clinical course are comparable between children and adults. Therefore, hantavirus disease, particularly in regions endemic to highly pathogenic hantaviruses, should be considered in cases of unclear fever and kidney/pulmonary failure in children.

© 2017 John Wiley  &  Sons Ltd and International Behavioural and Neural Genetics Society  Anxiety disorders result from a complex interplay of genetic and environmental factors such as stress. On the level of cellular signaling, regulator of G protein signaling 2 (Rgs2) has been implicated in human and rodent anxiety. However, there is limited knowledge about the role of Rgs2 in fear learning and reactivity to stress. In this study, Rgs2 −/− mice showed increased fear learning, male mice displayed increased contextual and cued fear learning, while females showed selectively enhanced cued fear learning. Male Rgs2 −/− mice displayed increased long-term-contextual fear memory, but increased cued fear extinction. Learning in spatial non-aversive paradigms was also increased in Rgs2 −/− mice. Female, but not male mice show increased spatial learning in the Barnes maze, while male mice showed enhanced place preference in the IntelliCage, rendering enhanced cognitive function non-specific for aversive stimuli. Consistent with the previous results, Rgs2 deletion resulted in increased innate anxiety, including neophobic behavior expressed as hypolocomotion, in three different tests based on the approach-avoidance conflict. Acute electric foot shock stress provoked hypolocomotion in several exploration-based tests, suggesting fear generalization in both genotypes. Rgs2 deletion was associated with reduced monoaminergic neurotransmitter levels in the hippocampus and prefrontal cortex and disturbed corresponding GPCR expression of the adrenergic, serotonergic, dopaminergic and neuropeptide Y system. Taken together, Rgs2 deletion promotes improved cognitive function as well as increased anxiety-like behavior, but has no effect on acute stress reactivity. These effects may be related to the observed disruption of the monoaminergic systems.

© 2018 S. Karger AG, Basel. Asthma is a chronic disabling respiratory disease that can be triggered by a variety of factors, including allergens, respiratory infections, psychological factors, occupational agents, exercise, atmospheric pollutants, and drugs. The asthma syndrome has been treated for decades according to a "one-fits-all" treatment strategy based on bronchodilators and steroids. With the availability of new forms of treatment targeting the different pathomechanisms of the asthma syndrome, such as anti-immunoglobulin E and cytokine-targeting therapies, the interest in biomarkers that can dis criminate different forms of asthma according to their pathomechanisms has increased. This review attempts to provide an overview of protein biomarkers in asthma and how they might be used to discriminate different forms of asthma that may respond positively to sophisticated new targeted therapies.

© 2018 Fedoros et al. Identification of molecular targets and mechanism of action is always a challenge, in particular - for natural compounds due to inherent chemical complexity. BP-Cx-1 is a water-soluble modification of hydrolyzed lignin used as the platform for a portfolio of innovative pharmacological products aimed for therapy and supportive care of oncological patients. The present study describes a new approach, which combines in vitro screening of potential molecular targets for BP-Cx-1 using Diversity Profile - P9 panel by Eurofins Cerep (France) with a search of possible active components in silico in ChEMBL - manually curated chemical database of bioactive molecules with drug-like properties. The results of diversity assay demonstrate that BP-Cx-1 has multiple biological effects on neurotransmitters receptors, ligand-gated ion channels and transporters. Of particular importance is that the major part of identified molecular targets are involved in modulation of inflammation and immune response and might be related to tumorigenesis. Characterization of molecular composition of BP-Cx-1 with Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and subsequent identification of possible active components by searching for molecular matches in silico in ChEMBL indicated polyphenolic components, nominally, flavonoids, sapogenins, phenanthrenes, as the major carriers of biological activity of BP-Cx-1. In vitro and in silico target screening yielded overlapping lists of proteins: adenosine receptors, dopamine receptor DRD4, glucocorticoid receptor, serotonin receptor 5-HT1, prostaglandin receptors, muscarinic cholinergic receptor, GABAA receptor. The pleiotropic molecular activities of polyphenolic components are beneficial in treatment of multifactorial disorders such as diseases associated with chronic inflammation and cancer.

© 2018 Informa UK Limited, trading as Taylor  &  Francis Group Objective: The aim of this case series is to raise awareness of obstetric-related atypical haemolytic uraemic syndrome (aHUS) amongst obstetricians and gynaecologists. Study design: Data from 20 consecutive patients, aged 19–38, with obstetric-aHUS manifestation during or immediately after pregnancy are reported. Patients were diagnosed and treatment was initiated between 2012 and 2016. Results: Presentation of aHUS was mainly preceded by preeclampsia and/or haemolysis, elevated liver enzymes and low platelet count syndrome, other obstetric complications, or by diarrhoea. Thrombotic microangiopathy (TMA) was evident in all patients with signs of microangiopathic haemolysis (sharp decline in haemoglobin; mean 67 g/L), elevated lactate dehydrogenase (LDH; mean 2953.1 U/L), schistocytosis, thrombocytopenia (mean platelet count 52.5 × 109/µL), and acute kidney injury (AKI) (hypercreatininaemia, mean 456.4 µmol/L; oliguria or anuria). The majority of patients (80%) initially presented with arterial hypertension. Diagnosis of obstetric-aHUS was complicated, as multiple organs were affected. Time taken to make the diagnosis of aHUS delayed the initiation of fresh-frozen plasma infusions and plasma exchange (80% of patients) and subsequent eculizumab treatment (40% of patients). Maternal mortality was high (35%) as was foetal mortality (25%). Conclusions: Obstetric-aHUS is a serious condition characterized by multiple organ failure (MOF) and a high mortality rate. Presentation of obstetric-aHUS is preceded by various precipitating factors, suggesting pregnancy complications, and not the pregnancy per se, often induce aHUS in women with a genetic predisposition to its development. A delay in the correct diagnosis and initiation of the most effective treatment can have serious consequences, reinforcing the need to raise awareness of obstetric-aHUS.

© 2017 Elsevier B.V. KISS1 tumor suppressor protein regulates cancer cell invasion via MMP9 metalloproteinase. Downregulation of KISS1 gene expression promotes progression of breast cancer and melanoma, resulting in the development of distant metastases. In the current study, we investigated whether restoration of KISS1 expression in KISS1-deficient human metastatic breast cancer cells holds potential as an advanced anticancer strategy. To this end we engineered an infectivity-enhanced conditionally-replicative human adenovirus type 5 encoding KISS1 as an “arming” transgene in the Ad5 E3 region for an ectopic KISS1 expression in transduced cancer cells. The oncolytic potential of the vector was examined using brain-invading metastatic clones of CN34 and MDA-MB-231 breast cancer cells, which supported high levels of AdKISS1 replication, correlating with a robust CRAd-mediated cytotoxicity. Secretion of cellular factors responsible for tumor angiogenesis, cell-to-cell communication and anti-tumoral immune responses upon KISS1 expression in breast cancer cells was analyzed by a RayBiotech Kiloplex Quantibody array. Overall, our results indicate that KISS1 transgene expression provides an important benefit for CRAd-mediated cytotoxicity in breast cancer cells and holds potential as an anticancer treatment in conjunction with oncolytic virotherapy of breast and other metastatic cancers.