Multi-locus genetic risk score predicts risk for Crohn's disease in Slovenian population

AIM: To develop a risk model for Crohn's disease (CD) based on homogeneous population.METHODS: In our study were included 160 CD patients and 209 healthy individuals from Slovenia. The association study was performed for 112 single nucleotide polymorphisms (SNPs). We generated genetic risk scores (GRS) based on the number of risk alleles using weighted additive model. Discriminatory accuracy was measured by area under ROC curve (AUC). For risk evaluation, we divided individuals according to positive and negative likelihood ratios (LR) of a test, with LR &gt; 5 for high risk group and LR &lt;0.20 for low risk group.RESULTS: The highest accuracy, AUC of 0.78 was achieved with GRS combining 33 SNPs with optimal sensitivity and specificity of 75.0% and 72.7%, respectively. Individuals with the highest risk (GRS &gt; 5.54) showed significantly increased odds of developing CD (OR = 26.65, 95% CI: 11.25-63.15) compared to the individuals with the lowest risk (GRS &lt;4.57) which is a considerably greater risk captured than in one SNP with the highest effect size (OR = 3.24). When more than 33 SNPs were included in GRS, discriminatory ability was not improved significantly; AUC of all 74 SNPs was 0.76.CONCLUSION: The authors proved the possibility of building accurate genetic risk score based on 33 risk variants on Slovenian CD patients which may serve as a screening tool in the targeted population.</p

Hipertermična intraperitonealna kemoterapija

V preteklosti so bolnike z zasevki po peritoneju obravnavali kot neozdravljivo bolne s terminalnim stanjem raka, ki se zdravi samo paliativno. Ob takšnem pristopu je bilo povprečno preživetje bolnikov le dva meseca. Zdravljenje teh bolnikov se je v devetdesetih letih prejšnjega stoletja pomembno spremenilo. Nekateri raziskovalci so bili namreč mnenja, da so peritonealni zasevki v določenih primerih samo vrsta loko-regionalne bolezni in se bolnik lahko (p)ozdravi. Eden glavnih zagovornikov te teorije in novega načina zdravljenja je bil Paul Sugarbaker. V sklopu zdravljenja se je začela uporabljati citoreduktivna kirurgija v kombinaciji z intraperitonealno kemoterapijo. Namen kirurškega posega je bila makroskopska odstranitev tumorja, nato pa z intraperitonealno kemoterapijo odstranitev še morebitnih mikroskopskih “preostankov” bolezni. Postopek, pri katerem citostatik med operacijo uvedemo in segrevamo, se imenuje hipertermična intraperitonealna kemoterapija. Hipertermija ima že sama po sebi protitumorski učinek na maligne celice, saj povzroči razgradnjo proteinov, aktivranje lizosomov in apoptozo. Ob segrevanju raztopine citostatika potečejo zapletene kemijske reakcije, ki dodatno povečajo njegovo učinkovitost in povečajo globino prodiranja zdravila v tumorsko tkivo. O najboljših rezultatih te oblike zdravljenja so poročali v primerih psevdomiksoma peritoneja, raka debelega črevesa in danke, karcinoma slepiča, karcinoma jajčnikov in peritonealnega mezotelioma. V prispevku avtorji predstavijo to zahtevno metodo zdravljenja, indikacije in vključitvena merila bolnikov ter sodobna spoznanja o učinkovitosti te metode za določene vrste raka

Analysis of phenotypical, molecular, and genetic properties of a novel triple-negative breast cancer cell line

Rak dojk je najpogostejši rak na svetu. Eden izmed njegovih podtipov je trojno negativni rak dojk (TNRD), za katerega je značilen agresiven potek, slabša prognoza in heterogenost. V svoji doktorski nalogi predstavim novo izolirano celično linijo TNRD, poimenovano MFUM-BrTNBC1. Linija je bila celovito karakterizirana (morfološko, fenotipsko, genotipsko). Za kontrole so služile komercialne celične linije z različnimi receptorskimi profili (MCF-7, MDA-MB-231, MDA-MB-453). Primerjalne morfološke analize so bile opravljene s pomočjo mikroskopije ter biomedicinske slikovne analize. S pomočjo imunocito/histokemičnih barvanj je bila preverjena izraženost hormonskih receptorjev (estrogen, progesteron), HER2, p53 in Ki-67 statusa. Ekspresija receptorjev je bila dodatno preverjena na transkripcijski ravni s qRT-PCR metodo. Dodatno je bilo opravljeno RNA sekvenciranje za molekularno analizo. Avtentičnost celičnih linij je bila preverjena s pomočjo STR profiliranja. MFUM-BrTNBC-1 celična linija je ohranila trojno negativni receptorski status in genetsko stabilnost do vsaj 6. pasaže. Rezultati STR analize in navzkrižna preverba z mednarodnimi bazami so dokazali avtentičnost celične linije. MFUM-BrTNBC1 se je po morfologiji celic razlikovala tudi od TNRD celične linije MDA-MB-231. Razlike od komercialne linije, predstavljajo tudi glavne prednostne lasnosti MFUM-BrTNBC-1. Te so izolacija iz primarnega tumorskega tkiva, popoln izvorni zapis, mednarodno poimenovanje, celoten in edinstven STR profil ter genetska stabilnost do vsaj 6. pasaže.Breast cancer is the most common cancer worldwide. One of its subtypes is triple-negative breast cancer (TNBC), which is aggressive, has a worse prognosis, and is heterogeneous. In this thesis, I present a newly isolated TNBC cell line MFUM-BrTNBC-1. We performed a detailed characterization of morphological, phenotypic, and genotypic characteristics. As controls served 3 commercial breast cancer cell lines with different receptor profiles (MCF-7, MDA-MB-231, MDA-MB-453). Comparative morphological analysis was done using microscopy (light, fluorescence) and biomedical image analysis. Hormone receptor (estrogen, progesterone), p53 and Ki-67 statuses were determined by immunocyto/histochemical tests. Receptor expression was validated at the transcriptional level by qRT-PCR. RNA sequencing was utilised for additional analysis of molecular properties. Authenticity was checked by STR profiling. MFUM-BrTNBC-1 maintained the primary triple-negative receptor status and was genetically stable up to the 6th passage. STR profiles were crosschecked with international databases and confirmed authenticity. Morphologically, MFUM-BrTNBC-1 differed from the commercial TNBC cell line MDA-MB-231. The key differences and simultaneously advantages between MFUM-BrTNBC-1 and the commercial cell are, isolation from a primary tumourgood growth characteristicsidentical phenotype to primary tissuecomplete origin records, unique identifiercomplete, unique STR profile and genetic stability up to (at least) 6th passage

Novel Methacrylate-Based Multilayer Nanofilms with Incorporated FePt-Based Nanoparticles and the Anticancer Drug 5-Fluorouracil for Skin Cancer Treatment

Despite medical advances, skin-associated disorders continue to pose a unique challenge to physicians worldwide. Skin cancer is one of the most common forms of cancer, with more than one million new cases reported each year. Currently, surgical excision is its primary treatment; however, this can be impractical or even contradictory in certain situations. An interesting potential alternative could lie in topical treatment solutions. The goal of our study was to develop novel multilayer nanofilms consisting of a combination of polyhydroxyethyl methacrylate (PHEMA), polyhydroxypropyl methacrylate (PHPMA), sodium deoxycholate (NaDOC) with incorporated superparamagnetic iron&ndash;platinum nanoparticles (FePt NPs), and the potent anticancer drug (5-fluorouracil), for theranostic skin cancer treatment. All multilayer systems were prepared by spin-coating and characterised by atomic force microscopy, infrared spectroscopy, and contact angle measurement. The magnetic properties of the incorporated FePt NPs were evaluated using magnetisation measurement, while their size was determined using transmission electron microscopy (TEM). Drug release performance was tested in vitro, and formulation safety was evaluated on human-skin-derived fibroblasts. Finally, the efficacy for skin cancer treatment was tested on our own basal-cell carcinoma cell line

DYNAMIC ANALYSIS OF WIND FARM OPERATION INTEGRATED IN POWER SYSTEM BASED ON SYNCHRONIZED MEASUREMENTS

Pouzdano i sigurno vođenje elektroenergetskog sustava (EES) ovisi o dobrom poznavanju strujno-naponskih prilika tijekom normalnih i izvanrednih pogonskih stanja. Poznavanje odziva EES-a u realnom vremenu s obzirom na dinamičke poremećaje uzrokovane karakterističnim događajima, posebno je važno za dobro vođenje EES-a. Vjetroelektrana VE Vrataruša trenutačno je jedina vjetroelektrana priključena na prijenosnu mrežu hrvatskog EES-a. U radu je analiziran utjecaj VE Vrataruša na prijenosnu mrežu Prijenosnog područja Rijeka. Provedeni su statički proračuni (proračun tokova snaga i proračun struja kratkog spoja) te dinamička analiza (prijelazne pojave), prilikom čega su obuhvaćena normalna, izvanredna i havarijska pogonska stanja te njihov utjecaj na rad zaštite i stabilnost sustava. Kao podloga za analizu poslužio je matematički model EES-a PrP Rijeka, zasnovan i verificiran na osnovi sinkroniziranih mjerenja fazora napona i struje.Reliable and safe control of the power system is based on knowing current and voltage conditions during normal and irregular states. Real time dynamic disturbance responses, caused by characteristic events, are especially important. Wind farm Vrataruša is currently the only wind farm connected to the Croatian transmission system. This paper focuses on the impact of the wind farm Vrataruša on the system in the transmission area Rijeka. Static calculations (power flow calculation and short circuit current calculation) and dynamic analyses (transient phenomena) comprise normal, irregular and outage operational states, as well as their impact on a protection system and on overall power system stability. Analyses are based on a mathematical model of the transmission system area Rijeka, verified by synchronized voltage and current phasor measurements