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The chemical instability of the survivin inhibitor – sepantronium bromide (YM155) studied by Stimulated Raman, NMR and UV-Vis spectroscopies
No full textSepantronium bromide, which shows a broad spectrum of anticancer action, is allegedly chemically unstable. This instability might significantly limit the final antineoplastic efficacy of the drug. Here, we report our studies on these chemical stability issues under different chemical environments using advanced spectroscopies. With UV-Vis spectroscopy, we observed a degradation product which absorbs around 450 nm. The degradation accelerated strongly at alkaline pH (>8.5) and in the presence of a buffer, particularly PBS. We performed NMR and stimulated Raman studies to identify the degradation product and analysed the degradation kinetics. With both methods, we observed H→D isotope exchange at the methyl group linked to the imidazole group of YM155, after dissolving YM155 in D2O. The exchange was similarly both alkaline- and buffer-catalysed. We were unable to identify the 450 nm-absorbing product of the degradation neither by NMR nor stimulated Raman, yet our studies pointed at imidazole-linked methyl as being associated with the YM155 degradation. The alkaline degradation of YM155 could be related to its mechanism of action – binding to DNA in mitochondria with pH values above 8.Polish National Science Centre (NCN) under research project no. UMO-2021/43/I/ST4/01411. M.P and S.S. were supported by by the TEAM-NET program of the Foundation for Polish Science, co-financed by the European Union under the European Regional Development Fund (Grant No. POIR.04.04.00-00-16ED/18-00)
Correlation of serum vitamin B12, folate, and magnesium levels with severity of fibrosis in non-alcoholic fatty liver disease in the medical ICU
No full textINTRODUCTION: Non-Alcoholic Fatty Liver Disease (NAFLD) has emerged as a major public health concern worldwide. Characterised by the accumulation of fat in liver cells in the absence of significant alcohol consumption, NAFLD spans a spectrum of conditions, from simple steatosis to more severe forms such as non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and liver cancer. Recent research has also highlighted the critical role of micronutrients in the development and management of NAFLD, suggesting that deficiencies or imbalances in essential vitamins and minerals may influence disease progression and response to treatment. Therefore, the objective of the study was to evaluate the correlation of serum vitamin B12, folate, and magnesium levels with the severity of fibrosis in non-alcoholic fatty liver disease in the medical ICU. MATERIALS AND METHODS: A prospective cross-sectional observational study was evaluated involving 70 patients with NAFLD diagnosis based on history, ultrasound abdomen and fulfilling inclusion criteria during the study period. The severity of liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) was evaluated using the NAFLD Fibrosis Score. RESULTS: Patients with low vitamin B12 had a mean fibrosis score of 0.46 (SD 1.59), compared to -1.05 (SD 1.43) for those with normal Vitamin B12 levels, with a p-value of 0.009, indicating a significant difference. Patients with low folate levels had a mean fibrosis score of -0.36 (SD 1.63), while those with normal folate levels had a mean score of -1.19 (SD 1.40), with a p-value of 1x10-6. Patients with low magnesium levels had a mean fibrosis score of -0.3 (SD 1.6), while those with normal levels had a score of -1.28 (SD 1.38) (p = 0.001), suggesting a significant difference. CONCLUSIONS: The study concluded that serum levels of Vitamin B12, folate, and magnesium are all correlated with the severity of fibrosis in patients with NAFLD, with folate showing the strongest association. Folate had a significant negative correlation of -0.45 with fibrosis scores, compared to -0.34 for Vitamin B12 and -0.31 for magnesium
Multifaced lipoedema: a problematic and complex condition in the population of young women
No full textLipoedema is a chronic disease with various manifestation of symptoms, related to excessive deposition of subcutaneous adipose tissue in the legs, hips and buttocks. The scale of the problem is enormous and may affect up to one in five women. Lipoedema is often underdiagnosed and misdiagnosed with lymphedema, obesity or lipohypertrophy. In recent years, lipedema has been diagnosed in an increasing number of younger women, and its first symptoms may manifest already in puberty. Even though it is often perceived as only an aesthetic problem, it has a huge impact on the quality of life, mental health, self-esteem or self-confidence. Moreover, lipoedema causes stigmatization, unfortunately also in healthcare professionals. Nevertheless, recently, diagnostic criteria (also ultrasound) have been created, and lipedema has been classified in ICD-10 (E88.2). There are also more and more treatment options, with emphasis on the role of psychological care. Awareness and knowledge of lipoedema have also increased despite its underestimation but still is not enough. The multidimensional nature of lipoedema and its impact on many aspects of life highlights the essential role of comprehensive support to patients. Nowadays, in times of caring for mental health, it is crucial to increase public awareness and spread knowledge about lipoedema
Shedding new light on quadrupolar 1,4-dihydropyrrolo[3,2-b]pyrroles: impact of electron-deficient scaffolds over emission
Get PDFIn this work, we disclose a series of seven quadrupolar centrosymmetric 1,4-dihydropyrrolo[3,2-b]pyrroles (DHPPs) linked to the two peripheral, strongly electron-accepting heterocycles such as benzoxadiazole, benzothiadiazole and benzoselenadiazole. This represents the first study probing the influence of electron-deficient heterocycles, rather that small electron-withdrawing substituents, on photophysics of DHPPs. These new acceptor–donor–acceptor hybrid dyes exhibit an appreciable combination of photophysical properties including absorption maxima in the range of 470–620 nm, and emission in the range of 500–720 nm with fluorescence quantum yields reaching 0.88. We discovered that the presence of two 7-nitro-benzoxadiazolyl substituents at positions 2 and 5 of DHPP core, evokes a strong fluorescence in non-polar solvents shifted to 639 nm. This is the most bathochromically shifted emission for quadrupolar, centrosymmetric chromophore bearing exclusively biaryl linkages. Interestingly, 1,2,4,5-tetraaryl-1,4-dihydropyrrolo[3,2-b]pyrrole (TAPP) possessing 4-benzothiadiazolyl groups is strongly emitting in the crystalline state (fluorescence quantum yield = 0.43). The combined photophysical and crystallographic studies point towards existence of intermolecular hydrogen bonds which modify the dihedral angles between the donor and acceptor moieties as a primary reason for this strong emission. Small structural alteration via the replacement of two 2,1,3-benzoxadiazole scaffolds with 2,1,3-benzoxadiazole-2-oxide moieties causes >103 decrease in the fluorescence intensity. Computational studies point out to strong charge transfer originating from exceptionally large dihedral angles as the pivotal reason of this phenomenon. Although internal conversion originating from the charge-transfer state is the prevailing non-radiative deactivation mechanism, intersystem crossing also plays a role. The rational design of DHPPs that enables modulation of emission will advance their applicability.National Science Centre in Poland (OPUS 2020/37/B/ST4/00017 and HARMONIA 2018/30/M/ST5/00460 grants);
European Union's Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie grant agreement no. 101007804;
National Academic Infrastructure for Super Computing in Sweden (NAISS, 2023/5-77) at the National Supercomputer Centre (NSC) at Linköping University partially funded by the Swedish Research Council through grant agreement no. 2022-06725;
Swedish Research Council (no. 2020-04600);
Swedish Government Strategic Research Area in Materials Science on Advanced Functional Materials at Linköping University (Faculty grant SFO-Mat-LiU no. 2009-00971);
European Union (ERC, LUMOR, 101077649);
Olle Engkvist Byggmastare Foundation (contract no. 212-0136);
European Union within the European Regional Development Fund (program no. POIG.02.01.00-14.122/09)
Sposób wytwarzania kształtek dla systemów instalacji do gorącej i zimnej wody
Get PDFDane do uzyskanych wyników prac B+R w ramach Projektu pn:
„Prace B+R oraz rozwój dotychczasowego zaplecza B+R w DETAL-MET Sp. z o.o. celem zbadania, opracowania i wdrożenia innowacyjnych metod i parametrów wtrysku tworzyw sztucznych w technologii z wykorzystaniem gazu”.
Dane dotyczące wniosku o udzielenie patentu na wynalazek pn.: „Sposób wytwarzania kształtek dla systemów instalacji do gorącej i zimnej wody”.Sposób wytwarzania kształtek dla systemów instalacji do gorącej i zimnej wody, w którym tworzywo sztuczne jest uplastyczniane i wtryskiwane do formy, a następnie wydobywane z formy i poddawane chłodzeniu, polega na tym, że do tworzywa sztucznego dodaje się 10-15% gazu obojętnego. Gaz obojętny dozuje się na etapie uplastyczniania tworzywa sztucznego. Jako tworzywo sztuczne stosuje się randomiczny kopolimer polipropylenu. Jako gazu obojętnego używa się azotu. Tworzywo sztuczne uplastycznia się w temperaturze 170-215 stopni Celsjusza i wtryskuje do formy o temperaturze 24-40 stopni Celsjusza z prędkością 16,8-35 mm/s pod ciśnieniem 550-1050 barów i ciśnieniem docisku wynoszącym na początku procesu 200-600 barów i spadającym do 50 barów. Siła zwarcia w trakcie wtryskiwania wynosi 800-1100 kN, czas docisku wynosi 2 sekundy, a czas chłodzenia wynosi 80-500 sekund.DETAL-MET Sp. z o.o
The Elite Among Users: Identity Formation of Vendors and Customers on Darknet Drug Trade Sites
Get PDFThe present research was supported by the Polish National Science Centre (Narodowe Centrum Nauki) grant 2021/43/B/HS6/00710
Aviation law from the perspective of safety and sustainable development
No full textGłównym celem monografii jest przedstawienie podstawowych zasad funkcjonowania prawa lotniczego oraz wyzwań związanych z jego adaptacją do szybko zmieniającej się rzeczywistości technologicznej i politycznej. Analizie poddane zostały przepisy międzynarodowe, takie jak konwencje i umowy regulujące międzynarodowy transport lotniczy, a także krajowe regulacje, które implementują te międzynarodowe standardy. Publikacja dotyczy także kluczowych kwestii praktycznych, takich jak odpowiedzialność przewoźników lotniczych, prawo do odszkodowań za opóźnienia i odwołania lotów, zasady ochrony pasażerów oraz zmiany w prawie lotniczym związane z nowymi formami transportu, jak drony czy eVTOL. Celem monografii jest nie tylko przedstawienie teoretycznych podstaw prawa lotniczego, ale także ukazanie jego zastosowania w praktyce oraz wpływu na rozwój branży lotniczej i regulacje w skali globalnejThe main purpose of the monograph is to present the basic principles of aviation law and the challenges of its adaptation to rapidly changing technological and political realities. International regulations, such as conventions and agreements regulating international air transport, as well as national regulations that implement these international standards, are analyzed. The publication also addresses key practical issues, such as the liability of air carriers, the right to compensation for flight delays and cancellations, the principles of passenger protection, and changes in aviation law related to new forms of transportation, such as drones and eVTOL. The purpose of the monograph is not only to present the theoretical foundations of aviation law, but also to show its application in practice and its impact on the development of the aviation industry and regulation on a global scale
Zarządzanie czasem w erze pracy zdalnej
Get PDFCelem artykułu jest systematyzacja wiedzy na temat zarządzania czasem w kontekście pracy zdalnej, która zyskała na znaczeniu zwłaszcza po wybuchu pandemii COVID-19. Praca opiera się na przeglądzie literatury oraz wynikach wybranych badań empirycznych, ukazujących, jak praca zdalna wpływa na efektywność, organizację dnia pracy, koncentrację oraz równowagę między życiem zawodowym a prywatnym. W artykule omówiono kluczowe koncepcje teoretyczne i techniki zarządzania czasem, takie jak metoda Pomodoro, macierz Eisenhowera, planowanie blokowe czy podejście oparte na głębokiej pracy (deep work). Autorzy wskazują także na znaczenie samoregulacji i roli organizacji w tworzeniu środowiska wspierającego produktywność zdalną. Wnioski zawarte w artykule podkreślają konieczność wypracowania zrównoważonego i elastycznego podejścia do pracy, które uwzględnia zarówno potrzeby pracowników, jak i cele organizacyjne
Scrub typhus complicating hemophagocytic lymphohistiocytosis: a case report
Get PDFHemophagocytic lymphohistiocytosis (HLH) is a rare disorder characterised by uncontrolled activation of CD8+ T lymphocytes and macrophages, resulting in organ damage. While primary HLH is associated with genetic defects, secondary HLH can be triggered by infections, malignancies, or autoimmune disorders. Scrub typhus-induced HLH underscores the importance of considering tropical fevers as potential triggers for HLH. We present the case of a 27- year-old man who was admitted with no known comorbidities, who had multiple complaints of loose stool for the past 10 days,, fever for the past 8 days and dry cough for the past 3 days. The initial investigation showed bicytopenia, transaminitis, and hyponatremia. A tropical fever study was done, which was negative for typhoid fever, dengue, malaria, HIV, and viral hepatitis. Scrub IgM turned out to be positive. EBV IgM was negative, and Leptospira IgM was negative. The patient was treated with IV antibiotic doxycycline. Since the patient's counts did not improve and had a daily fever spike despite being on antibiotic. On the basis of the H score, the probability of HLH came out. Due to high suspicion of HLH, pulse steroids (1 g of methylprednisolone for 3 days) were started and monitored for counts and fever spikes, which settled after the course of steroids. At follow-up, the patient had no episodes of fever, and the bicytopenia resolved. Early recognition and intervention are crucial for reducing mortality in HLH. This case report contributes to pathophysiology, diagnosis and management the understanding of HLH, highlighting the need for vigilance in patients presenting with scrub typhus and associated complications
Artificial intelligence as a tool for addressing racial and socioeconomic inequalities in cardiac arrest: a systematic review.
Get PDFINTRODUCTION: To determine whether artificial intelligence (AI) interventions have the potential to mitigate racial and socioeconomic disparities in out-of-hospital cardiac arrests (OHCA).OHCA remains a leading cause of mortality globally, with survival rates significantly influenced by systemic healthcare inequalities. Research has identified significant disparities in OHCAs, ethnic minorities have double the risk of OHCA mortality in comparison to Caucasians, and this data has not changed in over 30 years. The AI revolution has captivated physicians with its ability to improve outcomes. The question now pivots to whether it can ameliorate disparities which have been ever present in medical history. This study aims to explore the role of AI in identifying these disparities in the context of OHCA focused on potential benefits and limitations of AI when applied. MATERIALS AND METHODS: A systematic search was conducted in CINAHL and Medline databases, restricted to studies published in the last five years. The search found 164 papers, narrowed to 20 after applying inclusion and exclusion criteria. Seven studies were identified as relevant to the question, focused on AI’s role in addressing disparities in OHCA outcomes. RESULTS: Two overarching themes were identified to encapsulate current research that can be utilised to promote awareness and mitigate ensuring disparities in OHCAs: racial and socioeconomic disparities identified by AI, and implications of AI interventions in OHCA. AI demonstrates the capacity to identify disparities through geographic and demographic predictors but is limited in its ability due to gaps in implementation and ethical programming practices. CONCLUSIONS: The intersectionality of high-risk socioeconomic status and ethnic group minorities in OHCA prevalence is evident, where low-income black sociodemographic contend with incomparable vulnerability. AI presents many opportunities for emergency medicine. However, at present AI should not be implemented as it would only widen disparities and not mitigate due to a lack of relational ethics in the programming process and evolving AI research failing to acknowledge race and socioeconomic characteristics as influential variables on OHCA outcomes
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