Determination of the Lipophilicity of Some New Derivatives of Thiosemicarbazide and 1,2,4-triazoline-5-thione with Potential Antituberculosis Activity

The chromatographic behavior of newly obtained derivatives of thiosemicarbazide and 1,2,4- triazoline-5-thione was determined. The lipophilicity was confirmed by the use of the Reversed Phase Thin-Layer Chromatography (RP-TLC) method. For both groups of solutes the lipophilicity depended on the substituents. All obtained compounds were tested for their antimycotic activity. The strongest antituberculosis activity was observed for 4-(2-iodophenyl)-1-(pyridine-4-ylacetyl)thiosemicarbazide 4 and 4- phenyl-3-(pyridine-4-ylmethyl)-1,2,4-triazoline-5-thione 27

Analiza czynników wpływających na występowanie depresji

Introduction. Depressions are among the civilization diseases of the 21st century and are disorders in the human psyche. It comes in various age groups and affects children, adolescents, women, men and the elderly. In Poland, over 1.5 million people struggle with depression, and at present, during the Covid-19 pandemic, the incidence has increased to over 3 million.Aim. The aim of the study was to evaluate the factors influencing the occurrence of depression.Material and Methods. The study included 200 people — nurses from treatment and conservative departments. The prevalence of depressive disorders was assessed using the Depression Measurement Questionnaire, which consists of 75 statements — terms referring to the approach to life and everyday life. A self-questionnaire containing questions about the socio-demographic characteristics of the respondents was used as a research tool. The obtained results were analysed statistically.Results. In the case of men, the indicator reached a statistically higher value, i.e. 242.2 points, which means the average level, while for women it amounted to 238.1 points, which means a low level. A low level of the NREAP index was shown by the group of respondents aged 20–30, while a high level was observed among the group of respondents aged 41–50. Nurses with lower education — certified ones showed a low level of the DMQ index, while nurses with higher education with a master’s degree obtained a higher level of the DMQ index. According to the statistical analysis, the low level of the KRP indicator was shown by people working briefly in the profession from 1 to 5 years. People who worked in the profession from 11 to 20 years had a high level of DMQ. Nurses working in the conservative ward showed a low level of the DMQ index, while the index of nurses in the surgical wards remained at the average levels.Conclusions. Sociodemographic factors had a significant impact on the occurrence of depressive disorders in the studied group. The study also confirmed a large influence of professional factors on the occurrence of depression among nurses. The statistical analysis showed a significant relationship between the gender, age of the respondents and the depression measurement index — DMQ. (JNNN 2021;10(3):126–132)Wstęp. Depresje zalicza się do chorób cywilizacyjnych XXI wieku to zaburzenia w psychice człowieka. Występuje w różnych przedziałach wiekowych i dotyczy dzieci, nastolatków, kobiet, mężczyzn oraz osób starszych. W Polsce z problemem depresji boryka się ponad 1,5 miliona ludzi natomiast w chwili obecnej, w czasie pandemii Covid-19 nastąpił wzrost zachorowalności do ponad 3 milionów.Cel. Celem pracy była ocena czynników wpływających na występowanie depresji.Materiał i metody. Badaniem objęto 200 osób — pielęgniarek i pielęgniarzy z oddziałów zabiegowych i zachowawczych. Oceny występowania zaburzeń depresyjnych dokonano za pomocą Kwestionariusza Pomiaru Depresji, który składa się z 75 stwierdzeń — określeń odnoszących się do podejścia do życia oraz codzienności. Jako narzędzie badawcze zastosowano kwestionariusz ankiety własnej zawierające pytania dotyczące charakterystyki socjodemograficznej respondentów. Otrzymane wyniki poddano analizie statystycznej.Wyniki. W przypadku mężczyzn wskaźnik osiągnął statystycznie wyższą wartość, czyli 242,4 punkty co oznacza średni poziom natomiast wśród kobiet wyniósł on 238,1 punktów co oznacza niski poziom. Niski poziom wskaźnika KPD wykazała grupa badanych w przedziale wiekowym 20–30 lat natomiast wysoki wskaźnik wystąpił wśród grupy badanych w wieku 41–50 lat. Pielęgniarki z niższym wykształceniem — dyplomowane wykazały niski poziom wskaźnika KPD natomiast pielęgniarki z wyższym wykształceniem tytułem magistra uzyskały wyższy poziom wskaźnika KPD. Według analizy statystycznej niski poziom wskaźnika KPD wykazały osoby pracujące krótko w zawodzie od 1 do 5 lat. Wysoki poziom wskaźnika KPD miały osoby, które pracowały w zawodzie od 11 do 20 lat. Pielęgniarki pracujące na oddziale zachowawczym wykazały niski poziom wskaźnika KPD natomiast wskaźnik pielęgniarek na oddziałach zabiegowych utrzymywał się na poziomie średnim.Wnioski. Czynniki socjodemograficzne miały istotny wpływ na występowanie zaburzeń depresyjnych w badanej grupie. Badanie potwierdziło również duży wpływ czynników zawodowych na występowanie depresji wśród pielęgniarek. Analiza statystyczna wykazała istotną zależność pomiędzy płcią, wiekiem ankietowanych a wskaźnikiem pomiaru depresji — KPD. (PNN 2021;10(3):126–132

The effect of storage on the yogurt fatty acid profile

U ovom istraživanju je ispitivan utjecaj hladnog skladištenja na profil masnih kiselina, sadržaj konjugirane linolne kiseline (CLA) te trans izomera masnih kiselina C18:1 i C18:2 u jogurtima od kravljeg, kozjeg i ovčjeg mlijeka. Na 21. dan skladištenja utvrđen je značajan pad (P<0,05) sadržaja jednostruko (MUFA) i višestruko nezasićenih (PUFA) masnih kiselina u jogurtima od kravljeg mlijeka. Sadržaj ovih masnih kiselina mijenjao se u jogurtima od ovčjeg i kozjeg mlijeka. Sadržaj izomera CLA u svježe pripremljenim jogurtima kretao se između 3,58 mg g-1 masti (ovčji jogurt) i 4,47 mg g-1 masti (kravlji jogurt). Tijekom perioda skladištenja se sadržaj CLA značajno snizio u kravljem jogurtu, dok je značajno narastao u kozjem jogurtu (P<0.05), a u ovčjem jogurtu je ostao više manje nepromijenjen.The presented study analysed whether refrigerated storage time affects the fatty acid profile, the content of conjugated linoleic acid (CLA) and trans isomers of C18:1 and C18:2 acids in yogurts made from goat, sheep and cow milk. On the 21st day of storage, significant decreases (P<0.05) in monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) were observed in in yogurts made from cow milk. In yogurts made from sheep and goat milk, the content of these acids fluctuated during storage. The CLA isomer in fresh yogurts ranged from 3.58 mg g-1 fat in yogurts made from sheep milk to 4.47 mg g-1 fat in yogurts made of cow milk. During storage the content of CLA significantly decreased in cow milk yogurts and significantly increased in goat milk yogurts (P<0.05), while it remained more or less unchanged throughout the entire storage period in sheep milk yogurts

Demographic and economic correlates of mortality due to traffic accidents among children aged 114 years in European countries

Background: To evaluate the changes of mortality among children aged 1-14 yr due to road traffic injury and related demographic and economic factors in an ecological study undertaken in 33 European countries. Methods: Information about mortality due to road traffic injury among children aged 1-14 yr in European countries was obtained from the WHO database. Changes in the mortality for the years 2000-2009 were estimated as linear regression. These deaths were correlated with demographic and economic factors. Results: The greatest burden of child mortality due to road traffic accidents was observed in Baltic States, three times lower mortality levels than that in Northern States. Between 2000 and 2009, there was a significant reduction (P<0.05) in mortality among children aged 1-14 yr in Southern-West countries and Western countries, 1-4 yr in Central and Eastern countries, and 5-14 yr in Northern countries. Mortality due to road traffic injury among boys was strongly associated with the level of urbanization. Both sexes showed strong negative correlations with the economic level and strong positive correlations with income inequality. Conclusion: Although in European countries the mortality of children due to traffic injury was considerably reduced, efforts should be made to educate and design a safe environment

Determination of the Lipophilicity of Some New Derivatives of Thiosemicarbazide and 1,2,4-triazoline-5-thione with Potential Antituberculosis Activity

The chromatographic behavior of newly obtained derivatives of thiosemicarbazide and 1,2,4- triazoline-5-thione was determined. The lipophilicity was confirmed by the use of the Reversed Phase Thin-Layer Chromatography (RP-TLC) method. For both groups of solutes the lipophilicity depended on the substituents. All obtained compounds were tested for their antimycotic activity. The strongest antituberculosis activity was observed for 4-(2-iodophenyl)-1-(pyridine-4-ylacetyl)thiosemicarbazide 4 and 4- phenyl-3-(pyridine-4-ylmethyl)-1,2,4-triazoline-5-thione 27

A nonspecific clinical picture and the course of Conn syndrome — current findings in the screening program for hypertensive patients

Conn syndrome (CS), next to bilateral adrenal hyperplasia, is one of the most common causes of primary hyperaldosteronism. It leads to potentially curable secondary hypertension. The 54-year-old woman underwent an abdominal computed tomography (CT) examination for symptomatic nephrolithiasis. A focal lesion of the left adrenal gland was found with a diameter of 16 mm and a density of 34 Hounsfield units (HU). The lesion was under observation, and the next magnetic resonance imaging (MRI) scans showed a slight enlargement of the lesion to a size of 18 x 12 mm. The lesion was interpreted as an atypical adenoma of the adrenal gland. According to the course, the patient was referred to the endocrinology clinic. The patient's symptoms included hypertension and paresthesia. During two separate hospitalizations, Conn syndrome was diagnosed using a specific laboratory test. The patient was successfully treated by surgical intervention, resulting in remission of all symptoms. This case illustrates the difficulties in diagnosing primary hyperaldosteronism. The symptoms of Conn syndrome may vary in severity or may be absent. Early diagnosis and appropriate treatment can save many ill individuals from cardiovascular, metabolic, or renal complications. The case underscores the need for screening hypertensive patients using the aldosterone-renin ratio (ARR)

Model of the distribution of diastolic left ventricular posterior wall thickness in healthy adults and its impact on the behavior of a string of virtual cardiomyocytes

Correlation of the thickness of the left ventricular posterior wall (LVPWd) with various parameters, including age, gender, weight and height, was investigated in this study using regression models. Multicenter derived database comprised over 4,000 healthy individuals. The developed models were further utilized in the in vitro-in vivo (IVIV) translation of the drug cardiac safety data with use of the mathematical model of human cardiomyocytes operating at the virtual healthy population level. LVPWd was assumed to be equivalent to the length of one-dimensional string of virtual cardiomyocyte cells which was presented, as other physiological factors, to be a parameter influencing the simulated pseudo-ECG (pseudoelectrocardiogram), QTcF and $\Delta$QTcF, both native and modified by exemplar drug (disopyramide) after $I_{Kr}$ current disruption. Simulation results support positive correlation between the LVPWd and QTcF/$\Delta$QTc. Developed models allow more detailed description of the virtual population and thus inter-individual variability influence on the drug cardiac safet

SYK inhibition targets acute myeloid leukemia stem cells by blocking their oxidative metabolism

Spleen tyrosine kinase (SYK) is an important oncogene and signaling mediator activated by cell surface receptors crucial for acute myeloid leukemia (AML) maintenance and progression. Genetic or pharmacologic inhibition of SYK in AML cells leads to increased differentiation, reduced proliferation, and cellular apoptosis. Herein, we addressed the consequences of SYK inhibition to leukemia stem-cell (LSC) function and assessed SYK-associated pathways in AML cell biology. Using gain-of-function MEK kinase mutant and constitutively active STAT5A, we demonstrate that R406, the active metabolite of a small-molecule SYK inhibitor fostamatinib, induces differentiation and blocks clonogenic potential of AML cells through the MEK/ERK1/2 pathway and STAT5A transcription factor, respectively. Pharmacological inhibition of SYK with R406 reduced LSC compartment defined as CD34+CD38-CD123+ and CD34+CD38-CD25+ in vitro, and decreased viability of LSCs identified by a low abundance of reactive oxygen species. Primary leukemic blasts treated ex vivo with R406 exhibited lower engraftment potential when xenotransplanted to immunodeficient NSG/J mice. Mechanistically, these effects are mediated by disturbed mitochondrial biogenesis and suppression of oxidative metabolism (OXPHOS) in LSCs. These mechanisms appear to be partially dependent on inhibition of STAT5 and its target gene MYC, a well-defined inducer of mitochondrial biogenesis. In addition, inhibition of SYK increases the sensitivity of LSCs to cytarabine (AraC), a standard of AML induction therapy. Taken together, our findings indicate that SYK fosters OXPHOS and participates in metabolic reprogramming of AML LSCs in a mechanism that at least partially involves STAT5, and that SYK inhibition targets LSCs in AML. Since active SYK is expressed in a majority of AML patients and confers inferior prognosis, the combination of SYK inhibitors with standard chemotherapeutics such as AraC constitutes a new therapeutic modality that should be evaluated in future clinical trials

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention