Toponymy of Kalmykia in Historical, Geographical and Linguistic Perspectives. Review of the book: Kichikova, N. A., Mandzhieva, E. B., & Suprun, V. I. (2017). Toponimicheskii slovar’ Respubliki Kalmykiia [Toponymic Dictionary of the Republic of Kalmykia]. Elista: Dzhangar. 272 p.

The reviewed book analyzes the toponymic vocabulary of the Republic of Kalmykia — a Russian region that retains a number of historical, geographical, administrative and territorial peculiarities. A centuries-old history of the region mapped since Herodotus times, around 5th century BC, its unique position on the plane in the semi-desert zone, the richness of its flora and fauna, as well the nomadic life of the K almyks which remained true until quite recently — have cumulatively left their mark on the specificity of geographical names included into this dictionary of more than 300 entries. The dictionary contains names of cities and towns, working-class settlements, villages, and other habitats, as well as names of rivers, lakes, elevations, ravines, gullies and other geographical objects of the Republic of Kalmykia. The structure of the dictionary is rather simple. It opens with an extended preface followed by the lexicographic part that is alphabetically arranged, the list of sources and a few elaborative lists to help using the dictionary. An appendix containing data on the numbers of residents in various localities of Kalmykia according to the 2017 census is presented in the end. Each entry includes physical, economic and geographical characteristic of the named object complete with linguistic and linguocultural information about the toponym and its etymological interpretations. The dictionary presents an exemplary case for the description of toponymic vocabulary of other Russian regions, including that of various nations residing on the territory of the Russian Federation. The edition itself represents a considerable contribution to the regional onomastic lexicography

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

EPISTOLARY STYLE AS AN OBJECT OF A LINGUOCULTUROLOGICAL RESEARCH

The article highlights some peculiarities of epistolary colloquial speech, registered in a business- and-friendly written dialogue of the Russian creative intelligentsia in the late 20 th century. The material for this scientific consideration were some letters of A.V. Makedonov, a Smolensk-born literary historian, critic and publicist addressed to Yu. V. Pashkov, a Smolensk poet, whose literary talent A.V. Makedonov always wished to support; the letters, which have never been under study, are available at Smolensk University Literary Museum Archive. A complex analysis of the epistolary style in the letters by A.V. Makedonov was based on the communicative- and-pragmatic and linguoculturological approaches and directed at reconstruction of a speech portrait with regard to the several levels of speech personality, in particular, the semantic level, which characterizes the epistolary style as a written form of colloquial speech, the linguo-cognitive level, that singles out epistolary concepts conductive to informational and assessment aspects of the letters, and the motivation level, which implies analysis of speech acts and speech-etiquette standards in the letters, makes it possible to single out several peculiarities of the communicants’ inter-relations on a par with their personal characteristics. In conclusion the article sums up epistolary stylistic peculiarities of A.V. Makedonov’s creative personality and speech culture

Развитие процессов слухового анализа у пользователей кохлеарных имплантов с применением программных средств

Introduction. Modern technology for auditory prostheses (digital hearing aids, cochlear implantation) creates conditions for auditory rehabilitation of individuals with severe hearing loss and even deafness. In this case, the important task of developing and updating sensory experiences arises, including the formation of the primary auditory–speech analysis processes, the consolidation of new intersensory connections, and the mechanisms of auditory–motor integration, which form the basis for communication and cognitive activity under new interactions with the environment. An effective solution to this psychophysiological problem can be facilitated by using specialized software that provides a targeted training of the perception skills necessary to implement the function of auditory–speech communication in patients with hearing impairments and by objective assessment of the individual progress of their rehabilitation using psychophysical methods. This study aimed to test the effectiveness of using software in sophisticated situations of rehabilitation after cochlear implantation. Methods. The specially designed software tools were used to develop the processes of auditory analysis of perception and speech in cochlear implant users of different ages with pre- and post-lingual deafness. The results were assessed according to psychophysical testing based on quantitative indicators of correct recognition and reaction time. Three series of the study were related to the following sophisticated rehabilitation situations: (a) late implantation (n = 32), (b) auditory analysis of dynamic signals during the perception of prosodic information in speech (n = 36), and (c) in conditions of spatial orientation (n = 25). Results. New data and the results of their comparison indicated a significant improvement in the detection and analysis of basic spectral-temporal features of non-speech and speech signals (interruption by a pause, change in a rhythmic pattern of sound stimulation, location and movement of the sound source, phonetic categories and prosodic characteristics of speech), as well as the use of auditory–speech skills by cochlear implant users in everyday situations after training. Discussion. In general, experience in the practical use of software tools indicates that it is advantageous to integrate them into methodological tools for cochlear implant centers and auditory training in the education of children with hearing impairments.Введение. Современные технологии слухопротезирования (супермощные цифровые слуховые аппараты, кохлеарная имплантация) создают условия для слуховой реабилитации людей с большими потерями слуха и даже глухотой. При этом возникает актуальная задача развития и обновления сенсорного опыта, включая формирование первичных процессов слухоречевого анализа с закреплением новых межсенсорных связей и механизмов слухомоторной интеграции как основы коммуникативной и когнитивной деятельности в новых условиях взаимодействия с окружающей средой. Эффективному решению этой психофизиологической задачи может способствовать применение специализированных программных средств, предоставляющих возможность направленной тренировки перцептивных навыков, необходимых для реализации слухоречевой функции пациентов с нарушениями слуха, и объективной оценки индивидуальной динамики их реабилитации методами психофизики. Целью исследования стала проверка эффективности использования программных средств в проблемных ситуациях реабилитации после кохлеарной имплантации. Методы. Разработанные программные средства применяли для развития процессов слухового анализа восприятия и речи у пользователей кохлеарных имплантов разного возраста с до- и постлингвальной глухотой. Результаты оценивали по данным психофизического тестирования на основе количественных показателей правильного распознавания и времени реакции. Три серии исследования отражали проблемные ситуации реабилитации: поздняя имплантация (n = 32); слуховой анализ динамических сигналов при восприятии просодической информации в речи (n = 36) и в условиях пространственной ориентации (n = 25). Результаты. Новые данные и результаты их сравнения свидетельствовали о достоверном улучшении в обнаружении и анализе базовых спектрально-временных признаков неречевых и речевых сигналов (прерывание паузой, изменение ритмического рисунка звуковой стимуляции, локализация и движение источника звука, фонетические категории и просодические характеристики речи), а также в использовании пользователями кохлеарных имплантов слухоречевых навыков в повседневных ситуациях после тренировки. Обсуждение результатов. В целом, опыт практического применения программных средств свидетельствует о целесообразности их включения в методический инструментарий центров кохлеарной имплантации и коррекционной работы при обучении детей с нарушенным слухом

Biocompatibility of Small-Diameter Vascular Grafts in Different Modes of RGD Modification

Modification with Arg-Gly-Asp (RGD) peptides is a promising approach to improve biocompatibility of small-calibre vascular grafts but it is unknown how different RGD sequence composition impacts graft performance. Here we manufactured 1.5 mm poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) grafts modified by distinct linear or cyclic RGD peptides immobilized by short or long amine linker arms. Modified vascular prostheses were tested in vitro to assess their mechanical properties, hemocompatibility, thrombogenicity and endothelialisation. We also implanted these grafts into rat abdominal aortas with the following histological examination at 1 and 3 months to evaluate their primary patency, cellular composition and detect possible calcification. Our results demonstrated that all modes of RGD modification reduce ultimate tensile strength of the grafts. Modification of prostheses does not cause haemolysis upon the contact with modified grafts, yet all the RGD-treated grafts display a tendency to promote platelet aggregation in comparison with unmodified counterparts. In vivo findings identify that cyclic Arg-Gly-Asp-Phe-Lys peptide in combination with trioxa-1,13-tridecanediamine linker group substantially improve graft biocompatibility. To conclude, here we for the first time compared synthetic small-diameter vascular prostheses with different modes of RGD modification. We suggest our graft modification regimen as enhancing graft performance and thus recommend it for future use in tissue engineering

Human tankyrases are aberrantly expressed in colon tumors and contain multiple epitopes that induce humoral and cellular immune responses in cancer patients

PURPOSE: Tankyrases 1 and 2 are telomere-associated poly(ADP-ribose) polymerases (PARP) that can positively regulate telomere elongation and interact with multiple cellular proteins. Recent reports implicated tankyrases as tumor antigens and potential targets of anticancer treatment. We examined expression of tankyrases in colon tumors and immune response to these enzymes in patients with different types of cancer. METHODS: mRNA and protein expression was evaluated by quantitative real-time RT-PCR and Western blotting, respectively. Humoral immune response to recombinant tankyrases was investigated by modified enzyme-linked immunoassays. Cellular immune response was analysed by ELISPOT and (51)Cr release assays. RESULTS: We found that both mRNA and protein levels of tankyrase 2 (TNKL) are upregulated in colon tumors. In contrast, protein level of tankyrase 1 (TNKS) is downregulated, while mRNA level shows variable changes. More than a quarter of colon cancer patients develop humoral immune response to at least one of the two tankyrases. In this study we mapped common and unique B-cell epitopes located in different domains of the two proteins. Additionally, we present evidence for T-cell responses both to epitopes that are unique for TNKL and to those shared between TNKL and TNKS. CONCLUSION: Our study favors a biomarker usage of antibody response to tankyrases. Spontaneous CD8(+) T-cell responses to these enzymes are rare and further investigation is needed to evaluate tankyrases as potential targets for cancer immunotherapy

Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting & Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (<60, 60-69, and >_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 & PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages <60, 60-69, and >_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791