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Induced pluripotent stem cells in drug discovery
No full textInducirane pluripotentne matične celice so v zadnjih letih postale pomembno orodje za odkrivanje zdravilnih učinkovin, saj ponujajo bistvene prednosti pred tradicionalnimi modeli, kot so primarne celice, rakave celične linije in živalski modeli. Pridobimo jih z reprogramiranjem somatskih celic v pluripotentno stanje, kar omogoča njihovo diferenciacijo v različne tipe celic ob ohranjanju dedne informacije posameznika. Pri uporabi induciranih pluripotentnih matičnih celic za odkrivanje zdravilnih učinkovin je na voljo več modelov, vključno z dvodimenzionalnimi kulturami, enostavnejšimi tridimenzionalnimi modeli in naprednejšimi modeli – organi na čipu. Tovrstni modeli omogočajo natančnejšo oceno toksičnosti in učinkovitosti zdravilnih učinkovin, njihovih medsebojnih interakcij ter proučevanje mehanizmov bolezni. Izzivi, s katerimi se soočamo ob uporabi induciranih pluripotentnih matičnih celic, so: njihova nezadostna zrelost, variabilnost med pridobljenimi celičnimi linijami in visoki stroški, kar trenutno omejuje njihovo širšo uporabo v farmaciji. Kljub tem omejitvam imajo inducirane pluripotentne matične celice velik potencial za razvoj personaliziranih oblik zdravljenja in odkrivanje novih terapevtskih pristopov.Induced pluripotent stem cells have become an important tool for drug discovery in recent years, offering significant advantages over traditional models, such as primary cells, cancer cell lines, and animal models. These cells are derived by reprogramming somatic cells into a pluripotent state, allowing differentiation into various cell types while retaining the genetic information of the individual. In drug discovery, models from induced pluripotent stem cells encompass twodimensional cultures, three-dimensional models, and more sophisticated organs-on-a-chip. These advanced models enable more accurate assessment of drug toxicity and efficacy, compound interactions, as well as detailed studies of disease mechanisms. however, challenges in application of induced pluripotent stem cells remain, including limited cellular maturity, variability across obtained cell lines, and high costs, which currently restrict their broader use in the pharmaceutical field. Despite these limitations, induced pluripotent stem cells hold great promise for the development of personalised therapies and the discovery of novel therapeutic approaches
Modern radiotherapy: all-in on number 5 - no more bets
Get PDFRazvoj sodobne radioterapije poteka popolnoma v skladu z načelom Citius, Altius, Fortius (hitreje, višje, močneje), hkrati pa sledi tudi filozofiji »manj je več«. V zadnjih letih se je režim radioterapije v petih frakcijah pokazal kot inovativen pristop, ki ponuja krajše zdravljenje, večjo natančnost in boljšo terapevtsko učinkovitost, ob tem pa zmanjšuje porabo sredstev namenjenih za zdravljenje. Dokazi iz obsežnih prospektivnih študij so potrdili učinkovitost tega pristopa pri zdravljenju raka dojke, prostate, pljuč in danke ter pri zdravljenju oligometastatske bolezni. Poleg tega je bil tehnološki napredek na področju slikanja, stereotaktičnih tehnik in samega obsevanja ključnega pomena za zagotavljanje varnosti ter natančnosti tega zdravljenja. Poleg klinične učinkovitosti so prednosti obsevanja v petih frakcijah tudi izboljšanje kakovosti življenja bolnikov, zmanjšanje bremena zdravljenja in povečanje učinkovitosti zdravstvenega varstva. V dobi sodobne radioterapije prevladuje Citius, Altius, Fortius – ker manj pomeni več, prihodnost pa je zdaj.The evolution of modern radiotherapy aligns seamlessly with the principles of Citius, Altius, Fortius—faster, higher, stronger— while embracing the Less is More philosophy. In recent years, the 5-fraction radiotherapy regimen has emerged as a transformative approach, offering shorter treatment durations, higher precision, and enhanced therapeutic efficacy, all while optimizing healthcare resources. Evidence from large prospective trials has confirmed its efficacy in breast, prostate, lung, and rectal cancers, as well as in the management of oligometastatic disease. Furthermore, technological advancements in imaging, stereotactic techniques, and dose delivery have played a crucial role in ensuring the safety and precision of these treatments. Beyond clinical efficacy, the benefits of 5-fraction radiotherapy extend to improving patient quality of life, reducing treatment burden, and enhancing healthcare efficiency. In the era of modern radiotherapy, Citius, Altius, Fortius prevails—because Less is More, and the future is now
Chemotherapy induced peripheral nevropathy (CIPN)
Get PDFSistemsko zdravljenje dokazano izboljša preživetje številnih
bolnikov z rakom. Nabor protirakavih zdravil se je v zadnjih
desetletjih močno povečal, z njimi zdravimo več kot polovico
obolelih. Specifičnost bolezni, specifičnost zdravljenja in zdravil, ki imajo pogosto zelo ozko terapevtsko okno, so zahtevale razvoj nove, od klasične interne medicine ločene specializacije, internistične onkologije. Specializacija iz internistične onkologije je kot samostojna veja specializacije iz interne medicine v Sloveniji priznana od leta 2000. Pojavnost raka v Sloveniji narašča, vse več je bolnikov, ki potrebujejo tudi sistemsko zdravljenje in obravnavo pri internistu onkologu. Žal pa skladno z rastjo števila bolnikov ne raste tudi število internistov onkologov, premajhne postajajo tudi obstoječe prostorske zmogljivosti.Systemic therapy has been shown to improve survival in many cancer patients. The number of anticancer drugs has increased dramatically in recent decades and more than half of all cancer patients are treated with these drugs. The specificity of the disease, the specificity of the treatment, and the drugs, which often have a very narrow therapeutic window, have necessitated the development of a new specialty, medical oncology, separate from internal medicine. Since 2000, medical oncology has been recognized in Slovenia as an independent specialization separate from internal medicine. The incidence of cancer in Slovenia is increasing, and there are more and more patients who need systemic treatment and management by medical oncologists. Unfortunately, the number of oncologists is not increasing at the same rate as the number of patients, and the existing facilities are becoming inadequate
Netnography as a methodological lens for uncovering heritage ambience
Get PDFKonstrukt turizma je prelomna oblika kapitalistične produkcije prostora, ki ustvarja nove urbane oblike. V številnih arhitekturnih in morfoloških študijah so analizirali različne modele, manjkajo pa primerjave njihovih značilnosti. Avtorji so v članku primerjali štiri vrste turizma, povezane z razvojem kapitalizma (vključno s predfordizmom, fordizmom in postfordizmom), in različne vrste turističnih mest. V povezavi z gospodarskimi, socialnimi in kulturnimi značilnostmi so analizirali njihovo arhitekturno ikoničnost, morfološke vzorce in prostorsko metriko. Izsledki kažejo, da predfordistični in fordistični konstrukti turizma, za katere je značilna visoka gostota zazidave, spodbujajo družbene odnose in povečujejo sposobnost ustvarjanja mesta, postfordistični konstrukti turizma z nizko gostoto zazidave pa povzročajo višje okoljske stroške (porast zasebnih zelenih in vodnih površin) in višje družbene stroške zaradi arhitekturne ikoničnosti. Avtorji so proučevali povezavo med arhitekturnimi in urbanističnimi spremenljivkami, ki bi jih bilo treba upoštevati pri načrtovanju turističnih destinacij v okviru kapitalistične produkcije turističnega prostora.The concept of heritage ambience reconfigures cultural preservation by prioritizing multisensory experiences and human subjectivity, transcending static architectural analysis. However, capturing these intangible dimensions – rooted in sensory engagement, memory, and local narratives – remains methodologically challenging. This study employs netnography to decode interactions between sensory atmospheres and collective memory in historic urban spaces, using the medina in Tlemcen, Algeria, as a case study. Analysis of digital narratives, social media discourses, and community-generated content reveals how nonexpert knowledge reconstructs heritage values often marginalized by traditional conservation frameworks. The results demonstrate that the medina’s ambience is not merely a backdrop but a dynamic archive of lived experiences, where smells, sounds, and textures intertwine to shape cultural identity. This research advocates integrating local perspectives into protection strategies, challenging the hegemony of institutional approaches. By linking digital ethnography and sensory urbanism, it proposes a reproducible methodological framework for reimagining heritage as a living, participatory practice where the spirit of place thrives through community governance
Explicit microrelief-controlled decoupling of initial aerobic decay and leaching (in hummocks) and anaerobic decay (in hollows) in surface layers of a Sphagnum-dominated peatland
Get PDFUnderstanding decay processes in peat deposits is fundamental for predicting their role as sources or sinks of atmospheric carbon in a changing environment. It is known that the distribution of microhabitats –hummock, lawn and hollow– within peatlands affects organic matter quality and degradation, but microtopography-dependent carbon dynamics are poorly understood on the molecular level. We studied early decomposition across microtopography levels through analyses of superficial moss cores from a Sphagnum-dominated ombrotrophic peatland in Central Germany, and a 400-day incubation experiment, using analytical pyrolysis. Interpretations were aided by analysis of living vegetation and a deep peat core as reference. Stable and labile pools of polysaccharides dominated the pyrolyzates and played a crucial role in decay dynamics. Two distinct degradation processes emerged: 1) anaerobic decay, characterized by loss of polysaccharides and selective preservation of lignin and aliphatic OMand 2) leaching of labile phenolic compounds (including sphagnum acid) and free carbohydrates with concomitant initial aerobic degradation and selective preservation of structural polysaccharides. The relative importance of these initial decay processes is spatially dependentanaerobic decay was detectable in only some of the more evolved hollow layers, while aerobic degradation and leaching dominated in hummocks. Sphagnum acid’s molecular markers appeared useful tracers of early decay as it probably has a leaching-sensitive component in hyaline cells (corroborated by SEM micrographs) that is lost rapidly from hummocks, but not from hollows. Hence, the occurrence of sphagnum acid in peat cores is influenced by microrelief position during peat accretion. This study highlights how microhabitat variations within peatlands influence decay mechanisms on the molecular level
