Molecular cloning of KS, a novel rat gene expressed exclusively in the kidney

Molecular cloning of xKSx, a novel rat gene expressed exclusively in the kidney.BackgroundWe aimed to identify genes with kidney specific, developmentally regulated expression. Here we report the cDNA sequence and expression pattern of KS, a novel kidney-specific rat gene.MethodsA partial cDNA was identified by differential display polymerase chain reaction (PCR) of a renal cell fraction enriched for proximal tubular and renin-expressing cells. Using the partial cDNA as a probe, a rat kidney cDNA library was screened. The full-length KS sequence was obtained by PCR amplification of cDNA ends. The expression pattern of KS was investigated by Northern blot. RNA was extracted from several organs of newborn and adult rats, as well as from the kidneys of rats with altered tubular function, that is, rats that had undergone unilateral nephrectomy, unilateral ureteral obstruction, neonatal losartan treatment, and the appropriate control animals. The expression of KS was also investigated in the kidneys of rats with spontaneous or renovascular hypertension.ResultsThe KS cDNA (2426bp) contained one open reading frame encoding a predicted 572 amino acid protein. The derived peptide sequence displayed approximately 70% similarity to the hypertension-related SA gene product and approximately 50% similarity to prokaryotic and eukaryotic acetyl-CoA synthases (EC 6.2.1.1). KS was expressed in the kidney and not in any other organ assayed. KS RNA was not detected in fetal and newborn rat kidney but became apparent after one week of postnatal life. Gene expression was downregulated in rat models of altered tubular function. KS expression was decreased in spontaneously hypertensive rats but not in renovascular hypertension.ConclusionKS, a novel rat gene, exhibits a unique tissue-specific expression exclusively in mature kidneys. The data suggest KS may encode an adenosine monophosphate binding enzyme

PFKFB3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse

Introduction: Circulating monocytes are main source for tumor-associated macrophages (TAMs) that control tumor growth, angiogenesis, metastasis and therapy resistance. We raised the questions how monocyte programming is affected by growing tumors localized in colon and rectal sections, and how treatment onsets affect monocyte programming in the circulation. Methods: Patients with rectal cancer and colon cancer were enrolled in the study. Peripheral blood monocytes were characterized by phenotypic analysis using flow cytometry, by transcriptomic analysis using RNA sequencing and by gene expression analysis using real-time RT-PCR. Phenotypic analysis was performed with IF/confocal microscopy. Spatial transcriptomic analysis was applied using GeoMX DSP-NGS. Results: In patients with rectal cancer, increased amount of CCR2+ monocytes was indicative for the absence of both lymphatic and hematogenous metastasis. In contrast, in patients with colon cancer CD163+ monocytes were indicative for LN metastasis. NGS analysis identified tumor-specific transcriptional programming of monocytes in all CRC patients compared to healthy individuals. The key transcriptional difference between monocytes of patients with colon and rectal cancer was increased expression of PFKFB3, activator of glycolysis that is currently considered as therapy target for major solid cancers. PFKFB3-expressing monocyte-derived macrophages massively infiltrated tumor in colon. Nanostring technology identified correlation of PFKFB3 with amount and tumor-promoting properties of TAMs in colon but not in rectal cancer. PFKFB3 was indicative for tumor relapse specifically in colon cancer. Discussion: Our findings provide essential argument towards CRC definition to cover two clinically distinct cancers – colon cancer and rectal cancer, that differentially interact with innate immunity

Сравнение подходов к реализации образовательных программ по направлению "бизнес-информатика" в России и Германии

Business informatics is a relatively young academic discipline. During the last years several efforts have been made to compare the German discipline Wirtschaftsinformatik with the Anglo-American sister discipline information systems. However, these studies have mainly focused on research activities; they have not attempted to compare curricula in both disciplines. With the change of the political and economic system in the former Soviet Union and the introduction of courses of studies in business informatics in Russia it may be helpful to compare the German with the Russian approach to teaching business informatics. The objective of this paper is to compare bachelor studies in business informatics at selected universities in Russia and Germany. This paper contains the outline of the history of business informatics as a scientific discipline in Russia and Germany, a description of professional organizations, standards, and guidelines relevant for business informatics in both countries. Special attention is given to an overview of students studying business informatics, a description of time scales and grading scales and the structure of teaching plans in Russia and Germany. The paper contains the explanation of the method used to analyze and compare bachelor studies at ten German and ten Russian universities. Findings of the analysis concern details of bachelor studies in business informatics at German and Russian universities and highlight similarities and differences

Первичный серологический статус и иммунологическая эффективность вакцинации против Streptococcus pneumoniae и Haemophilus influenzae типа b у детей с бронхолегочной дисплазией: когортное исследование

Background. The primary serological status of children with bronchopulmonary dysplasia (BPD) with respect to respiratory significant pathogens remains unstudied. Wherein, the efficacy of vaccination of children with BPD against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) has been studied in a small number of studies which results are contradictory.Objective. Our aim was to study the pre-vaccinal serological status with regard to S. pneumoniae and Hib and the immunological efficacy of vaccination against these infections in children with BPD.Methods. The study included children with BPD without exacerbation. The immunological efficacy of conjugate vaccines — pneumococcal 13-valent and against Haemophilus influenza type b — was assessed by the level of IgG against S. pneumoniae and Hib using the ELISA method. The level of antibodies was determined before vaccination and 1 or 3–6 months afterwards.Results. The study included 32 children with BPD, mean age at the time of determining primary serological status was 13.3±1.3 months, at the time of vaccination — 15.2±1.5 months. The mean gestational age was 28.7±0.8 weeks, the body weight at birth was 1225±180 g. Before vaccination, all children with BPD had no protective antibody titre against S. pneumoniae and Hib averaging 0.2±0.034 and 0.13±0.0106 mg/L, respectively. One month after vaccination, the level of antibodies to S. pneumoniae reached 12.9±2.34 mg/L to Hib — 3.34±0.769 mg/L.Conclusion. After immunization with a pneumococcal 13-valent conjugate vaccine and a conjugate vaccine against Haemophilus influenzae type b, the concentration of IgG against S. pneumoniae exceeded the protective level in all examined patients (100%), the concentration to Hib — in 29 (90.6%).Обоснование. Первичный серологический статус детей с бронхолегочной дисплазией (БЛД) в отношении респираторно значимых патогенов остается неизученным. При этом эффективность вакцинации детей с БЛД против Streptococcus pneumoniae и Haemophilus influenzae типа b (Hib) изучалась в небольшом числе исследований, результаты которых противоречивы. Цель исследования — изучить довакцинальный серологический статус в отношении S. pneumoniae и Hib и иммунологическую эффективность вакцинации против этих инфекций у детей с БЛД.Методы. В исследование включали детей с БЛД, вне обострения. Иммунологическую эффективность конъюгированных вакцин — 13-валентной пневмококковой и против гемофильной инфекции типа b — оценивали по уровню IgG к S. pneumoniae и Hib методом ELISA. Уровень антител определяли до вакцинации и спустя 1 и 3–6 мес.Результаты. Включено 32 ребенка с БЛД средний возраст которых на момент определения первичного серологического статуса составил 13,3±1,3 мес, на момент вакцинации — 15,2±1,5 мес. Средний гестационный возраст — 28,7±0,8 нед, масса тела при рождении — 1225±180 г. У всех детей с БЛД до вакцинации отсутствовал защитный титр антител к S. pneumoniae и Hib, составив в среднем 0,2±0,034 и 0,13±0,0106 мг/л соответственно. Через 1 мес после вакцинации уровень антител к S. pneumoniae достигал 12,9±2,34 мг/л, к Hib — 3,34±0,769 мг/л.Заключение. После иммунизации 13-валентной пневмококковой конъюгированной вакциной и конъюгированной вакциной против гемофильной инфекции типа b концентрация IgG к S. pneumoniae превышала защитный уровень у всех обследованных пациентов (100%), концентрация к Hib — у 29 (90,6%).Конфликт интересовЛ.С. Намазова-Баранова — получение исследовательских грантов от фармацевтических компаний Пьер Фабр, Genzyme Europe B.V., ООО «Астра зенека Фармасьютикалз», Gilead / PRA «Фармасьютикал Рисерч Ассошиэйтс СиАйЭс», Teva Branded Pharma ceuti cal products R&D, Inc. / ООО «ППД Девелопмент (Смоленск)», «Сталлержен С.А.» / «Квинтайлс ГезмбХ» (Австрия). М.В. Федосеенко — получение гонораров от компании Sanofi, Pfizer за чтение лекций

Results of the COVID-19 mental health international for the general population (COMET-G) study.

INTRODUCTION: There are few published empirical data on the effects of COVID-19 on mental health, and until now, there is no large international study. MATERIAL AND METHODS: During the COVID-19 pandemic, an online questionnaire gathered data from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively. STATISTICAL ANALYSIS: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses and Factorial Analysis of Variance (ANOVA) tested relations among variables. RESULTS: Probable depression was detected in 17.80% and distress in 16.71%. A significant percentage reported a deterioration in mental state, family dynamics and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (31.82% vs. 13.07%). At least half of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop depression was associated with history of Bipolar disorder and self-harm/attempts (RR = 5.88). Suicidality was not increased in persons without a history of any mental disorder. Based on these results a model was developed. CONCLUSIONS: The final model revealed multiple vulnerabilities and an interplay leading from simple anxiety to probable depression and suicidality through distress. This could be of practical utility since many of these factors are modifiable. Future research and interventions should specifically focus on them

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Background: Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. Methods: The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. Findings: Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. Interpretation: In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. Funding: Novo Nordisk

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe

Superconducting Diode Effect in Topological Hybrid Structures

Currently, the superconducting diode effect (SDE) is being actively discussed, due to its large application potential in superconducting electronics. In particular, superconducting hybrid structures, based on three-dimensional (3D) topological insulators, are among the best candidates, due to their having the strongest spin–orbit coupling (SOC). Most theoretical studies on the SDE focus either on a full numerical calculation, which is often rather complicated, or on the phenomenological approach. In the present paper, we compare the linearized and nonlinear microscopic approaches in the superconductor/ferromagnet/3D topological insulator (S/F/TI) hybrid structure. Employing the quasiclassical Green’s function formalism we solve the problem self-consistently. We show that the results obtained by the linearized approximation are not qualitatively different from the nonlinear solution. The main distinction in the results between the two methods was quantitative, i.e., they yielded different supercurrent amplitudes. However, when calculating the so-called diode quality factor the quantitative difference is eliminated and both approaches result in good agreement