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Attitudes of pharmacists in Croatia towards the independent pharmacist prescribing program
No full textPosljednjih desetljeća farmaceutska struka prolazi kroz značajne promjene diljem svijeta, s naglaskom na proširenje uloga
ljekarnika izvan tradicionalnih okvira izdavanja lijekova. Jedan od smjerova takvih promjena je i koncept samostalnih
farmaceuta propisivača (eng. Independent pharmacist prescriber) koji je uspješno implementiran u nekoliko zemalja svijeta.
Samostalnim farmaceutima propisivačima u Velikoj Britaniji, u 2024. godini, dopušteno je procijeniti pacijente, postaviti
dijagnozu i propisati lijek za bilo koje stanje ili bolest (isključujući diamorfin, kokain i dipipanon), te za bilo kojeg pacijenta
unutar njihovih kliničkih kompetencija. Opseg djelovanja ovih farmaceuta širok je i obuhvaća rad na razini primarne i
sekundarne zdravstvene zaštite.
Cilj ovog istraživanja bio je utvrditi stavove hrvatskih ljekarnika prema programu samostalnih farmaceuta propisivača (eng.
Independent pharmacist prescriber). Putem on-line anketnog upitnika ispitanici su mogli izraziti svoje stavove prema
programu, njegovim prednostima i nedostatcima, ali i njegovoj potencijalnog implementaciji i izvođenju u Republici
Hrvatskoj.
U istraživanju je sudjelovalo 455 ispitanika, od kojih je 82,6% bilo žena, a 17,4% muškaraca, te je medijan dobi iznosio 34
godine. Većina ispitanika (85,5%) smatra da bi propisivanje lijekova od strane farmaceuta imalo pozitivan utjecaj na
zdravstveni sustav. Također, svaka navedena prednost ocijenjena je većinski kao iznimno važna. „Neprihvaćanje od strane
liječnika“ hrvatski su ljekarnici ocijenili kao najveću prepreku u okviru potencijalne implementacije programa, a „Vremenska
ograničenja“ kao najmanju. Gotovo su svi ispitanici smatrali kako uloga farmaceuta kao propisivača lijekova predstavlja
profesionalno napredovanje, a 63,5% ispitanika u potpunosti se složilo kako bi postali samostalni farmaceuti propisivači, kada
bi to bila mogućnost. Dodatna obuka nakon fakulteta, specijalistički studij i kurikulum fakulteta bili su najčešći odgovori na
pitanje gdje i na koji način bi se trebala odvijati obuka za stjecanje titule samostalnog farmaceuta propisivača.
Zaključno, stav hrvatskih ljekarnika prema programu samostalnih farmaceuta propisivača (eng. Independent pharmacist
prescriber) vrlo je pozitivan i optimističan, a približno dvije trećine ljekarnika izrazilo je želju za postizanjem titule
samostalnog farmaceuta propisivača. Ovi rezultati sugeriraju želju hrvatskih ljekarnika za daljnjim napredovanjem i
usavršavanjem, te upućuju na potrebu za raspravom o potencijalnim proširenjima uloga ljekarnika u sklopu hrvatskog
zdravstvenog sustava.In recent decades, the pharmaceutical profession has undergone significant changes worldwide, with a focus on
expanding the roles of pharmacists beyond the traditional framework of dispensing medications. One direction of these
changes is the concept of independent pharmacist prescribers, which has been successfully implemented in several
countries worldwide. In the UK, as of 2024, independent pharmacist prescribers are allowed to assess patients, diagnose,
and prescribe medications for any condition or illness (excluding diamorphine, cocaine, and dipipanone), as well as for
any patient within their clinical competence. The scope of these pharmacists' work is broad, covering both primary and
secondary healthcare.
The aim of this research was to determine the attitudes of Croatian pharmacists towards the independent pharmacist
prescriber program. Through an online survey, respondents were able to express their views on the program, its
advantages and disadvantages, as well as its potential implementation and execution in Croatia.
The study involved 455 respondents, 82.6% of whom were women, and 17.4% men, with a median age of 34. Most
respondents (85.5%) believe that pharmacist prescribing would have a positive impact on the healthcare system.
Additionally, all listed advantages were predominantly rated as extremely important. "Lack of acceptance by doctors"
was seen by Croatian pharmacists as the biggest obstacle to the potential implementation of the program, while "Time
constraints" were considered the smallest obstacle. Nearly all respondents believed that the role of pharmacists as
prescribers represents professional development, and 63.5% strongly agreed that they would become independent
pharmacist prescribers if given the opportunity. Postgraduate training, specialist studies, and university curriculum were
the most common answers regarding how and where the training for achieving the title of independent pharmacist
prescriber should take place.
In conclusion, the attitudes of Croatian pharmacists towards the independent pharmacist prescriber program are very
positive and optimistic, with approximately two-thirds expressing a desire to obtain the title. These results suggest a
strong willingness for further professional development and point to the need for discussions on potential expansions of
pharmacists' roles within the Croatian healthcare system
Optimization of fragmentation conditions for deuterated letrozole and deuterated ribociclib in a triple quadrupole mass spectrometer
No full textRibociklib je antineoplastik indiciran za liječenje postmenopauzalnih žena s lokalno uznapredovalim ili metastatskim
rakom dojke koji je HR pozitivan i HER2 negativan. Koristi se u kombinaciji s hormonskom terapijom koja smanjuje
učinak estrogena, a jedan od takvih lijekova je letrozol (inhibitor aromataze). Prilikom razvoja bioanalitičkih metoda
za terapijsko praćenje ovih lijekova ključna je uporaba unutarnjih standarda, koji eliminiraju pogreške nastale tijekom
pripreme uzorka za analizu. Optimalni unutarnji standard za tu svrhu jest izotopski označena verzija molekule koju
se želi kvantificirati, pri čemu se preferira upotreba deuterija zbog izobilja vodika u organskim molekulama. Glavni
cilj ovog istraživanja bio je optimizirati uvjete fragmentacije za deuterirani letrozol i deuterirani ribociklib koristeći
spektrometar masa s trostrukim kvadrupolom. Optimizacija je uključivala određivanje optimalnog fragmentorskog
napona, odabir fragmenata s najintenzivnijim signalom te određivanje optimalnih kolizijskih energija za generiranje
tih fragmenata. Pozitivna elektrosprej ionizacija deuteriranog letrozola formira molekulski ion s m/z 290,1. Optimalni
fragmentorski napon od 80 V daje najveći intenzitet signala tog molekulskog iona. Fragmenti m/z vrijednosti 194,2 i
221,0 najpogodniji su za analizu, s optimalnim kolizijskim energijama od 40 eV i 10 eV. Deuterirani ribociklib u
ionskom izvoru daje molekulski ion s m/z 441,2, pri čemu optimalni fragmentorski napon iznosi 160 V. Optimalni
fragmenti m/z 322,1, 252,2, 294,1 i 373,1 imaju najveći intenzitet signala pri kolizijskim energijama od 35 eV, 60
eV, 45 eV i 20 eV. Istraživanje je također pokazalo da je pozitivna elektrosprej ionizacija učinkovitija za analizu ovih
deuteriranih spojeva u usporedbi s negativnom elektrosprej ionizacijom jer generira fragmente s većim intenzitetom
signala.Ribociclib is an antineoplastic indicated for treating postmenopausal women with locally advanced or metastatic breast cancer that is HR-positive and HER2-negative. It is used in combination with hormone therapy that reduces the effect of estrogen, one such drug being letrozole (an aromatase inhibitor). During the development of bioanalytical methods for
therapeutic monitoring of these drugs, the use of internal standards is crucial to eliminate errors arising during sample
preparation for analysis. The optimal internal standard for this purpose is an isotopically labeled version of the molecule
to be quantified, with deuterium being preferred due to the abundance of hydrogen in organic molecules.The main aim of
this research was to optimize fragmentation conditions for deuterated letrozole and deuterated ribociclib using a triple
quadrupole mass spectrometer. Optimization involved determining the optimal fragmentor voltage, selecting the
fragments with the most intense signal, and determining the optimal collision energies to generate these fragments.
Positive electrospray ionization of deuterated letrozole forms a molecular ion with m/z 290.1. An optimal fragmentor
voltage of 80 V gives the highest signal intensity for this molecular ion. Fragments with m/z values of 194.2 and 221.0 are
most suitable for analysis, with optimal collision energies of 40 eV and 10 eV. Deuterated ribociclib in the ion source
gives a molecular ion with m/z 441.2, with an optimal fragmentor voltage of 160 V. Optimal fragments with m/z 322.1,
252.2, 294.1, and 373.1 have the highest signal intensity at collision energies of 35 eV, 60 eV, 45 eV, and 20 eV. The
research also showed that positive electrospray ionization is more effective for analyzing these deuterated compounds
compared to negative electrospray ionization, as it generates fragments with more intense signals
Development of a numerical model of water flow through the unsaturated zone of the Zagreb aquifer in the area of Velika Gorica wellfield : doctoral thesis
No full textOdrživo korištenje i upravljanje zagrebačkog vodonosnika kao strateškog resursa Republike Hrvatske, između ostalog, zahtijeva i identifikaciju i kvantifikaciju svih izvora njegovog prihranjivanja. U cilju kvantifikacije prihranjivanja vodonosnika iz oborine, kao jednog od izvora prihranjivanja, izrađeno je nekoliko je numeričkih dvodimenzionalnih modela tečenja vode i trasiranja čestica kroz nesaturiranu zonu zagrebačkog vodonosnika na području vodocrpilišta Velika Gorica. Pri definiranju geometrije, parametara, početnih i rubnih uvjeta, te za kalibraciju modela korišteni su podaci prikupljeni na istraživačkom poligonu koji se nalazi u prvoj zoni sanitarne zaštite zdenca B-1 vodocrpilišta. Na poligonu se kontinuirano mjere parametri nesaturirane zone pomoću TDR (engl. Time Domain Reflectometry) sondi te meteorološki uvjeti, a izvedena su i geofizička istraživanja te nekoliko eksperimenata trasiranja. Rezultati prognoznog modela za razdoblje od 8. 11. 2019. do 8. 5. 2023. utvrdili su količinu prihranjivanja vodonosnika iz oborine od 16 % i brzinu procjeđivanja oborine od tri godine i tri mjeseca, od trenutka infiltracije na površini terena do razine podzemne vode. Prognoznim modelom za buduće razdoblje (2019. - 2040.) predviđena je dvostruko veća količina procjeđivanja od 36 % što je u skladu s povećanjem učestalosti oborine u razdoblju do 2040. godine. Veća učestalost oborine uzrokovala je i kraće vrijeme procjeđivanja oborine, odnosno godinu dana i četiri mjeseca. Modelima tečenja, kontinuiranim mjerenjima parametara nesaturirane zone na istraživačkom poligonu i eksperimentima trasiranja utvrđeni su faktori koji utječu na količine i brzine procjeđivanja vode u nesaturiranoj zoni: učestalost, količina i intenzitet oborine, sadržaji vode u nesaturiranoj zoni neposredno prije oborinskog događaja, zatim heterogenost naslaga te pojava preferencijalnog tečenja. Pouzdano definiranje rubnog uvjeta infiltracije vode iz oborine do podzemne vode omogućava unaprjeđenje regionalnih numeričkih modela tečenja podzemne vode, a model tečenja vode kroz nesaturiranu zonu temelj je za buduće modele pronosa onečišćenja s površine do podzemne vode.Sustainable management of the Zagreb aquifer, as a strategic resource of the Republic of Croatia, requires identifying and quantifying all sources of its recharge. In order to identify and quantify the recharge from precipitation, as one of the sources of recharge, a numerical two-dimensional model of water flow through the unsaturated zone was built in the area of the Velika Gorica wellfield. A research polygon, consisting of a meteorological station and a shaft, has been established at the Velika Gorica wellfield, where the parameters of the unsaturated zone are continuously measured at different depths using TDR (Time Domain Reflectometry) probes. Geophysical measurements were performed on the surface next to the shaft itself, and the method was electrical resistivity tomography. The measurements performed at the research polygon were used to define the unsaturated flow model geometry, parameters, initial and boundary conditions, and also for model calibration. The results of the flow model for the period from 11/8/2019 to 5/8/2023 pointed out that the precipitation contributes to aquifer recharge by 16 % amount in average. However, that amount varies greatly from year to year. For example, in the one-year periods from 11/8/2019 to 11/8/2020 and from 11/8/2020 to 11/8/2021, the aquifer recharge from precipitation amounts 20 and 19 %, while in the period from 11/8/2021 to 11/8/2022, that percentage is only 2%. The small amount of aquifer recharge from precipitation in 2022 is the result of relatively longer previous dry periods. In 2020, 17% less precipitation occurred than the multi-year average, in 2021 26% less, and in 2022 even 30% less. On top of that, 2022 was an above-average dry year. The most significant amounts aquifer recharge from precipitation occurs at the end and beginning of the year, that is, from December to April, depending on the hydrological year. The periods of significant aquifer recharge from precipitation coincide with the periods of high groundwater levels, high water contents in the unsaturated zone and low values of evapotranspiration. The results of the particle tracking model for the period from 11/8/2019 to 5/8/2023 showed a relatively long travel time of precipitation from the infiltration moment on the ground surface to the moment it reaches the groundwater, i.e., 3 years and 3 months. The factor that most affects the rather slow percolation of precipitation is dry hydrological conditions, that is, below-average amounts of precipitation and their unfavorable distribution (a small number of hours with precipitation). Other factors that affect precipitation percolation and cannot be ignored considering the research location are the heterogeneity of the observed unsaturated zone profile the appearance of preferential flow. The water flow forecast model for the future period (2019 – 2040) predicts a 36 % as the amount of aquifers recharge from precipitation, which is twice as much as the amount simulated by the model for the period from 11/8/2019 to 5/8/2023, which is in accordance with the predicted increase of the precipitation frequency in the future climate. Accordingly, particle tracking model simulated a much shorter travel time of precipitation through the unsaturated zone, i.e. 1 year and 4 months. Unsaturated flow models, continuous measurements of parameters of the unsaturated zone, as well as tracer experiments, showed that the amount of aquifer recharge from precipitation and the travel time of precipitation in the unsaturated zone from the ground surface to the groundwater is affected by the frequency, amount and intensity of precipitation, the water contents in the unsaturated zone before the precipitation event, then the heterogeneity of the observed unsaturated deposit and the appearance of preferential flow. Knowledge of the amounts and rates of precipitation and also of the percolation precipitation process through the unsaturated zone enables the quantification of aquifer recharge from precipitation, which further enables the improvement of regional groundwater flow models, by reliable definition of the boundary condition represented by aquifer recharge from precipitation. Additionally, the unsaturated flow model represents the basis for future models of contaminant transport through the unsaturated zone
Aeroplane take-off method with reduced jet engine power
No full textAvioni koji se koriste prvobitno u civilne svrhe u velikom značaju ovise o načinu i kvaliteti, kako planskog tako i linijskog održavanja. Cilj ovog rada je usporediti metodu polijetanja sa štednim potiskom s utjecajem nekolicine polijetanja s maksimalnim mogućnostima mlaznog motora. Analiziraju se podaci realnih ciklusa aktivne aviokompanije u usporedbi s teorijskim saznanjima. U tim podacima analizira se teorijska sila potiska i sila potiska koja je dobivena metodom polijetanja s štednim potiskom. Utjecaj glavnog parametra za praćenje ekonomski isplativog održavanja će pokazati koliko je efektivno stanje mlaznog motora poboljšano u periodu kada se koristi štedna metoda. U zadnjim dijelovima rada, analizirane su prednosti, nedostatci i ekonomska isplativost takvog načina operiranja avionom.Aircraft originally used for civil purposes largely depend on the method and quality of both scheduled and routine maintenance. The aim of this paper is to compare the method of fuel-efficient thrust takeoff with the impact of multiple takeoffs using the jet engine's maximum capabilities. Data from real cycles of an active airline are analyzed and compared with theoretical knowledge. In these data, the theoretical thrust force is analyzed alongside the thrust force obtained using the fuel-efficient thrust takeoff method. The impact of the main parameter for monitoring cost-effective maintenance will demonstrate how much the engine's performance improves during the period when the fuel-saving method is applied. In the final sections of the paper, the advantages, disadvantages, and economic feasibility of this aircraft operating method are analyzed
Adaptation and a study of Learning to BREATHE mindfulness for students program effectiveness
No full textTijekom posljednja dva desetljeća u svijetu je došlo do povećanja broja istraživanja u području prakse usredotočene svjesnosti (eng. mindfulness) te intenzivnijeg kreiranja i provedbe programa namijenjenih adolescentima koji se temelje na metodama i tehnikama mindfulness prakse. Američki Learning to BREATHE program jedan je od često implementiranih mindfulness programa namijenjenih adolescentima. Sudionici spomenutog programa pokazuju niže razine percipiranog stresa i psihosomatskih pritužbi, više razine učinkovitosti u afektivnoj regulaciji te pozitivan učinak na regulaciju emocija, uključujući emocionalnu svijest, jasnoću i pristup strategijama regulacije nakon sudjelovanja u programu (Broderick i Metz, 2011; Metz, 2013). Svrha ovoga diplomskog rada je pružiti prikaz procesa adaptacije i implementacije Learning to BREATHE programa u Republici Hrvatskoj na populaciji studenata Sveučilišta u Zagrebu. Ciljevi rada bili su opisati proces adaptacije 6-tjednog Learning to BREATHE programa, provesti pilot studiju učinka provedenog programa, ispitati percepciju prikladnosti i kvalitete programa od strane polaznika te kreirati smjernice za unapređenje programa u hrvatskom kontekstu. Detaljni opis koraka koji su poduzeti kako bi se program prilagodio kulturnim, jezičnim i kontekstualnim specifičnostima populacije hrvatskih studenata obuhvaćeni su ovim radom. U istraživanju prikladnosti i pilot studiji učinka programa „Valovi uma“ korištena je kvantitativna (N=9) i kvalitativna (N=3) metodologija. Provedeno je pilot online istraživanje prije i nakon provedbe programa kako bi se procijenili učinci programa. Prikazane su razlike u mentalnoj dobrobiti, ruminaciji, samoregulaciji, stresu, depresivnosti, anksioznosti, samosuosjećanju, pozitivnom i negativnom afektu te suočavanju sa stresom kod studenata koji su sudjelovali u programu. Dodatno, nakon sudjelovanja u programu, provedena su i tri intervjua, što je omogućilo dublje razumijevanje programa i pružilo uvid u iskustva sudionika. Doprinos ovog rada ogleda se u potencijalnoj primjeni znanstveno utemeljenih i na dokazima utemeljenih mindfulness intervencija s populacijom hrvatskih studenata.Over the past two decades, there has been an increase in research worldwide in the field of mindfulness-based practices and the more intensive creation and implementation of programs aimed at adolescents based on methods and techniques of mindfulness practice. The American Learning to BREATHE program is one of the frequently implemented mindfulness programs for adolescents. Participants in this program demonstrate lower levels of perceived stress and psychosomatic complaints, higher levels of effectiveness in affective regulation, and a positive impact on emotion regulation, including emotional awareness, clarity, and access to regulation strategies after participating in the program (Broderick & Metz, 2011; Metz, 2013). The purpose of this master's thesis is to provide an overview of the adaptation and implementation process of the Learning to BREATHE program in the Republic of Croatia among the student population of the University of Zagreb. The objectives of the study were to describe the process of adapting the 6-week Learning to BREATHE program, conduct a pilot study on the program's effects, examine participants' perceptions of program suitability and quality, and create guidelines for program improvement in the Croatian context. A detailed description of the steps taken to adapt the program to the cultural, linguistic, and contextual specificities of the Croatian student population is covered in this work. Quantitative (N=9) and qualitative (N=3) methodology was used in the suitability assessment and pilot study of program effects. A pilot online survey was conducted before and after program implementation to assess its effects. Differences in mental well-being, rumination, self-regulation, stress, depression, anxiety, self-compassion, positive and negative affect, and stress coping among students who participated in the program were presented. Additionally, three interviews were conducted after participation in the program, allowing for a deeper understanding of the program and insight into participants' experiences. The contribution of this work lies in the potential application of scientifically and evidence-based mindfulness interventions with the population of Croatian students
Reduction of carbon footprint of small-scale fishing vessels
No full textU ovom diplomskom radu analizirana je hrvatska flota brodova za mali prionbalni ribolov. Izračunat je godišnji ugljični otisak hrvatske flote brodova duljine do 12 metara. Na primjeru jednog broda provedene su analize cjeloživotnih emisija (eng. Life Cycle Assesment, LCA) i analize cjeloživotnih troškova (eng. Life Cycle Cost Assesment, LCCA) za životni vijek od 30 godina. Razmatrane su varijante poput potpuno električnog broda, hibridno električnog, pogona na ukapljeni plin (eng. Liquified Natural Gas, LNG), biodizel i broda s pogonom na metanol. Predložena rješenja zatim su uspoređena s referentnim dizelskim pogonom. U svrhu boljeg uvida u predložena rješenja, provedene su i analize povrata investicija te analiza osjetljivosti na promjene cijena energenata. Ugljični porez po trenutnom zakonu obuhvaća samo brodove preko 5000 bruto registarskih tona. S obzirom da se brod promatra kroz period od 30 godina u kojem može doći do promjene zakona, provedena je i LCCA analiza u slučaju uvođenja ugljične poreza. Rezultati LCCA pokazuju da je cjenovno dizelski brod najpovoljniji, ali druga rješenja relativno malo odstupaju. LCA pokazuje da je potpuno električni brod ekološki najprihvatljivije alternativno rješenje s 57 % manje emisija od dizelskog u periodu 30 godina, uz tek 3 % veće troškove. Unatoč tome, zbog velikih godišnjih operativnih troškova, i eventualnog problema masa i smještaje baterije, metanolski pogon se ističe kao najprikladniji. Uzrokuje 36 % manje emisija od dizela za 5 % veće cjeloživotne troškove, s dobrim profilom godišnjih troškova. Rezultati dobiveni iz provedenih analiza trebali bi biti samo smjernica za daljnje osnivanje brodskog energetskog sustava, s detaljnijim uvidom u konstrukciju i formu broda, režime plovidbe i lučke infrastrukture.In this thesis, the Croatian fleet of small coastal fishing vessels was analysed. The annual carbon footprint of the Croatian fleet of vessels up to 12 meters in length was calculated. Using the example of one vessel, Life Cycle Assessment (LCA) and Life Cycle Cost Assessment (LCCA) were conducted for a lifespan of 30 years. The solutions considered were a fully electric vessel, a hybrid electric vessel, a vessel powered by Liquefied Natural Gas (LNG), biodiesel, and a vessel powered by methanol. The proposed solutions were then compared with the reference diesel engine. For a better understanding of the proposed solutions, investment return analyses and sensitivity analyses on fuel price changes were also conducted. According to current law, the carbon tax only covers ships over 5000 gross tonnage. Considering that the vessel is observed over a period of 30 years, during which the law may change, an LCCA analysis was also conducted in the case of the introduction of a carbon tax. The LCCA results show that the diesel vessel is the most cost-effective, but the other solutions deviate relatively little. The LCA indicates that a fully electric vessel is the most environmentally friendly alternative solution, with 57% fewer emissions than diesel over a period of 30 years, with only 3% higher costs. Despite this, due to high annual costs and potential issues with the weight and placement of the battery, methanol propulsion stands out as the most suitable. It causes 36% fewer emissions than diesel for 5% higher lifetime costs, with a good annual cost profile. The results obtained from the conducted analyses should serve as a guideline for the further establishment of the vessel's energy system, with a more detailed insight into the construction and form of the vessel, sailing regimes, and port infrastructure
Validation of MEKC-MS/MS method for determination of abemaciclib, palbociclib and ribociclib in blood plasma
No full textHR+/HER2- rak dojke jedan je od najčešćih tipova karcinoma u svijetu, za čije se liječenje koristi kombinacija inhibitora CDK4/6 s endokrinom terapijom. Abemaciklib, palbociklib i ribociklib, selektivni su i reverzibilni inhibitori o ciklinima ovisnih kinaza, CDK 4 i 6.
S obzirom na potrebu za istovremenim određivanjem ovih lijekova iz krvne plazme pacijentica, razvijena je metoda micelarne elektrokinetičke kromatografije spregnute s tandemskom spektrometrijom masa (MEKC-MS/MS). Kako bi se navedena metoda mogla implementirati u rutinske analize biokemijskih laboratorija i sa sobom donijeti prednosti visoke efektivnosti, selektivnosti i manjeg utroška materijala te omogućiti terapijsko praćenje inhibitora CDK4/6 s ciljem poboljšanja ishoda liječenja, bilo ju je potrebno validirati sukladno ICH M10 smjernicama za validaciju bioanalitičkih metoda.
Linearnost, točnost i preciznost metode su validirane za abemaciklib u kalibracijskom području 50-500 ng/mL, za palbociklib 30-300 ng/mL i za ribociklib 500-5000 ng/mL. Na visokoj i niskoj QC koncentraciji, validirani su parametri utjecaja matrice i stabilnost uzoraka u autosampleru za svaki od tri inhibitora CDK4/6. Zaključno s validacijom ovih parametara, pokazano je kako je metoda prikladna za svoju namjenu.HR+/HER- breast cancer is one of the most common types of carcinomas across the world, for which the therapy includes combination of CDK4/6 inhibitors with endocrine therapy. Abemaciclib, palbociclib and ribociclib are selective and reversible inhibitors of cyclin-dependent kinases, CDK 4 and 6.
Due to the need for simultaneous determination of these drugs from the blood plasma of patients, a method of micellar electrokinetic chromatography coupled with tandem mass spectrometry (MEKC-MS/MS) was developed. In order for the above method to be implemented in routine analyses in biochemical laboratories and to bring with it the advantages of higher effectiveness, selectivity and lower material consumption, while enabling therapeutic monitoring of CDK4/6 inhibitors with the aim of improving treatment outcomes, it was necessary to validate it in accordance with ICH M10 Guideline for the validation of bioanalytical methods.
Linearity, accuracy, and precision of the method were validated in the calibration range of 50-500 ng/mL for abemaciclib, 30-300 ng/mL for palbociclib and 500-5000 ng/mL for ribociclib. Validation parameters matrix effect and stability in autosampler were validated for all of the three CDK4/6 inhibitors on the high and low QC (Quality control) concentrations, respectively to the ICH M10 Guideline. In conclusion, with validation of these parameters, it was shown that the method is suitable for its purpose
RAZVOJ NETKANOG AGROTEKSTILA IZ PRIRODNIH I OBNOVLJIVIH IZVORA ZA PRIMJENU U MALČIRANJU
No full textOver the past decade, growing awareness of the environmental impact of consumer products has driven a shift toward sustainable materials. The trend extends to textiles, including agrotextiles, since agrotextiles are predominantly fossil-based and pose significant ecological challenges due to their disposal. The doctoral dissertation focuses on developing nonwoven fabrics made from natural and renewable sources for mulching applications. Nonwoven mulches are produced mechanically on the card and bonded by the needle-punching process. The dissertation is divided into two experiments. The first experiment evaluates the biodegradability, weed control and soil quality impact of nonwoven mulches made from viscose (CV), jute, hemp and polylactic acid (PLA) fibres, and mulch blends made from viscose (CV), jute and hemp fibres blended with PLA fibres in a ratio of 80:20 as a potential sustainable alternative to conventional low-density polyethylene (LDPE) agrofoil. The second experiment investigates the impact of the same nonwoven mulches on lettuce growth and yield, comparing them to a control field (bare soil) and conventional PE agrofoil. Field experiments revealed significant visual and morphological changes confirmed by SEM analysis and structural and mechanical changes in the nonwoven mulches during exposure due to field conditions. Field conditions during experiments affected the mass per unit area, thickness, air permeability, and tensile properties of mulches, where PLA mulches and mulch blends with PLA show superior stability over time. The molecular degradation of cellulose-based fibres was confirmed through FTIR and WAXD analyses. The PLA mulches demonstrated greater resilience to open field conditions. Nonwoven mulches enhance soil conditions by stabilising soil temperature and moisture, increasing organic carbon levels, and promoting microbial activity, often outperforming PE agrofoil. Weed suppression of nonwoven mulches was confirmed, where PLA-based mulches maintain effectiveness during an extended period of exposure, since the cellulose-based mulches, by degradation, lose weed suppression ability. In the lettuce cultivation, CV and jute blends with PLA outperformed PE agrofoil in productivity and nutrient content in lettuce and soil, highlighting their potential for sustainable agriculture. The results confirm that nonwoven mulches successfully suppress weed growth, are biodegradable without negatively impacting soil quality, and increase lettuce yield through their impact on the soil. This makes them a viable replacement for conventional PE agrofoil, where the possibility of their application significantly contributes to ecologically sustainable agricultural practices.Tijekom prošlog desetljeća, rastuća svjesnost o utjecaju proizvoda na okoliš potaknula je prelazak na održive proizvode. Trend obuhvaća i tekstil, uključujući agrotekstile, koji se uglavnom proizvode iz fosilnih izvora predstavljajući značajan ekološki izazov kod gospodarenja otpadom nakon upotrebe. Doktorska disertacija usmjerena je na razvoj netkanih tekstila proizvedenih od prirodnih vlakana te vlakana iz obnovljivih izvora za primjenu u malčiranju. Malčevi od netkanog tekstila proizvedeni su mehaničkim procesom na grebenaljci i učvršćeni postupkom iglanja. Disertacija je podijeljena u dva eksperimenta. Prvi eksperiment procjenjuje biorazgradljivost, učinak suzbijanja rasta korova i utjecaj na kvalitetu tla netkanih malčeva proizvedenih od vlakana viskoze (CV), jute, konoplje i polimliječne kiseline (PLA), te malčeva proizvedenih iz vlakana viskoze (CV), jute i konoplje u mješavini s PLA vlaknima u omjeru 80:20 kao potencijalnu održivu alternativu konvencionalnoj polietilenskoj agrofoliji niske gustoće (LDPE). Drugi eksperiment, istražuje utjecaj istih netkanih malčeva na rast salate i prinos, u usporedbi s kontrolnim poljem (neprekriveno tlo) i konvencionalnom PE agrofolijom. Istraživanja na polju otkrili su značajne vizualne, morfološke promjene potvrđene SEM analizom, te mehaničke i strukturne promjene netkanih malčeva tijekom izlaganja poljskim uvjetima. Uvjeti na polju tijekom istraživanja utjecali su na masu po jedinici površine, debljinu, propusnost zraka i vlačna svojstva netkanih malčeva. Malčevi proizvedeni iz PLA vlakana i u mješavinama s PLA vlaknima pokazuju bolju stabilnost tijekom vremena izlaganja. Molekularna razgradnja celuloznih vlakana potvrđena je FTIR i WAXD analizama, dok su PLA vlakna pokazala veću otpornost na vanjske uvjete polja. Netkani malčevi poboljšali su uvjete tla stabilizacijom temperature i vlage, povećanjem razine organskog ugljika i povećanjem aktivnosti mikroba u tlu, često nadmašujući PE agrofoliju. Potvrđeno je suzbijanje korova netkanim malčevima, pri čemu su malčevi proizvedeni u mješavinama s PLA vlaknima učinkovitiji tijekom duljeg razdoblja izloženosti, budući da malčevi na bazi celuloze razgradnjom gube sposobnost suzbijanja korova. Pri uzgoju salate,malčevi proizvedeni iz mješavina vlakana jute i PLA, te vlakana CV i PLA, nadmašili su PE agrofoliju u prinosu i sadržaju hranjivih tvari salate i tla, naglašavajući njihov potencijal za korištenje u održivoj poljoprivredi. Rezultati potvrđuju da netkani malčevi uspješno suzbijaju rast korova, biorazgradivi su bez negativnog utjecaja na kvalitetu tla i svojim djelovanjem na tlo povećvaju prinos salate. To ih čini održivom zamjenom konvencionalne PE agrofolije, a mogućnost njihove primjene značajnim doprinosom ekološki održivim poljoprivrednim praksama
Phytochemical composition and antioxidant capacity of selected flowering plants before and after in vitro digestion
No full textU posljednje vrijeme vlada veliki interes za istraživanjem cvjetnog materijala kao vrijednog izvora nutraceutika.
Obilje cvjetova zaostaje neiskorišteno u uzgojnom procesu industrijskih biljaka poput duhana i suncokreta, što nije u
skladu sa suvremenim načelima održive proizvodnje i kružne ekonomije. U okviru ovog rada provedeno je
spektrofotometrijsko određivanje sadržaja ukupnih polifenola, flavonoida, hidroksicimetnih kiselina, flavonola,
proantocijanidina i šećera u etanolnim ekstraktima latica duhana (Nicotiana tabacum L., Solanaceae) i crnog sljeza
(Malva sylvestris L., Malvaceae), tepala Heuffelova šafrana (Crocus heuffelianus Herb., Iridaceae) te jezičastih
cvjetova suncokreta (Helianthus annuus L., Asteraceae) i nevena (Calendula officinalis L., Asteraceae) prije i nakon
što su ekstrakti bili podvrgnuti modelu simulirane ljudske probave in vitro. Antioksidacijski kapacitet ekstrakata
ispitan je ABTS, DPPH i FRAP metodom. Ekstrakti Heuffelova šafrana imali su visoke udjele svih ispitivanih
fitokemijskih spojeva. Ekstrakti duhana i suncokreta odlikuju se visokim udjelima ukupnih polifenola i flavonoida, a
ekstrakti sljeza visokim udjelom proantocijanidina i ukupnih šećera. Većina fitokemijskih spojeva pokazuje dobru
stabilnost i visoku biodostupnost u uvjetima in vitro probave. Kod svih istraživanih matičnih ekstrakata izmjeren je
visoki antioksidacijski kapacitet u ABTS, DPPH i FRAP metodama, osim kod matičnog ekstrakta crnog sljeza, koji je
u DPPH metodi imao umjereni antioksidacijski kapacitet. Tijekom in vitro probave dolazi do smanjenja
antioksidacijskog kapaciteta ekstrakata. Ekstrakti duhana i suncokreta imali su dosljedno najveće antioksidacijske
kapacitete u svim provedenim testovima. Dobiveni rezultati upućuju na to da pripravljeni ekstrakti mogu poslužiti kao
potencijalni izvori bioaktivnih spojeva za funkcionalnu hranu, dodatke prehrani te kozmetičke i farmaceutske
primjene, što treba potvrditi daljnjim istraživanjima.Recently, there has been significant interest in researching floral material as a valuable source of nutraceuticals. An
abundance of floral biomass remains unused in the cultivation process of industrial plants such as tobacco and
sunflower, which is not in line with modern principles of sustainable production and circular economy. Within this
study, spectrophotometric determination was conducted to measure the content of total polyphenols, flavonoids,
hydroxycinnamic acids, flavonols, proanthocyanidins, and sugars in ethanolic extracts from the petals of tobacco
(Nicotiana tabacum L., Solanaceae) and black mallow (Malva sylvestris L., Malvaceae), tepals of Heuffel's saffron
(Crocus heuffelianus Herb., Iridaceae), and ray flowers of sunflower (Helianthus annuus L., Asteraceae) and marigold
(Calendula officinalis L., Asteraceae), both before and after the extracts were subjected to an in vitro model of
simulated human digestion. The antioxidant capacity of the extracts was evaluated using ABTS, DPPH, and FRAP
assays. Extracts from Heuffel's saffron exhibited high levels of all tested phytochemicals. Tobacco and sunflower
extracts were characterized by high levels of total polyphenols and flavonoids, while mallow extracts had high levels
of proanthocyanidins and total sugars. Most phytochemicals demonstrated good stability and high bioavailability
under in vitro digestion conditions. All investigated original extracts showed high antioxidant capacity in the ABTS,
DPPH, and FRAP assays, except for the original mallow extract, which exhibited moderate antioxidant capacity in the
DPPH assay. During in vitro digestion, a reduction in the antioxidant capacity of the extracts was observed.
Throughout all assays, tobacco and sunflower extracts consistently exhibited the highest antioxidant capacities. The
results suggest that the prepared extracts could serve as potential sources of bioactive compounds for functional foods,
dietary supplements, as well as cosmetic and pharmaceutical applications, which should be confirmed by further
research
Design of metal-free catalysts for CO2 reduction
No full textPrateći sve intenzivnije napore znanstvene zajednice u razvoju nemetalnih katalizatora za redukciju ugljikova dioksida (CO2), potaknute rastućim izazovima klimatskih promjena, ovaj rad istražuje potencijal fosfina kao donora hidrida i istodobno kao katalizatora za reakciju redukcije CO2 u mravlju kiselinu. Koristeći računalne kvantno-kemijske metode (DFT), ispitana je sposobnost doniranja hidrida kod protoniranih difosfina supstituiranih elektron-donorskim skupinama: tris(dimetilamino)fosfazenilnom, tris(pirolidino)fosfazenilnom i tetrametilgvanidinskom. Ključan aspekt dizajna ovih difosfina je mogućnost formiranja dativne P–P veze nakon doniranja hidridnog iona, koja značajno pridonosi hidridnom karakteru i katalitičkom potencijalu spojeva. Ispitana je hidričnost ukupno 18 difosfina, a za dva od njih (spojevi 1aa i 4aa) izračunati su reakcijski putevi konverzije CO2 u mravlju kiselinu. Pri tome je utvrđeno da spoj 4aa posjeduje dobar potencijal za katalitičko djelovanje jer je cijeli reakcijski ciklus, uključujući i regeneraciju katalizatora, termodinamički i kinetički ostvariv. Ovim istraživanjem otvara se novi smjer u razvoju nemetalnih katalizatora temeljenih na fosfinima, koji su dosad bili slabo istraženi u kontekstu redukcije CO2.In response to the growing need for metal-free catalyst design for the reduction of carbon dioxide (CO₂), driven by the escalating impact of climate change, this study explores the potential of protonated phosphine compounds to act as both hydride donors and catalysts for reduction of CO2 to formic acid. Using computational quantum-chemical methods (DFT), the hydride-donating ability of protonated diphosphines substituted with electron-donating groups — tris(dimethylamino)phosphazenyl, tris(pyrrolidino)phosphazenyl, and tetramethylguanidino — was investigated. The design of diphosphines capable of forming a dative P–P bond upon hydride donation has proven crucial, as this interaction significantly enhances both the hydride-donating ability and the catalytic potential of these compounds. The hydricity of a total of 18 diphosphines was investigated, and for two of them (compounds 1aa and 4aa), reaction pathways for the conversion of CO2 to formic acid were calculated. It was found that compound 4aa has good potential for catalytic activity, as the entire reaction cycle, including catalyst regeneration, is both thermodynamically and kinetically feasible. This study opens a new direction in the development of non-metallic catalysts based on phosphines, which have so far been scarcely explored in the context of CO2 reduction