Investigation of the Heating Processes and Temperature Field of the Frequency-controlled Asynchronous Engine Based on Mathematical Models

The study of the temperature field of the engine for non-stationary modes is done. A numerical simulation of a non-stationary thermal process using dynamic EHD, the characteristic of the rate of rise of temperatures is done. An increase in the temperature of individual parts in the idle interval, when the power of heat release is significantly reduced, is established, and the reverse of the heat flow through the air gap is established. It is shown that the EHD method, in contrast to the FEM, is self-sufficient, which determines its practical value. In various parts of the speed control range in the implementation of various laws of regulation. At the same time, the main electrical, magnetic and additional losses associated with the fundamental voltage harmonics (FVH), and mechanical losses, as well as additional electrical and magnetic losses associated with the higher voltage harmonics, change. When using serial asynchronous engines as frequency-controlled. Permissible under the conditions of heating power is significantly reduced by the power of serial engines. Depending on the synchronous speed, the reduction is from 10 % to 20 %. Given the additional overheating due to higher voltage harmonics, as well as the deterioration of the cooling conditions when adjusting the rotational speed "down" from the nominal, it seems very relevant

Combined Linkage and Association Analyses of the 124-bp Allele of Marker D2S2944 with Anxiety, Depression, Neuroticism and Major Depression

A central issue in psychiatric genetics is whether positive findings replicate. Zubenko et al. (2002b, Mol. Psychiatry 7:460-467) reported an association of the 124-bp allele of D2S2944 with recurrent early-onset major depression for females. We tested for association of this allele to continuous measures of anxiety, depression and neuroticism in a Dutch sample of 347 males and 448 females, and to DSM-IV major depression in a subsample of 210 males and 295 females. The association of the 124-bp allele to depression in females was not replicated, but there were significant associations (not significant after correction for multiple testing) with anxiety and anxious depression in males. However, the association occurred in the absence of evidence for linkage in this region on chromosome 2. © 2006 Springer Science+Business Media, Inc

Факторы риска при трансплантации печени от посмертного донора: опыт одного центра

Deceased brain-dead donor liver transplantation (LT) is a high-risk intervention. The outcome depends on a large number of modifiable and non-modifiable factors. Objective: to analyze our own experience and identify preoperative and perioperative prognostic factors for poor outcomes in LT. Materials and methods. The study included 301 liver transplants performed between January 2016 and December 2021. Donor and recipient characteristics, intraoperative data, perioperative characteristics including laboratory test data, and the nature and frequency of complications were used for the analysis. Results. The 1-, 3- and 5-year recipient survival rates were 91.8%, 85.1%, and 77.9%, respectively; graft survival rates were 90.4%, 83.7%, and 76.7%, respectively. The most significant predictors of poor outcome of LT on the recipient side were biliary stents (HR 7.203, p < 0.01), acutely decompensated cirrhosis (HR 2.52, p = 0.02); in the postoperative period, non-surgical infectious complications (HR 4.592, p < 0.01) and number of reoperations (HR 4.063, p < 0.01). Donor creatinine level (HR 1.004, p = 0.01, one factor analysis; HR 1.004, p = 0.016, multivariate analysis) was the only reliable prognostic negative factor. Conclusion. LT taking into account established risk factors will improve surgery outcomes and help personalize the therapy for each patient.Трансплантация печени от донора со смертью головного мозга – вмешательство высокого риска, на результаты которого влияет большое количество модифицируемых и немодифицируемых факторов. Цель: провести анализ собственного опыта и выявить предоперационные и периоперационные прогностические факторы риска неблагоприятного исхода при трансплантации печени. Материалы и методы. В исследование включены трансплантации печени (n = 301), выполненные за период с января 2016-го по декабрь 2021 г. Для анализа использованы характеристики доноров и реципиентов, интраоперационные данные, периоперационные характеристики, включая данные лабораторных тестов, а также характер и частоту осложнений. Результаты. Выживаемость реципиентов составила: 91,8; 85,1 и 77,9% на сроке 1, 3 и 5 лет после операции; выживаемость трансплантатов – 90,4; 83,7 и 76,7% соответственно. Наиболее значимыми предикторами неблагоприятного исхода трансплантации печени со стороны реципиента стали наличие билиарных стентов (HR 7,203, p < 0,01), острая декомпенсация течения цирроза печени (HR 2,52, p = 0,02); в послеоперационном периоде – нехирургические инфекционные осложнения (HR 4,592, p < 0,01) и количество повторных операций (HR 4,063, p < 0,01). Уровень креатинина донора (HR 1,004, p = 0,01 – однофакторный анализ; HR 1,004, p = 0,016 – многофакторный анализ) является единственным достоверным прогностически негативным фактором. Выводы. Выполнение трансплантации печени с учетом установленных факторов риска позволит улучшить результаты операций, а также персонализировать терапию для каждого пациента

Genetic Linkage and Association Analysis for Loneliness in Dutch Twin and Sibling Pairs Points to a Region on Chromosome 12q23–24

We obtained evidence from a large study in Dutch twins (N = 8387) and siblings (N = 2295) that variation in loneliness has a genetic component. The heritability estimate for loneliness, which was assessed as an ordinal trait, was 40% and did not differ between males and females. There were 682 sibling pairs with genotypic (around 400 microsatellite markers) data. We combined phenotypic and genotypic data to carry out a genome scan to localize QTLs for loneliness. One region on chromosome 12q23.3-24.3, showed near suggestive linkage. Genetic association tests within this region revealed significant association (p-value 0.009) with one of the alleles of marker D12S79 and with one of the alleles of neighbouring marker D12S395 (p-value 0.043). We review evidence for linkage in this region for psychiatric disorders and discuss our findings within this context. © 2006 Springer Science+Business Media, Inc

Combinatorial Mismatch Scan (CMS) for loci associated with dementia in the Amish

BACKGROUND: Population heterogeneity may be a significant confounding factor hampering detection and verification of late onset Alzheimer's disease (LOAD) susceptibility genes. The Amish communities located in Indiana and Ohio are relatively isolated populations that may have increased power to detect disease susceptibility genes. METHODS: We recently performed a genome scan of dementia in this population that detected several potential loci. However, analyses of these data are complicated by the highly consanguineous nature of these Amish pedigrees. Therefore we applied the Combinatorial Mismatch Scanning (CMS) method that compares identity by state (IBS) (under the presumption of identity by descent (IBD)) sharing in distantly related individuals from such populations where standard linkage and association analyses are difficult to implement. CMS compares allele sharing between individuals in affected and unaffected groups from founder populations. Comparisons between cases and controls were done using two Fisher's exact tests, one testing for excess in IBS allele frequency and the other testing for excess in IBS genotype frequency for 407 microsatellite markers. RESULTS: In all, 13 dementia cases and 14 normal controls were identified who were not related at least through the grandparental generation. The examination of allele frequencies identified 24 markers (6%) nominally (p ≤ 0.05) associated with dementia; the most interesting (empiric p ≤ 0.005) markers were D3S1262, D5S211, and D19S1165. The examination of genotype frequencies identified 21 markers (5%) nominally (p ≤ 0.05) associated with dementia; the most significant markers were both located on chromosome 5 (D5S1480 and D5S211). Notably, one of these markers (D5S211) demonstrated differences (empiric p ≤ 0.005) under both tests. CONCLUSION: Our results provide the initial groundwork for identifying genes involved in late-onset Alzheimer's disease within the Amish community. Genes identified within this isolated population will likely play a role in a subset of late-onset AD cases across more general populations. Regions highlighted by markers demonstrating suggestive allelic and/or genotypic differences will be the focus of more detailed examination to characterize their involvement in dementia

ТРАНСПЛАНТАЦИЯ ПЕЧЕНИ ОТ ДОНОРОВ СТАРШЕ 60 ЛЕТ

Donor organs shortage leads to extending criteria for deceased liver donation in the whole world.Aim: to compare results of deceased donor liver transplantation (DDLT) depending of donor age over 60 years old.Materials and methods: the study includes 390 DDLT from January 2010 to November 2017. All liver donors separated by age for two groups: I – 60 years and older (n = 26); II – younger than 60 years (n = 364). All donors were standardized by demographic, laboratory fi ndings and inotropic drug requirement. Results: no difference between both groups in severity of ischemia-reperfusion injury, ICU or in-hospital staying (median 2 and 7,5 days respectively) was found. There is also no difference between biliary or vascular complication rate. 5-year actuarial survival rate found no difference between both groups (I: 70%: II: 76%, p = 0,54).Conclusion. Using grafts from donors older than 60 years don’t worsen early and late results of DDLT. Care should be taken to avoid other risk factors (cold ischemia time, warm ischemia time).Дефицит донорских органов во всем мире способствует постепенному расширению донорских критериев для трансплантации.Цель: провести анализ результатов трансплантации печени от доноров 60 лет и старше в сравнении с донорами более молодого возраста.Материалы и методы: в исследование включено 390 трансплантаций печени: группа I – возраст донора 60 и более лет (n = 26); группа II – возраст донора менее 60 лет (n = 364), выполненных за период с 2010-го по ноябрь 2017 г. Доноры обеих групп стандартизованы по демографическим характеристикам, лабораторным показателям, а также объему инотропной поддержки.Результаты: статистически значимых различий тяжести ишемически-реперфузионного повреждения трансплантата, длительности пребывания в отделении реанимации, продолжительности пребывания в стационаре не выявлено.Также не выявлено различий в частоте развития билиарных или сосудистых осложнений. Сравнение 5-летней актуриальной выживаемости не показало достоверной разницы (группа I – 70%; группа II – 76%, р = 0,54).Выводы. По нашему опыту, использование трансплантатов печени от доноров старше 60 лет при условии минимизации факторов риска (холодовая ишемия, вторичная тепловая ишемия) не ухудшает результаты трансплантации печени в раннем и отдаленном сроке и может быть одним из путей увеличения числа трансплантаций печени от посмертного донора. Длительность наблюдения за реципиентами 8 лет

Interaction between CRHR1 and BDNF Genes Increases the Risk of Recurrent Major Depressive Disorder in Chinese Population

BACKGROUND: An important etiological hypothesis about depression is stress has neurotoxic effects that damage the hippocampal cells. Corticotropin-releasing hormone (CRH) regulates brain-derived neurotrophic factor (BDNF) expression through influencing cAMP and Ca2+ signaling pathways during the course. The aim of this study is to examine the single and combined effects of CRH receptor 1 (CRHR1) and BDNF genes in recurrent major depressive disorder (MDD). METHODOLOGY/PRINCIPAL FINDING: The sample consists of 181 patients with recurrent MDD and 186 healthy controls. Whether genetic variations interaction between CRHR1 and BDNF genes might be associated with increased susceptibility to recurrent MDD was studied by using a gene-based association analysis of single-nucleotide polymorphisms (SNPs). CRHR1 gene (rs1876828, rs242939 and rs242941) and BDNF gene (rs6265) were identified in the samples of patients diagnosed with recurrent MDD and matched controls. Allelic association between CRHR1 rs242939 and recurrent MDD was found in our sample (allelic: p = 0.018, genotypic: p = 0.022) with an Odds Ratio 0.454 (95% CI 0.266-0.775). A global test of these four haplotypes showed a significant difference between recurrent MDD group and control group (chi-2 = 13.117, df = 3, P = 0.016. Furthermore, BDNF and CRHR1 interactions were found in the significant 2-locus, gene-gene interaction models (p = 0.05) using a generalized multifactor dimensionality reduction (GMDR) method. CONCLUSION: Our results suggest that an interaction between CRHR1 and BDNF genes constitutes susceptibility to recurrent MDD

Transcriptional Evidence for the Role of Chronic Venlafaxine Treatment in Neurotrophic Signaling and Neuroplasticity Including also Glutatmatergic- and Insulin-Mediated Neuronal Processes.

OBJECTIVES: Venlafaxine (VLX), a serotonine-noradrenaline reuptake inhibitor, is one of the most commonly used antidepressant drugs in clinical practice for the treatment of major depressive disorder (MDD). Despite being more potent than its predecessors, similarly to them, the therapeutical effect of VLX is visible only 3-4 weeks after the beginning of treatment. Furthermore, recent papers show that antidepressants, including also VLX, enhance the motor recovery after stroke even in non depressed persons. In the present, transcriptomic-based study we looked for changes in gene expressions after a long-term VLX administration. METHODS: Osmotic minipumps were implanted subcutaneously into Dark Agouti rats providing a continuous (40 mg/kg/day) VLX delivery for three weeks. Frontal regions of the cerebral cortex were isolated and analyzed using Illumina bead arrays to detect genes showing significant chances in expression. Gene set enrichment analysis was performed to identify specific regulatory networks significantly affected by long term VLX treatment. RESULTS: Chronic VLX administration may have an effect on neurotransmitter release via the regulation of genes involved in vesicular exocytosis and receptor endocytosis (such as Kif proteins, Myo5a, Sv2b, Syn2 or Synj2). Simultaneously, VLX activated the expression of genes involved in neurotrophic signaling (Ntrk2, Ntrk3), glutamatergic transmission (Gria3, Grin2b and Grin2a), neuroplasticity (Camk2g/b, Cd47), synaptogenesis (Epha5a, Gad2) and cognitive processes (Clstn2). Interestingly, VLX increased the expression of genes involved in mitochondrial antioxidant activity (Bcl2 and Prdx1). Additionally, VLX administration also modulated genes related to insulin signaling pathway (Negr1, Ppp3r1, Slc2a4 and Enpp1), a mechanism that has recently been linked to neuroprotection, learning and memory. CONCLUSIONS: Our results strongly suggest that chronic VLX treatment improves functional reorganization and brain plasticity by influencing gene expression in regulatory networks of motor cortical areas. These results are consonant with the synaptic (network) hypothesis of depression and antidepressant-induced motor recovery after stroke

Sequence variations of ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1, CRHR1 and NTRK2: association with major depression and antidepressant response in Mexican-Americans

We studied seven genes that reflect events relevant to antidepressant action at four sequential levels: (1) entry into the brain, (2) binding to monoaminergic transporters, and (3) distal effects at the transcription level, resulting in (4) changes in neurotrophin and neuropeptide receptors. Those genes are ATP-binding cassette subfamily B member 1 (ABCB1), the noradrenaline, dopamine, and serotonin transporters (SLC6A2, SLC6A3 and SLC6A4), cyclic AMP-responsive element binding protein 1 (CREB1), corticotropin-releasing hormone receptor 1 (CRHR1) and neurotrophic tyrosine kinase type 2 receptor (NTRK2). Sequence variability for those genes was obtained in exonic and flanking regions. A total of 56 280 000 bp across were sequenced in 536 unrelated Mexican Americans from Los Angeles (264 controls and 272 major depressive disorder (MDD)). We detected in those individuals 419 single nucleotide polymorphisms (SNPs); the nucleotide diversity was 0.00054±0.0001. Of those, a total of 204 novel SNPs were identified, corresponding to 49% of all previously reported SNPs in those genes: 72 were in untranslated regions, 19 were in coding sequences of which 7 were non-synonymous, 86 were intronic and 27 were in upstream/downstream regions. Several SNPs or haplotypes in ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1 and NTRK2 were associated with MDD, and in ABCB1, SLC6A2 and NTRK2 with antidepressant response. After controlling for age, gender and baseline 21-item Hamilton Depression Rating Scale (HAM-D21) score, as well as correcting for multiple testing, the relative reduction of HAM-D21 score remained significantly associated with two NTRK2-coding SNPs (rs2289657 and rs56142442) and the haplotype CAG at rs2289658 (splice site), rs2289657 and rs2289656. Further studies in larger independent samples will be needed to confirm these associations. Our data indicate that extensive assessment of sequence variability may contribute to increase understanding of disease susceptibility and drug response. Moreover, these results highlight the importance of direct re-sequencing of key candidate genes in ethnic minority groups in order to discover novel genetic variants that cannot be simply inferred from existing databases

Трансплантация печени от посмертного донора 73 лет

Orthotopic liver transplantation is the only way to cure chronic liver failure and certain liver tumors. Deceased donor organs are the prevailing source in most transplantation centers. However, there is an organ shortage because of the increasing number of patients in need of transplantation. Using expanded criteria deceased donors is a routine way to overcome organ shortage. The majority of transplantation centers take older donors depending on the local rules. Successful liver transplantation from 73-year-old deceased donor. Recipient suffered from liver neuroendocrine tumor without signs of extrahepatic spread. Liver function is adequate during 90-day follow-up. Liver transplantation from older deceased donors has good outcome according to world experience. Careful donor-recipient selection is the key to success. The first positive trial in our center enlightens the way for further practice.Расширение критериев изъятия печени при трансплантации от доноров со смертью мозга представляет собой наиболее распространенную практику преодоления дефицита органов для трансплантации. В зависимости от принятых правил большинство центров трансплантации не считают возраст противопоказанием к донорству органов при прочих удовлетворительных параметрах, а правильный подбор пары «донор–реципиент» позволяет получить удовлетворительный результат. Приводится клиническое наблюдение трансплантации печени от донора 73 лет реципиенту с метастазами нейроэндокринной опухоли в печень. Функция трансплантата удовлетворительная в течение 3 месяцев на момент публикации. Положительный исход, обзор опыта большого количества центров трансплантации печени позволяют надеяться на дальнейшее расширение подобной практики