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Minimum expectations for market authorization of continuous glucose monitoring devices in Europe—‘eCGM’ compliance status
Get PDFThe role of focal adhesion kinase in bladder cancer
Get PDFBackground: Focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase, plays a crucial role in focal adhesion turnover by interfacing between the extracellular space, transmembrane integrins, and actin filaments. Its significance for the progression of several malignancies, including bladder cancer, has been well-documented. However, its precise role and the implications of its inhibition in bladder cancer tissues and urothelial in vitro models has not been fully explored. This study examined FAK expression and function in human bladder cancer biopsies and in vitro bladder cancer models. Materials and methods: Ex vivo analyses were performed using reverse transcription-quantitative PCR (qRT-PCR), western blotting, and immunohistochemistry to compare FAK expression between bladder cancer tissues and adjacent normal tissues. In vitro, FAK expression was assessed in low-grade (LG) human non-invasive papilloma urothelial cell line RT4 for NMIBC (Ta), high-grade (HG) human muscle-invasive cancer urothelial cell line T24 for MIBC (T2) and normal porcine urothelial (NPU) cells using qRT-PCR and western blotting, as well as flow cytometry for the quantification of FAK-positive RT4 and T24 cells. The role of FAK in cancer cell survival was explored in vitro using microRNA (miRNA) to silence FAK expression. Additionally, we used FAK inhibitors PND-1186, PF-573228 and defactinib to investigate the effects of FAK inhibition on normal compared to cancerous bladder urothelial cells. Results: Ex vivo analyses demonstrated significantly higher FAK expression in bladder cancer tissues compared to adjacent normal tissues. Similarly, in vitro analyses showed significantly higher FAK expression in RT4 and T24 cells than NPU cells. Silencing FAK using anti-FAK plasmids led to increased caspase-3-mediated apoptosis of RT4 and T24 cells and growth reduction of stably transfected T24 cells. Importantly, based on cell viability assays, treatment with 100 μM defactinib for 2 hours per day on 3 consecutive days was identified as a clinically relevant regimen. Under this treatment, the viability of differentiated NPU cells remained high at 108.4 ± 17.1%, while the viability of 2-day RT4 and 2-day T24 cells was drastically reduced to 4.1 ± 2.7% and 7.6 ± 2.9%, respectively. Conclusions: To our knowledge, this is the first report demonstrating the role of FAK and its inhibition across both normal and cancerous bladder urothelial models. This study highlights the critical role of FAK in the progression of human bladder cancer and establishes a foundation for exploring FAK inhibition as a potential therapeutic approach in bladder cancer treatment
Inovacije in izzivi mobilizacije lesa – mednarodni študijski dnevi projekta FOREST4EU v Sloveniji
Get PDFEthical considerations and multidisciplinary care for pediatric patients with hypoplastic left heart syndrome
Get PDFBackground: Hypoplastic left heart syndrome (HLHS) was a fatal congenital heart defect (CHD) until the 1980s. Introduction of the Norwood procedure and subsequent Fontan operation significantly improved survival by creating a single-ventricle circulation. Due to the high mortality associated with the Norwood operation, neonatal orthotopic heart transplantation emerged as an alternative, despite challenges such as lifelong immunosuppressive treatment and uncertain longevity of transplanted hearts. Methods: A narrative review with a systematic literature search was conducted in the PubMed, following PRISMA guidelines and included studies of ethical and medical considerations, decision-making, counseling and treatment planning in children with HLHS. In addition, we manually screened reference lists to identify further relevant literature. We aimed to explore: how do ethical considerations and decision-making processes influence the management and outcomes of fetuses and neonates with HLHS and their families across prenatal, postnatal, and long-term care? Results: Of the 115 studies, 56 met the inclusion criteria. Early diagnosis through prenatal fetal ultrasound has markedly improved survival rates by enabling better parental awareness, counseling, and decision-making. Managing HLHS requires urgent, extensive, and costly medical interventions, with outcomes influenced by the healthcare system\u27s expertise, the experience of cardiologists and surgeons, ethical, legal, and religious considerations of the parents and medical team. The prenatal phase is crucial for optimal management, with advanced fetal ultrasound facilitating early detection. Postnatal care involves a multidisciplinary approach, including stage palliation physiology/surgery tailored to each patient. Despite surgical advancements, HLHS patients face higher morbidity and mortality rates than other patients with CHDs, with long-term survival and quality of life remaining key concerns. Ethical considerations play a significant role in the management of HLHS, encompassing the autonomy of families, the best medical interests of the child, societal, and cultural factors. Decision-making must balance full disclosure with sensitivity to parents\u27 values and beliefs. Conclusions: Management of HLHS involves multidisciplinary approach with complex medical and ethical considerations, but the current literature lacks high-quality studies or consensus guidelines on ethical decision-making. Therefore, the influence of ethical considerations on clinical management and patient care remains unclear, highlighting the need for further research
Highly efficient and selective one-step production of glycidol from glycerol using Cs/zeolite catalysts in a packed-bed reactor
Get PDFPrecipitation of water-insoluble copper salts in wood as protection against wood-decaying fungi
Get PDFV raziskavi predstavljamo metodo zaščite lesa pred glivnim razkrojem s precipitacijo netopnih bakrovih soli v lumnih lesnih celic z uporabo dvostopenjske impregnacije s topnim bakrovim sulfatom in fiksativom, natrijevim karbonatom. Fiksacija z natrijevim karbonatom se je izkazala kot učinkovita metoda za zmanjšanje izpiranja bakra iz vzorcev. Naravna kapaciteta zadrževanja bakra v beljavi bora je okoli 2000 ppm, kar smo določili z izpiranjem po metodi SIST EN 84. S fiksacijo smo uspešno zadržali v povprečju več kot 5000 ppm bakra v vzorcih in praktično preprečili izpiranje bakra iz vzorcev, impregniranih z 0,5-odstotno raztopino bakrovega sulfata (0,5 % ustreza koncentraciji bakrovih ionov v raztopini). Kljub zadostni koncentraci- ji se je pokazalo, da precipitirana oblika bakrovega karbonata v lesu ne deluje kot učinkovit fungicid, kar je verjetno posledica izjemno slabe topnosti v vodi, ki znaša < 0,005 g/L v sobnih razmerah. Izgube mase po testu SIST EN 113-1 kažejo na slabo zaščito pred gobo Coniophora puteana, vendar na zadovoljivo zaščito pred gobo Gloeophyllum trabeum.This study presents a method for protecting wood against fungal decay by precipitating insoluble copper salts within the lumina of wood cells using a two-step impregnation process. The procedure involves treatment with soluble copper sulfate followed by fixation with sodium carbonate. Fixation with sodium carbonate proved to be an effective method for reducing copper leaching from treated specimens. The natural retention capacity of copper in pine sapwood was around 2000 ppm, as determined by the leaching test according to SIST EN 84. With fixation, we successfully retained on average more than 5000 ppm of copper in the samples and almost completely prevented copper leaching from specimens impregnated with a 0.5% copper sulfate solution (0.5% corresponding to the concentration of copper ions in the solution). Despite sufficient copper concentration, the precipitated form of basic copper carbonate in the wood did not act as an effective fungicide, most likely due to its very low solubility in water (< 0.005 g/L at room temperature). Mass loss results according to SIST EN 113-1 indicated poor protection against Coniophora puteana and satisfactory protection against Gloeophyllum trabeum
Hydrological response to forest stand structure change triggered by natural disturbance in a torrential catchment
Get PDFVarovalna vloga gozdov je ključna, zlasti ob neizogibnih podnebnih spremembah, ki v alpskem svetu še povečujejo tveganje za hudourniške procese. Za analizo vpliva velikopovršinskih motenj na površinski odtok in hudourniške procese smo izbrali Dovški potok na južnem pobočju Karavank, kjer so bili v zadnjih desetih letih gozdovi zelo poškodovani. Z uporabo Kresnikove metode in hidrološkega modela ZEMOKOST smo določili pet scenarijev stanja gozda in ocenili različne razplete padavinskih dogodkov. Po enačbi Kresnik je stoletni pretok Dovškega potoka Q100 = 5,8 m³/s, medtem ko je bil leta 1961 izračunan Q100 = 6,0 m³/s. Z modelom ZEMOKOST smo za različne scenarije ugotovili različne rezultate. Leta 2015, pred vplivom motenj gozdov, je bil Q100 = 3,6 m³/s, in sicer 45 minut po začetku padavin. Leta 2019, po motnjah gozdov, pa se je Q100 povečal na 4,9 m³/s in se pojavil 39 minut po začetku padavin. Analiza hidravlične prevodnosti obstoječe hudourniške ureditve je pokazala, da le-ta ni več primerna glede na povečanje pretoka. Poleg tega smo na podlagi terenskih raziskav ugotovili, da erozijski drobir na območju pomeni nevarnost za nastanek drobirskih in blatnih tokov, kar bi lahko ogrozilo vas Dovje.The protective role of forests is crucial, especially in the face of unavoidable climate change, which increases the risk of torrential processes in the alpine environment. To analyse the effects of large forest disturbances on runoff and torrential processes, we chose the Dovski potok on the southern slope of the Karawanken Mountains, where forests have been severely damaged in the last decade. Using the Kresnik method and the hydrological model ZEMOKOST, five scenarios for the state of the forests were determined and different scenarios of precipitation events were evaluated. According to the Kresnik equation, the 100year discharge of the Dovski potok is Q100 = 5.8 m³/s, whereas n 1961 it was calculated as Q100 = 6.0 m³/s. The ZEMOKOST model provided different results for the different scenarios. In 2015, before the disturbances, the Q100 = 3.6 m³/s and occurred 45 minutes after the onset of the rainfall. In 2019, after the storms, Q100 increased to 4.9 m³/s and occurred 39 minutes after the onset of rainfall. Analysis of the hydraulic conductivity of the existing dams has shown that it is no longer sufficient to cope with the increase in runoff. In addition, on-site investigations have shown that the erosion debris deposits in the area harbour the risk of debris flows and mudslides that could endanger the village of Dovje
Functionality of potato virus Y coat protein in cell-to-cell movement dynamics is defined by its N-terminal region
Get PDFPotato virus Y (PVY) is one of the top 10 economically most important plant viruses and responsible for major yield losses. We previously suggested the involvement of the N-terminal region of PVY coat protein (CP) in PVY spread. By constructing different N-terminal deletion mutants of the PVY N605 strain, we here show that deletions of 40 or more amino acid residues from the N-terminal region of the CP resulted in the PVY multiplication limited to primary infected cells in Nicotiana clevelandii plants. Deletion of 26 residues profoundly impaired PVY cell-to-cell movement and prevented systemic PVY spread, while deletions of 19-23 residues allowed delayed systemic PVY spread. Introduced point mutations in the identified region prevent (S21G) or delay (G20P) PVY movement. In summary, this work shows the significance of the CP N-terminus for movement of the PVY
Endocrine adaptations to prolonged fasting women who had developed gestational diabetes
Get PDFObjectives: Intermittent fasting regimens that include periods of prolonged fasting may mimic certain well-documented benefits of calorie restriction. In this narrative review, we synthesize preclinical and human data on endocrine adaptations during prolonged fasting protocols. Methods: We conducted a structured search of relevant databases, followed by data extraction and synthesis, with a focus on endocrine adaptations during prolonged fasting and their potential implications for healthspan. Results: Across various endocrine axes, prolonged fasting appears to induce a reproducible pattern marked by diminished anabolic signaling and transient activation of potential stress resilience pathways. However, the evidence is limited by small sample sizes, short follow-up durations, methodological heterogeneity, and dependence on surrogate endpoints. Endocrine outcomes are frequently secondary and reported inconsistently. Potential risks include transient hypogonadism, relative hypothyroidism, hypercortisolemia, orthostatic intolerance, electrolyte imbalances, catabolic loss of lean mass, and refeeding challenges. Conclusions: Overall, prolonged fasting activates conserved endocrine mechanisms that may confer plausible cardiometabolic benefitshowever, their translation to clinical practice remains speculative. We highlight key knowledge gaps and propose directions for future research in this emerging field