Piperazinylpyrimidine analogues as protein kinase inhibitors

The invention provides novel compounds based on piperazinylpyrimidine derivatives to be used as protein kinase inhibitors. The compounds may be useful in treating or preventing different cellular proliferation disorders, such as cancer. The present invention also provides methods of preparing these compounds, and methods of using the same

Consumption of private goods as substitutes for environmental goods in an economic growth model

We analyze growth dynamics in an economy where a private good can be consumed as a substitute for a free access environmental good. In this context we show that environmental deterioration may be an engine of economic growth. To protect themselves against environmental deterioration, economic agents are forced to increase their labour supply to increase the production and consumption of the private good. This, in turn, further depletes the environmental good, leading economic agents to further increase their labour supply and private consumption and so on. This substitution process may give rise to self-enforcing growth dynamics characterized by a lack of correlation between capital accumulation and private consumption levels, on one side, and economic agents’ welfare, on the other. Furthermore, we show that agents’ self-protection consumption choices can generate indeterminacy; that is, they can give rise to the existence of a continuum of (Nash) equilibrium orbits leading to the same attracting fixed point or periodic orbit

Pharmacological Inhibition of CDK8 in Triple-Negative Breast Cancer Cell line MDA-MB-468 Increases E2F1 Protein, Induces Phosphorylation of STAT3 and Apoptosis

Cyclin-dependent kinase 8 (CDK8) has been identified as a colon cancer oncogene. Since this initial observation, CDK8 has been implicated as a potential driver of other cancers including acute myelogenous leukemia (AML) and some breast cancers. Here, we observed different biological responses to CDK8 inhibition among colon cancer cell lines and the triple-negative breast cancer (TNBC) cell line MDA-MB-468. When treated with CDK8 inhibitor 4, all treated cell lines responded with decreased cell viability and increased apoptosis. In the MDA-MB-468 cell line, the decrease in cell viability was dependent on increased phosphorylation of signal transducer and activator of transcription 3 (STAT3), which is not observed in the colon cancer cell lines. Furthermore, increased STAT3 phosphorylation in 4 treated MDA-MB-468 cells was dependent on increased transcription factor E2F1 protein. These results are consistent with previous reports of exogenous expression of E2F1-induced apoptosis in MDA-MB-468 cells

Submucosal lipoma of the cecum

Catedra de chirurgie nr. 1 „Nicolae Anestiadi”, Laboratorul de chirurgie hepato-pancreato-biliară, Catedra de morfopatologie, USMF „Nicolae Testemițanu”, IMSP Spitalul Republican al ACSR, Chișinău, Republica Moldova, Conferința stiințifică „Nicolae Anestiadi – nume etern al chirurgiei basarabene” consacrată centenarului de la nașterea profesorului Nicolae Anestiadi 26 august 2016Introducere. Lipomul colonului este o tumoare benignă relativ rară. Prezentă un caz clinic de lipom cecal gigant complicat cu multiple episoade de ocluzie intestinală. Material şi metodă. O pacientă de 51 ani a fost internată pentru durere abdominală cu localizare în flancul drept, alternantă cu diaree şi constipaţie. Semnele clinice au persistat timp de 3 luni. Irigografia cu dublu contrast a pus în evidenţă o tumoare polipoidă de aprox. 7 cm în diametru, care obtura lumenul cecului şi colonul ascendent. Colonoscopia a pus în evidenţă o tumoare submucoasă probabil benignă, însă prea mare pentru a putea fi rezecată endoscopic. Intraoperator a fost observată o tumoră dură, masivă a colonului drept, care a indus invaginare colo-colonică. A fost practicată hemicolonectomie dreaptă, iar examenul histopatologic a confirmat lipom submucos al cecului. Rezultate. Timp de şase ani postoperator pacientul nu a mai prezentat nici unul din semnele clinice anterioare. Concluzie. Este prezentată revista literaturii, incidenţa, diagnosticul şi tratamentul lipomelor colonului.Introduction. Lipoma of the colon is a relatively rare benign tumor. A case with intermittent subacute colon obstruction due to a giant lipoma of the cecum is reported. Material & methods. A 51-year-old woman presented with intermittent, abdominal crampy pain in the right upper and lower quadrants, accompanied by alternative episodes of diarrhea and constipation. She had had similar symptoms over the last three months. A double-contrast barium enema showed a large (approx. 7 cm in diameter) polypoid mass occluding the lumen of the cecum and the ascending colon. Colonoscopy revealed a submucosal mass suspected of benign tumor but too large for endoscopic resection. Surgery revealed a hard elongated mass in the right colon, which telescoped into the transverse colon and caused colo-colonic intussusception. Right hemicolectomy was performed and pathology documented a mature, submucosal lipoma of the cecum. Results. Six years after the surgery, the patient has not showed any of the previous symptoms. Conclusion. Along with a review of the literature, the incidence, diagnosis complications and treatment of colonic lipomas are discussed

Bayesian sequential integration within a preclinical pharmacokinetic and pharmacodynamic modeling framework:Lessons learned

The present manuscript aims to discuss the implications of sequential knowledge integration of small preclinical trials in a Bayesian pharmacokinetic and pharmacodynamic (PK-PD) framework. While, at first sight, a Bayesian PK-PD framework seems to be a natural framework to allow for sequential knowledge integration, the scope of this paper is to highlight some often-overlooked challenges while at the same time providing some guidances in the many and overwhelming choices that need to be made. Challenges as well as opportunities will be discussed that are related to the impact of (1) the prior specification, (2) the choice of random effects, (3) the type of sequential integration method. In addition, it will be shown how the success of a sequential integration strategy is highly dependent on a carefully chosen experimental design when small trials are analyzed

Режимы пропитки сортиментов из древесины сосны маслянистыми антисептиками

Исследованы технологические свойства масляных пропиток, применяемых при изготовлении шпал и столбов линий электропередач из древесины мягких лиственных пород. Цель – оптимизация параметров модифицирования древесины при производстве железнодорожных шпал и столбов линий электропередач для увеличения срока их службы. Анализируемый фактор – глубина поглощения поперек волокон. Использована лабораторная пропиточная установка с автоклавом, рабочее давление которого – до 20 атм. Маслянистый антисептик объемом 10 л нагревается трубчатыми электронагревателями до температуры 110 °С. Установка по своему назначению эквивалентна работе автоклава в цехе пропитки древесины. При разных режимах было пропитано 25 образцов шпал и 25 образцов столбов линий электропередач. Длительность процесса составляет от 2 до 4 ч. Нормированное содержание антисептика 19 % обеспечивается давлением 10–14 атм при продолжительности выдержки образцов 60 мин. Прогрев заготовки оказался наиболее влияющим на глубину поглощения фактором – как для шпал, так и для столбов. Показано, что нормальная глубина пропитки в случае применения в качестве антисептика каменноугольного масла достигается при температуре древесины не менее 70 °С, поскольку вязкость снижается в 2 раза. Для поглотительного масла такой зависимости не наблюдается, его вязкость мало зависит от температуры. Данную температуру следует рекомендовать для поглотительного и сланцевого масел, т. к. для предотвращения растрескивания древесины минимально допустимый перепад между температурой пропитывающего вещества (110 °С) и температурой древесины (70 °С) не должен превышать 40 °С. Из 6 антисептиков рекомендуемые для применения – каменноугольное, поглотительное, «Шубарколь комир» и антраценовое масла. Для них разработаны режимы пропитки шпал и опор линий электропередач. При выдержке заготовок шпал и столбов в вакууме с разрежением 0,2 атм в течение 40 мин полностью исключается вытекание масла из заготовок после окончания пропитки. Для цитирования: Шамаев В.А., Медведев И.Н., Руссу А.В. Режимы пропитки сортиментов из древесины сосны маслянистыми антисептиками // Изв. вузов. Лесн. журн. 2023. № 6. С. 136–148. https://doi.org/10.37482/0536-1036-2023-6-136-14

Epidemiology of osteoporotic fracture in Moldova and development of a country-specific FRAX model

Summary Retrospective population-based survey in 2 regions of the Republic of Moldova determined the incidence of fractures at the hip, proximal humerus and distal forearm. The estimated number of such fractures nationwide for 2015 was 11,271 and is predicted to increase to 15,863 in 2050. The hip fracture rates were used to create a FRAX model to help guide decisions about treatment. Objective This paper describes the epidemiology of osteoporotic fractures in Republic of Moldova that was used to develop the country-specific fracture prediction FRAX® tool. Methods We carried out a retrospective population-based survey in 2 regions of the Republic of Moldova (Anenii Noi district and Orhei district) representing approximately 6% of the country’s population. We identified hip, forearm and humerus fractures in 2011 and 2012 from hospital registers and primary care sources. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Moldova. Fracture probabilities were compared with those from neighbouring countries having FRAX models. Results The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 3911 and is predicted to increase by 60% to 6492 in 2050. Hip fracture incidence was a good predictor of forearm and humeral fractures. FRAX-based probabilities were higher in Moldova than neighbouring countries (Ukraine and Romania). Conclusion The FRAX model should enhance accuracy of determining fracture probability among the Moldavan population and help guide decisions about treatment