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    The effect of different inhalation therapies on mechanical ventilation-associated pneumonia in patients with COVID-19: a randomized controlled trial

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    Cilj istraživanja: Ova studija imala je za cilj istražiti učinke rutinske inhalacijske terapije na pneumoniju povezanu s ventilatorom (VAP) u mehanički ventiliranih bolesnika s koronavirusnom bolešću (COVID-19) uzrokovanog akutnog respiratornog distres sindroma (ARDS-a). Materijali i metode: Ovo randomizirano kontrolirano ispitivanje uključivalo je 175 odraslih bolesnika s COVID-19 koji su bili liječeni mehaničkom ventilacijom u KBC-u Split između listopada 2020. i lipnja 2021. Bolesnici su randomizirani i raspoređeni u kontrolnu skupinu (bez rutinske inhalacije) ili jednu od 3 intervencijske skupine (inhalacija N-acetilcisteina; 5% otopine natrijevog klorida; ili 8,4% natrijevog bikarbonata). Primarni ishod bila je incidencija VAP-a, dok su sekundarni ishodi uključivali smrtnost od svih uzroka. Rezultati: Rutinska inhalacijska terapija nije imala utjecaja na incidenciju bakterijskog ili gljivičnog VAP-a niti na smrtnost od svih uzroka (P>0,05). Sekundarne analize otkrile su značajno smanjenje gram-pozitivnog i meticilin-rezistentnog Staphylococcus aureus (MRSA) VAP-a u terapijskim skupinama. Konkretno, skupina koja je primala bikarbonat imala je statistički značajno nižu incidenciju VAP-a gram-pozitivnih bakterija (4,8%), zatim skupina koja je primala N-acetilcistein (10,3%), skupina koja je primala 5% natrijev klorid (19,0%) i kontrolna skupina (34,6%; P=0,001). Ta je razlika bila uzrokovana nižom učestalošću MRSA VAP u skupini koja je primala bikarbonat (2,4%), zatim skupini koja je primala N-acetilcistein (7,7%), skupini koja je primala 5% natrijev klorid (14,3%) i kontrolnoj skupini (34,6%; P0.05). Secondary analyses revealed a significant reduction of Gram-positive and methicillin-resistant Staphylococcus aureus (MRSA) VAP in the treatment groups. Specifically, the bicarbonate group had a statistically significantly lower incidence of Gram-positive bacterial VAP (4.8%), followed by the N-acetylcysteine group (10.3%), 5% saline group (19.0%), and control group (34.6%; p=0.001). This difference was driven by a lower incidence of MRSA VAP in the bicarbonate group (2.4%), followed by the N acetylcysteine group (7.7%), 5% saline group (14.3%), and control group (34.6%; p <0.001). Longer duration of ventilator therapy was the only significant, independent predictor of any bacterial or fungal VAP in the multivariate analysis (aOR 1.14, 95% CI 1.01–1.29, p=0.038 and aOR 1.05, 95% CI 1.01–1.10, p=0.028, respectively). Conclusions: In conclusion, inhalation therapy had no effect on the overall VAP incidence or all-cause mortality. Further studies should explore the secondary findings of this study such as the reduction of Gram-positive or MRSA-caused VAP in treated patients

    Influence of the relevant parameters in scour process around bridge piers protected by the riprap sloping structure

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    Stupovi mostova u rijekama izloženi su lokalnoj eroziji uslijed kompleksne interakcije trodimenzionalnog polja tečenja i riječnog sedimenta. Najčešća metoda sanacije i prevencije od podlokavanja je riprap – zaštita od kamenog nabačaja. Iako riprap štiti stup mosta, podlokavanje se nastavlja na nizvodnoj dionici korita i stvara se pojava odbačene kaverne. Trenutno stanje znanja o fenomenu podlokavanja oko stupa mosta već zaštićenog riprapom dosad nije istraženo. Cilj ovog istraživanja je prikupiti bazu utjecajnih varijabli kojima će se iznaći zavisnost između ravnotežnog stanja odbačene kaverne i utjecajnih varijabli. Uspostavom fizičkog i numeričkog modela provedeni su eksperimenti i simulacije na karakterističnoj geometriji riprap zaštite i rasponu rubnih uvjeta u kojima se stupovi zaštićeni riprapom mogu naći u prirodnom okruženju. Temeljna pretpostavka ovog istraživanja je da se morfodinamički procesi podlokavanja oko riprap zaštite mogu bolje opisati sa lokalno izmjerenim hidrodinamičkim karakteristikama u odnosu na uobičajeno korištene globalno usrednjene varijable. U ovom istraživanju koristile su se dvije lokacije za prikupljanje lokalnih hidrodinamičkih varijabli: pridneno područje iznad odbačene kaverne i područje uz stijenku stupa iznad riprap zaštite. Lokacije lokalnih varijabli predstavljaju područja na kojima je moguće kontinuirano pratiti hidrodinamičke varijable u prirodi. Primjenom višestruke nelinearne regresije izvedene su empirijske jednadžbe za procjenu ravnotežnog stanja odbačenih kaverni. Analizom izvedenih jednadžbi pokazano je da se lokalnim varijablama značajno poboljšava predikcija nizvodnih morfodinamičkih procesa u odnosu na globalne varijable. Ovom disertacijom određene su najutjecajnije karakteristike lokalnog polja tečenja kojima se može pouzdano procijeniti dubina odbačene kaverne formirane uz riprap zaštitu stupa mosta.The turbulent flow field in rivers induces local scour around bridge piers, which affects thesafety of the bridge by undermining the foundations and altering the effects of the flow on thestructure. A typical scour protection measure for bridges built in large rivers is riprap slopingstructure, formed by a launchable stone conically shaped around the pier. Although the riprap sloping structure effectively protects the pier from scour, its considerable dimensions additionally obstruct the flow in the bridge opening and induce scouring downstream of the bridge profile. Shifting the inception point of erosion downstream of the pier means that the position and extent of a scour hole formed in the interaction of the oncoming flow and the coarse riprap are unknown. The deflected scour hole therefore poses an indirect threat not only to the bridge, but also to the infrastructure and river training structures downstream of the bridge as well. Numerous studies have been conducted to investigate the scour process around bridge piers in order to optimize bridge design. However, research on scour evolution around bridges protected with riprap throughout their lifespan, considering continuous changes in flow environment and bed development, are rare. Aiming to bridge the existing knowledge gap in scour development next to the piers protected with riprap sloping structure, this dissertation provides a detailed analysis of the local flow field and scour formation next to the riprap sloping structure under different flow scenarios. Scour depth is usually described as a function of various global flow parameters: mean velocity, mean depth, bed shear stress, etc. However, this approach neglects the local hydrodynamic processes resulting from the complex interaction between the irregularly shaped riprap and the turbulent nature of a river flow. The flow hydraulics of bridges that are protected by a riprapsloping structure is complex, characterized by a flow around the structure during water levels below the top of the riprap, and overtopping flow during high flow events when the structure is completely submerged. The main assumption behind this research is that the scour processes around the riprap sloping structure can be estimated more accurately if local flow parameters are used instead of the commonly used globally averaged values. The flow parameters defined as local in this dissertation are the ones measured in the near-bed surface layer above the scour hole and adjacent to the bridge pier above the riprap crest. The locations where the local parameters were measured are based on practical considerations of monitoring techniques in the field application. The aim of the dissertation is to compare the accuracy of scour hole depth estimation calculated with empirical equations using the relevant global and local parameters as input. The main assumption of the research is that scour hole depth is influenced by the local parameters, and that understanding of local flow environment can help to improve the accuracy of equilibrium scour depth estimation. To determine the most relevant parameters that influence scour next to the riprap sloping structure, the hydrodynamic parameters were measured on a physical model and simulated using the Flow-3D numerical model with identical geometry and flow environment. The physical model was set-up in a hydraulic channel with a sand bed and characteristic riprap sloping structure geometry. Clear-water scour experiments were conducted for a range of flow conditions representative for submerged and non-submerged conditions. The boundary conditions were adjusted to reflect low to mean water levels when the riprap sloping structure is not submerged, and high flow levels when the top of the riprap is submerged 2 times its height. A total of twelve experimental runs were carried out: seven clear-water cases (flow rates ranging from 20 l/s to 32 l/s), two marginal cases representing the no-scour and live-bed limits (18 l/s and 34 l/s), and three synthetical cases where flow velocity was kept constant (28.2 l/s, 11.1 l/s, and 9.1 l/s). Each experiment was carried out continuously for 30 hours to reach an equilibrium scour state, after which the bathymetry of the scoured bed was measured using an optical laser scanner. The instantaneous velocities in the near-bed surface layer above the scour hole were measured with the Acoustic Doppler Velocimeter Profiler (ADVP). A grid of 15 measurement points was defined, covering the extent of the area where scour hole was developing. Second order turbulence transport equations were calculated from the instantaneous velocity measurements to determine the value of the local Reynolds shear stress and turbulent kinetic energy. Based on the collected database combining the experimental and simulated data, regression models are used to evaluate direct relationships between the relevant hydrodynamic variables(flow depth, flow velocity, turbulent kinetic energy, and Reynolds shear stress) and scour depth. The coefficients of determination (R²) were used as a measure to quantify how well the regression model fits the data. The analysis was performed individually for the measurement point closest to the maximum scour depth and combined for multiple points spanning over the entire scour hole perimeter to determine whether the prediction of scour is more reliable when the hydrodynamic parameters are measured at a one point of maximum scour depth or averaged over the larger area. The coefficients of determination were calculated for all measurement points and for all experiments to determine the strongest dependence between scour depth and area size for the averaging the hydrodynamic parameters. The area that showed the strongest relationship with scour depth is the entire area within the scour perimeter, which consisted of 9 measurement points. The strongest individual relationship with scour hole depth is observed for the turbulent kinetic energy, followed by the Reynolds shear stress in the near-bed surface layer above the scour hole, 0.9436 and 0.9255, respectively. The lowest R² value was obtained for the local shear stress adjacent to the bridge pier above the riprap crest (0.5524). In general, the global parameters showed a weaker dependence on scour depth compared to the local parameters, as R² for mean flow depth, mean flow velocity and bed shear stress yielded lower values of 0.8964, 0.8855 and 0.8845, respectively. For the analysis of the empirical equations, the relevant parameters were categorized into three groups: global parameters averaged over the entire cross section, local parameters adjacent to the bridge pier above the riprap, and local parameters in the near-bed surface layer above the scour hole. The dimensional analysis is performed to ensure the dimensional homogeneity of the relevant parameters. Dimensional analysis is used to determine a functional dependency between scour as a response variable and the relevant parameters arranged in non-dimensional functional groups. As a result, three empirical equations were derived based on a multiple non- linear regression analysis. The performance of the derived equations was evaluated by plotting the predicted vs observed values against the line of best fit. The equation developed based on local parameters collected in the near-bed surface layer above the scour hole showed the best performance (R² = 0.9225), followed by the equation derived from parameters collected adjacent to the bridge pier above the riprap (R² = 0.9073), while the lowest performance was observed for the equation derived for global parameters (R² = 0.8760). Deriving an additional equation by modifying the best-fit equation to include the turbulent kinetic energy in the near- bed surface layer above the scour hole showed a significant improvement (R² = 0.9666) in predicting scour depth. When post-scour bed development is observed, its pattern shows a significant development of bedforms downstream of the scour hole for all clear-water experiments. The bedforms develop in the entire downstream area, beyond the direct influence of riprap on the flow field. This indicates that the scour hole, once it develops, initiates bed deformation that interacts with the flow field and influences further scour development. This phenomenon confirms the importance of considering local fluctuations as the main cause of local scour around riprap sloping structure. In this dissertation, two hypotheses were proposed to investigate the phenomenon of scour around bridge piers protected with a riprap sloping structure. The first hypothesis states that the equilibrium scour depth is influenced by the flow regime over the riprap structure. The first hypothesis is confirmed through the validation of the strong dependence of the local parameters above the riprap structure adjacent to the bridge pier (R² = 0.9073) compared to the other empirical equations. The second hypothesis states that the maximum scour depth does not correspond to the maximum flow depth. The second hypothesis is confirmed through the validation, in which the scour hole reached a larger extent during low flows, where the overflowing effect above the riprap is absent, compared to the experiments at high flow, when the water level is above the riprap, while at the same time the mean flow approach velocity was kept constant. This research identified the most relevant hydrodynamic parameters needed to accurately estimate the scour hole depth developing next to the riprap sloping structure and thus improving the understanding of the scour process. The empirical equations demonstrate a significant improvement in the prediction of downstream morphodynamic processes when local parameters are considered, compared to the traditional approach that considers global parameters. The dominant influence of the local flow field above the scour hole on the morphodynamic process emphasizes the importance of monitoring local parameters in real time to support the decision-making process in bridge management systems

    Tumor budding and microsatellite instability in patients with sporadic colon and rectal cancer stage II

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    Bolesnici s kolorektalnim karcinomom stadija II predstavljaju skup biološki dosta različitih tumora različitog preživljenja unatoč homogenosti klasifikacije stadija II. Razvojem molekularne biologije i histopatologije javlja se potreba bolje kategorizacije s ciljem prepoznavanja karcinoma s većim rizikom diseminacije. U provedenoj studiji retrospektivno je analizirano 89 bolesnika s kolorektalnim karcinomom stadija II gdje su uz standardne sastavnice patohistološkog nalaza za kolorektalni karcinom određivani mikrosatelitna nestabilnost i tumorsko pupanje na standardnim hemalaun-eozinskim preparatima. Dobiveni podaci korišteni su za analizu preživljenja, i to odvojeno za endoskopske biopsije i resektate, uporabom algoritma rekurzivnoga particioniranja zvanog rpart. Iz podataka endoskopske biopsije, rpart algoritam smatra da najveći informacijski značaj imaju tumorsko pupanje, vaskularna invazija te dob bolesnika. Rpart algoritam iz podataka resektata određuje da najveći informacijski značaj imaju broj pregledanih limfnih čvorova, tumorsko pupanje te vaskularna invazija. U ovom radu rpart algoritam nije prepoznao mikrosatelitnu nestabilnost kao prognostički čimbenik na endoskopskoj biopsiji ni resektatu. Važno je istaći da uz biološke karakteristike tumora osnovnu prognostičku značajku kolorektalnog karcinoma stadija II čini kvaliteta izvedenog kirurškog zahvata te samog patohistološkog nalaza koja se očituje prvenstveno u broju pregledanih limfnih čvorova. Rezultati ovog rada upućuju na to da uz mikrosatelitnu nestabilnost tumorsko pupanje treba postati sastavni dio patohistološkog nalaza kolorektalnog karcinoma.Colorectal cancer stage II represent a set of biologically quite different tumors with different survival despite the homogeneity of the stage II classification. The study retrospectively analyzed 89 patients with colorectal cancer stage II, where in addition to the standard components of the pathohistological findings for colorectal cancer, MSI and tumor budding were determined. The data obtained were used for survival analysis, for endoscopic biopsies and resects. From endoscopic biopsy data, the rpart algorithm considers that tumor budding, vascular invasion, and age of patients are of the greatest informational importance. The rpart algorithm from the resect data determines that the number of examined lymph nodes, tumor budding and vascular invasion are of the greatest informational importance. In this paper, the rpart algorithm did not recognize microsatellite instability as a prognostic factor. It is important to point out that in addition to the biological characteristics of the tumor, the basic prognostic feature of stage II colorectal cancer is the quality of the performed surgery and the pathohistological findings, manifested primarily in the number of examined lymph nodes. The results suggest that in addition to microsatellite instability, tumor budding should become an integral part of the pathohistological findings of colorectal cancer

    The effects of salt intake on vascular function in pregnant women in the third trimester of pregnancy

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    Cilj istraživanja: Cilj istraživanja bio je ispitati utjecaj unosa soli hranom tijekom normalne trudnoće na maternalnu mikrovaskularnu i makrovaskularnu reaktivnost ovisnu o endotelu, razinu oksidativnog stresa, indekse fetoplacentne vaskularne funkcije, aktivnost renin-angiotenzinaldosteronskog sustava, ravnotežu placentnih proangiogenih i antiangiogenih čimbenika te biljege pregradnje posteljice. Nacrt studije: Ovo istraživanje ustrojeno je kao presječna opservacijska studija u kojoj su svim ispitanicima uzeti podatci, uzorkovanja i izvršena mjerenja u dvije vremenske točke. Ispitanici i metode: Na temelju 24-satne natrijureze trudnice (37 – 40 tjedana trudnoće) podijeljene su u tri skupine: normalni unos soli (NS; < 5,75 g/dan, N = 12), velik unos soli (HS; 5,75 – 10,25 g/dan, N = 36) i vrlo velik unos soli (VHS; > 10,25 g/dan, N = 17). Svim ispitanicama izmjerena je mikrovaskularna reaktivnost kože podlaktice u odgovoru na vaskularnu okluziju, lokalno zagrijavanje (LTH) i iontoforezu acetilkolina (AChID), kao i protokom posredovana dilatacija (FMD) brahijalne arterije. Izmjereni su sljedeći biljezi endotelne funkcije i oksidativnog stresa: serumska koncentracija dušikovog oksida (NO), endokana, 8-izo-prostaglandina F2a (8-izoPGF2a), reaktivne supstance tiobarbiturne kiseline (TBARS) i sposobnost redukcije željeza u plazmi. Izmjereni su ultrazvučni pokazatelji fetoplacentne funkcije, aktivnost renina u plazmi, koncentracija aldosterona, topljive fms-u slične tirozin kinaze-1 (sFlt-1) i posteljičnog čimbenika rasta (PlGF) u serumu te koncentracija vaskularnog endotelnog čimbenika rasta C (VEGF-C) i matriks metaloproteinaze 9 (MMP-9) u tkivu posteljice. Rezultati: FMD brahijalne arterije, mikrovaskularni AChID i LTH značajno su smanjeni u skupini VHS u usporedbi sa skupinom NS, a i LTH u skupini NS u usporedbi sa skupinom HS. NO je bio značajno smanjen u skupinama HS i VHS u usporedbi sa skupinom NS. Endokan, 8-izo-PGF2a i TBARS bili su značajno povećani u skupini VHS u usporedbi sa skupinom NS. Indeks pulsatilnosti fetalne srednje cerebralne arterije (MCA) bio je značajno smanjen u skupinama HS i VHS u usporedbi sa skupinom NS. Koncentracija aldosterona pokazala je tendenciju porasta s unosom soli, a omjer sFlt-1/PlGF bio je značajno smanjen u skupini VHS u usporedbi sa skupinom NS. Koncentracija VEGF-C i MMP-9 nije se razlikovala među skupinama. 8. SAŽETAK 74 Zaključak: Velik unos soli hranom povezan je sa smanjenom vazodilatacijom ovisnom o endotelu posredovanom NO-om u perifernoj mikrocirkulaciji i makrocirkulaciji zdravih trudnica te povećanim oksidativnim stresom. Nadalje velik unos soli povezan je sa smanjenom pulsatilnošću fetalne MCA, ali i povišenom koncentracijom aldosterona, smanjenim (povoljnijim) omjerom sFlt1/PlGF i nepromijenjenim biljezima pregradnje posteljice.Title: The effects of salt intake on vascular function in pregnant women in the third trimester of pregnancy Objectives: The aim of the study was to investigate the effects of dietary salt intake during normal pregnancy on maternal endothelium-dependent micro- and macrovascular reactivity, degree of oxidative stress, indices of fetoplacental vascular function, activity of the renin-angiotensinaldosterone system (RAAS), balance of placental pro- and antiangiogenic factors, and biomarkers of placental remodeling. Study design: This study was designed as a cross-sectional observational study in which data, samples and measurements were taken from all respondents at two time points. Participants and Methods: Based on 24-hour natriuresis, pregnant women (37–40 weeks gestation) were divided into three groups: normal salt intake (NS; <5.75 g/day, N=12), high salt intake (HS; 5.75 – 10.25 g/day N=36), and very high salt intake (VHS; >10.25 g/day, N=17). In all subjects, microvascular reactivity of the forearm skin was measured in response to vascular occlusion, local heating (LTH) and acetylcholine iontophoresis (AChID), as well as flow-mediated dilation (FMD) of the brachial artery. The following biomarkers of endothelial function and oxidative stress were measured: serum concentrations of nitric oxide (NO), endocan, 8-isoprostaglandin F2a (8-iso-PGF2a), thiobarbituric acid reactive substances (TBARS) and the ferric reducing ability of plasma. Ultrasound indices of fetoplacental function, plasma renin activity, aldosterone concentration, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured in serum, and vascular endothelial growth factor C (VEGF-C) and matrix metalloproteinase 9 (MMP-9) concentration were measured in placental tissue. Results: Brachial artery FMD, microvascular AChID and LTH were significantly reduced in the VHS group compared to the NS group, and LTH was also significantly reduced in the NS group compared to the HS group. NO was significantly reduced in both the HS and VHS groups compared to the NS group. Endocan, 8-iso-PGF2a and TBARS were significantly increased in the VHS group compared to the NS group. Fetal middle cerebral artery (MCA) pulsatility index was significantly reduced in the HS and VHS groups compared to the NS group. Aldosterone concentration showed a tendency to increase with salt intake, and the sFlt-1/PlGF ratio was significantly reduced in the 9. SUMMARY 76 VHS group compared to the NS group. The concentration of VEGF-C and MMP-9 did not differ between the observed groups. Conclusions: High dietary salt intake is associated with reduced endothelium-dependent NOmediated vasodilatation in the peripheral microcirculation and macrocirculation of healthy pregnant women and increased oxidative stress. Furthermore, high salt intake is associated with decreased fetal MCA pulsatility, but also with increased aldosterone concentration, decreased (more favorable) sFlt-1/PlGF ratio and unchanged markers of placental remodeling

    The Expression of mRNA HIF1A and GLUT1, HIF-1α and VEGF-A proteins in renal cancers

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    Unutar relativno rijetkog kliničkog entiteta raka bubrega, izdvaja se više patoloških dijagnoza, među kojima po učestalosti dominiraju svijetlostanični, papilarni, i kromofobni karcinom. Nova klasifikacija raka bubrega poseban naglasak stavila na razlikovanje rijetkih podtipova raka bubrega na osnovu molekularnog profiliranja. Molekularni mehanizam najčešćeg podtipa raka bubrega, svijetlostaničnog, počiva na disregulaciji VHL gena i njegovog ciljnog proteina pVHL, čija je uloga razradnja HIF-1α. U stanju hipoksije, HIF1α se stabilizira, inhibira se njegova degradacija što dovodi do njegovog nakupljanja unutar stanica i njegove aktivacije. Stabilizirani i akumulirani HIF-1α dovodi do aktiviranja transkripcije VEGF gena, ključnog gena za angiogenezu te GLUT1, proteina za transport glukoze. Okoliš brzorastućeg tumora u stanju je relativne hipoksije, stoga je neoangiogeneza uvjet za podržavanje tumorskog rasta, prilagodbu tumora i metaboličku promjenu u aerobnu glikolizu. Klinički prognostički alati ne uzimaju u obzir niti histološki tip, niti patomorfološke osobine tumora, a terapijske mogućnosti u liječenju raka bubrega donedavno su bile ograničene na peroralnu terapiju usmjerenu na tirozin -kinaze receptora za čimbenik rasta vaskularnog endotela ili na bevacuzimab, monoklonalno protutijelo usmjereno na čimbenik rasta vaskularnog endotela, obzirom da je VEGF bio jedina prepoznata terapijska meta, a specifično onkološko liječenje rezervirano samo za metastatske stadije. Nove imunoterapijske opcije temelje se na PD-1 ili PD L1 izražaju unutar tumora ili tumorskog mikrookoliša. U ovom istraživanju prikazan je izražaj HIF-1A gena i njegovog ciljnog proteina HIF-1α, te njegovih nizvodnih meta -VEGF-a i GLUT1 u tri najčešća tipa karcinoma bubrega. Značajno veća nuklearni izražaj HIF-1α uočena je u pRCC u usporedbi s ccRCC, dok nije bilo značajne razlike u izražaju proteina VEGF-A između analiziranih histoloških podtipova RCC. GLUT1 je više izražen kod ccRCC nego kod pRCC i chRCC, ali nije bilo razlike u izražaju GLUT1 ovisno o gradusu tumora RCC-a, niti veličine tumora. Kvantitativna lančana reakcija polimeraze reverzne transkripcije za HIF1A nije pokazala statističku razliku između histoloških tipova. Većina do sada objavljenih studija u obzir je uzimala samo svijetlostanični tip raka bubrega, u ovoj studiji obuhvaćeni su papilarni i kromofobni rak bubrega. Različiti rezultati analiziranih parametara dokazuju razlike onkogeneze među različitim tipovima raka bubrega. Prospektivna studija koja bi kombinirala i onkološke ishode u rezultatima, dodatno može pojasniti značaj analiziranih biljega u kliničkoj praksi među različitim tipovima raka bubrega.Within the relatively rare clinical entity of kidney cancer, several pathological diagnoses can be distinguished, among which clear cell, papillary, and chromophobe carcinoma dominate in terms of frequency. The new classification of kidney cancer places special emphasis on distinguishing rare subtypes of kidney cancer based on molecular profiling. The molecular mechanism of the most common subtype of kidney cancer, clear cell, rests on the dysregulation of the VHL gene and its target protein pVHL, whose role is the production of HIF-1α. In hypoxic conditions, HIF1α is stabilized, its degradation is inhibited, which leads to its accumulation inside cells and its activation. Stabilized and accumulated HIF-1α leads to the activation of transcription of the VEGF gene, a key gene for angiogenesis, and GLUT1, a protein for glucose transport. The environment of a fast-growing tumor is in a state of relative hypoxia, therefore neoangiogenesis is a condition for supporting tumor growth, tumor adaptation and metabolic change to aerobic glycolysis. Clinical prognostic tools do not take into account either the histological type or the pathomorphological features of the tumor, and therapeutic options in the treatment of kidney cancer were until recently limited to oral therapy directed at vascular endothelial growth factor receptor tyrosine kinases or at bevacuzimab, a monoclonal antibody directed at the factor growth of the vascular endothelium, given that VEGF was the only recognized therapeutic target, and specific oncological treatment was reserved only for metastatic stages. New immunotherapy options are based on the expression of PD-1 receptor or PD-L1 expression within the tumor or tumor microenvironment. In this study, the expression of the HIF-1A gene and its target protein HIF-1α, as well as its downstream targets - VEGF and GLUT1, in the three most common types of kidney cancer was shown. A significantly higher nuclear expression of HIF-1α was observed in pRCC compared to ccRCC, while there was no significant difference in VEGF-A protein expression between the analyzed histological subtypes of RCC. GLUT1 is more expressed in ccRCC than in pRCC and chRCC, but there was no difference in GLUT1 expression depending on the grade of the RCC tumor, nor the size of the tumor. No statistical difference ih HIF1A expression between histological types using quantitative reverse transcription polymerase chain reaction was shown. The different results of the analyzed parameters prove the differences of oncogenesis among different subtypes of kidney cancer. Most of the studies published so far considered only the clear cell type of kidney cancer, this study included papillary and chromophobe kidney cancer. The different results of the analyzed parameters prove the differences of oncogenesis among different types of kidney cancer. A prospective study that would combine oncological outcomes in the results can additionally clarify the significance of the analyzed markers in clinical practice among different types of kidney cancer

    Empirical and Transcendental Correlation Between World and Consciousness : A Phenomenological Contribution to Cognitive Science

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    Fundamentalno istraživanje u radu svjesni um i svijet razmatra kao sukonstitutivne, nerazdvojne sastavnice kognitivnog sustava, kako na empirijskoj razini dostupnoj pozitivnoj znanosti, tako i na transcendentalnoj razini koju otkrivaju filozofijske analize. Ono je potaknuto, s jedne strane, prigovorima upućenim kognitivnoj znanosti da je zanemarila ulogu svijesti i svijeta u proučavanju uma kao višestruko ostvarivog kompjutacijsko reprezentacijskog sustava, a s druge fenomenologijskim deskripcijama jedinstvene strukture života svjesnog svijeta te našeg biti-u-svijetu nakon provedbe transcendentalne, odnosno ontologijske redukcije, kojima pak manjka empirijska verifikacija. Nakon komparativnih analiza različitih pristupa u kognitivnoj znanosti, izvršenih u prvom, drugom i trećem dijelu disertacije, autor se u daljnjem konceptualnom istraživanju vodi definicijom kognicije kao sposobnosti snalaženja živih bića u svijetu koje rezultira novim a uvjetovano je prethodnim znanjem i vještinama. Drugim riječima, u stalnoj interakciji organizma i njegove okoline razvijaju se spoznaje i vještine, koje se onda primjenjuju na novonastale situacije. Ova interakcija, koja uvjetuje pojavu kognicije, može se razložiti na različite ali međusobno povezane procese metabolizma, homeostaze, reprodukcije, društvenog ponašanja, autonomnog djelovanja, osmišljavanja svijeta i dvostrane prilagodbe. Istraživanje stoga argumentira u prilog hipoteze da kognicija nije samo procesiranje informacija koje se osniva na nizu formalnih pravila i izvodi u slijedu koraka prema zadanim algoritmima, niti samo prepoznavanje obrazaca u propagaciji signala neuronskim mrežama, nego selektivna, regulativna, intencionalna, utjelovljena i situirana aktivnost autonomnih i društvenih bića usmjerenih na postizanje ciljeva, samoodržanje i prilagodbu. Prije uvođenja slojevite strukture svijeta u tematsko polje kognitivne znanosti, što je prema autoru izvorni doprinos fenomenologije, bilo je potrebno ukazati na različite aspekte svijesti koja ima kognitivni značaj pri integraciji informacija, globalnom dijeljenju rezultata modularnog procesiranja, snalaženju u novonastalim situacijama, konsolidaciji memorije, zamišljanju i planiranju, održavanju identiteta, uspostavljanju povoljnih okolišnih uvjeta, kontroli svrhovitog ponašanja, reagiranju na selektirane podražaje, tumačenju kauzalnih poveznica i uživljavanju u mentalna stanja drugih. Svijet, s druge strane, najprije kao prirodna i društvena okolina, zajedno s nasljednim genetičkim programom razvoja organizma, formira kapacitete kognitivnog agenta, određujući što će si i na koji način on predočiti, kako će to utjecati na njegovo ponašanje i povratno na uvjete u istoj toj okolini. Međutim, fenomenološke analize otkrile su da svijet kao univerzalni prostorno-vremenski horizont, pozadina koja definira predmetnost, temelj svih doksičkih postavljanja, dinamika poznatog i stranog, prisutnog i odsutnog, mreža značajnosti, motivacijski sklop i intersubjektivno formirana objektivna zbilja, nije nešto izvanjsko svjesnom umu, nego je život višerazinska korelacija subjekta i svijeta koja formira korelate kao dva suprotstavljena pola, ali dijelom istog dinamičkog procesa. Transcendentalna razina korelacije svijesti i svijeta u disertaciji predstavljena je kroz eidetske deskripcije fenomena koji jamče ovo dvostrano uvjetovanje, a to su konstitutivna intencionalnost, utjelovljenost, intersubjektivnost i povijesnost. Kao prafenomen ili temelj te povezanosti, tj. ono što transcendentalnu sferu drži na okupu, prepoznata je vremenitost, koja se očituje kao kognitivno, organsko, objektivno i ekstatično diferencirajuće vrijeme. Zaključno, empirijska i transcendentalna argumentacija u ovom interdisciplinarnom istraživanju zajedno potvrđuju da objektivno vrijedno znanje koje se može akumulirati, artikuirati, razvijati i prenositi nastaje iz dinamičke interakcije svjesnog, utjelovljenog subjekta i njegove složene i promjenjive prirodne, društvene i kulturne okoline, čime se ukazuje na nedostatnost kako tradicionalne paradigme uma kao računala tako i suvremenog neurocentrizma u kognitivnoj znanosti.Fundamental research in the present study considers the conscious mind and the world as co constitutive, inseparable components of the cognitive system, both on the empirical level accessible to positive science, and on the transcendental level revealed by philosophical analyses. It was motivated, on the one hand, by objections addressed to cognitive science that it neglected the cognitive role of consciousness and the environment by conceiving the mind as a multiply realizable computational-representational system and, on the other hand, by phenomenological descriptions of the unified structure of our world-conscious life and our being-in-the-world, after implementing the transcendental and ontological reductions respectively, which lack empirical verification. Following comparative analyses of different approaches in cognitive science, executed in the first, second and third part of the dissertation, further conceptual investigation is pursued according to the definition of cognition as the ability of living beings to cope with the world, which results in new but is conditioned by previous knowledge and skills. In other words, knowledge and skills are developed through constant interaction between an organism and its environment, and then applied to new situations. This interaction consists of different but interrelated processes of metabolism, homeostasis, reproduction, social behavior, autonomous action, bilateral adaptation, and making sense of the world. Presented research, therefore, supports the hypothesis that thinking is not only information processing based on a series of formal rules and performed in a sequence of steps according to given algorithms, nor is it just the recognition of patterns in the propagation of signals in a neural network, but a selective, regulative, intentional, embodied and situated activity of autonomous and social beings, aimed at achieving goals, self-preservation and adaptation. Before introducing the layered structure of the world into the thematic field of cognitive science, which is, according to the author, the original contribution of phenomenology, it was necessary to point out various aspects of consciousness having cognitive significance in the integration of information and global sharing of the results of modular processing, in coping with unfamiliar situations, consolidation of memory, imagining and planning, self-evidencing, establishing favorable environmental conditions, controlling purposeful behavior, reacting to selected stimuli, interpreting causal links, and immersing oneself in the mental states of others. The world, on the other hand, primarily as a natural and social environment, together with a hereditary genetic program, forms the capacities of a cognitive agent, determining how and what he will experience, how it will affect his behavior and, in turn, how will his actions change the conditions in that environment. However, phenomenological analyzes have revealed that the world as a universal spatio-temporal horizon, a background which defines objectivity, a permanent doxic basis, a dynamics of the known and the foreign, of the present and the absent, a network of significance, a motivational system and an intersubjectively formed reality, is not something external to the conscious mind. Life is a multilevel correlation of the subject and the world, forming the correlates as two opposing poles but parts of the same dynamic process. The transcendental level of the correlation is revealed in the present study through eidetic descriptions of phenomena that underlie this two-sided conditioning, namely constitutive intentionality, embodiment, intersubjectivity and historicity. Temporality, which manifests as cognitive, organic, objective and ecstatic-differentiating time, is now seen as the primal phenomenon or connective tissue that holds the transcendental sphere together. In conclusion, scientific and philosophical arguments in this interdisciplinary research confirm that objectively valuable knowledge that can be obtained, articulated, developed and transferred, arises from the dynamic interaction of conscious, embodied subject and its complex and changing natural, social and cultural environment, thus indicating the inadequacy of the traditional paradigm of the mind as a computer as well as contemporary neurocentrism in cognitive science

    Characterisation of the biological activity and formulation of encapsulated systems of phenylethanoid glycosides from mountain germander (Teucrium montanum L.)

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    U radu je provedena valorizacija polifenolnog ekstrakta trave ive (Teucrium montanum) karakterizacijom biološke aktivnosti i formuliranjem inkapsuliranih dozirnih sustava, inkorporiranih u formulacije funkcionalnih bombonskih proizvoda. U tu svrhu, implementirane su ekstrakcijske i inkapsulacijske tehnike te biološki test sustavi uz odgovarajuću analitičku metodologiju. U ekstraktima trave ive u najvećim udjelima identificirani su ehinakozid, teupoliozid, stahizozid A, poliumozid i verbaskozid. In vitro ispitivanjima na CAL-27, HepG2, Caco-2 i AGS staničnim linijama (0,025, 0,050, 0,150 i 0,500 mg ekstrakta mLˉ¹), utvrđen je statistički značajan (p<0,05), o koncentraciji ovisan antioksidacijski učinak, kao i genoprotektivan učinak koncentracije 0,500 mg mLˉ¹ na modelnom DNK plazmidu (p<0,05). Na in vivo modelu, utvrđen je statistički značajan (p<0,05) antioksidacijski učinak na stanice jetre, odnosno genoprotektivan učinak na stanice krvi pri svim koncentracijama ekstrakta (250, 500 i 1000 mg kgˉ¹). Inkapsulati formulirani sušenjem raspršivanjem na bazi arapske gume, guar gume i karboksimetil celuloze te nanovlakna dobivena elektroispredanjem na bazi pululana, kolagena, zeina i proteina konoplje, rezultirali su inkapsulacijskom učinkovitosti feniletanoidnih glikozida većom od 72 %, dok je dodatak karboksimetil celuloze, zeina i proteina konoplje usporio kinetiku otpuštanja polifenolnih spojeva u in vitro simuliranim uvjetima probave. Inkorporacijom inkapsulata, razvijeno je pet formulacija inovativnih veganskih žele proizvoda visoko obogaćenih feniletanoidnim glikozidima iz ekstrakta trave ive (Σ 1,2 mg gˉ¹) te poželjnih senzorskih i teksturalnih karakteristika.In this study, the valorization of mountain germander (MG) polyphenolic extract (Teucrium montanum) was carried out through the characterisation of biological activity and delivery systems formulation for the incorporation into functional jellies. For this purpose, extraction and encapsulation techniques, biological test systems with appropriate analytical methodology were used. Echinacoside, teupolioside, stachysoside A, poliumoside and verbascoside were identified in the highest yields. In vitro analysis on CAL-27, HepG2, Caco-2 and AGS (0.025, 0.050, 0.150 and 0.500 mg extract mLˉ¹) revealed a statistically significant (p<0.05), concentration-dependent antioxidant effect as well as genoprotective effect on DNA plasmid (0.500 mg mLˉ¹). In the in vivo model, a statistically significant (p<0.05) antioxidant effect on the liver, and genoprotective effect on blood, was observed for all extract concentrations (250, 500 and 1000 mg kgˉ¹). Spray-dried particles based on gum arabic, guar gum and carboxymethyl cellulose (CMC), and electrospun nanofibers with pullulan, collagen, zein (ZE) and hemp protein (HP), exhibited encapsulation efficiency of the phenylethanoid glycosides (PGs) over 72 %, while the addition of CMC, ZE and HP enabled sustained polyphenolic release kinetics under in vitro conditions. Incorporation of delivery system resulted in five innovative vegan jellies formulations, enriched with PGs from MG extract (Σ 1.2 mg gˉ¹) with desirable sensory and textural properties

    Ecological realism of James J. Gibson and sociocultural affordances

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    Ekološka teorija percepcije predstavila je revolucionarni preokret u tumačenju percepcije zauzimajući iznimno rijetko zastupanu poziciju direktnog realizma nasuprot dominirajuće pozicije indirektnog realizma za većinu teorija percepcije. Utemeljitelj ekološke teorije i ekološkog pristupa proučavanju percepcije, američki psiholog i filozof J. J. Gibson (1904- 1979), svoju je poziciju izričito vezao uz zdravorazumski ili naivni direktni realizam, a svoju teoriju percepcije smatrao je snažnom potporom direktnome realizmu. Prema ekološkoj teoriji percepcija je biološka i istraživačka aktivnost orijentirana na djelovanje, nerazdvojiva od propriocepcije, temeljena na podražajnim informacijama koje se nalaze u okruženju te je moguća zbog postojanja invarijanti u ambijentalnom optičkom poretku. Promatranjem okoline i kretanjem u njoj aktivno i pasivno pribavljamo podražaje te direktno prepoznajemo informacije putem mreže perceptivnih sustava koji su, zahvaljujući evolucijskom razvoju, sposobni izvući i registrirati sve relevantne informacije bez uključivanja viših kognitivnih funkcija u perceptivnom procesu. Percepcija je čin kojim jednostavno vidimo svijet oko sebe i koji nam omogućuje njegovu direktnu spoznaju. Prvi cilj ove disertacije bio je istražiti u kojem smislu Gibsonova izvorna ekološka teorija podupire direktni realizam budući da svojim središnjim konceptom afordancija kombinira objektivne i subjektivne elemente u percepciji te napušta standardne dualizme subjekt-objekt, pojedinac-okolina, unutarnje-vanjsko. Prema izvornoj definiciji afordancije su svojstva okoline u odnosu na životinju (jedinku, organizam) i njezino ponašanje, tj. aspekti okoline koji organizmu nude i omogućuju određeno djelovanje, a njihova aktualizacija objedinjuje svojstva okoline i svojstva promatrača te istovremeno odražava subjektivni i objektivni element u činu percepcije. Iako pojam afordancija na prvi pogled sugerira antirealizam, u kontekstu teorije o jednom sustavu (sustavu organizam-okolina), koncepta utjelovljene kognicije te teze o aktivnom subjektu, u potpunosti podržava direktnu percepciju i poziciju direktnog naivnoga realizma, što ne potvrđuje hipotezu prema kojoj Gibsonova izvorna ekološka teorija kombiniranjem objektivnih i subjektivnih elemenata u percepciji ne podupire koncepciju naivnoga direktnog realizma. Direktni realizam govori o tome što se događa na personalnoj razini gdje je važno da ishod (sadržaj) percepcije ne sadrži mentalne reprezentacije i ne ovisi o subjektu već samo o objektu, a percepcija može biti direktna i objektivna na personalnom i epistemološkom nivou. Tumačenjem percepcije primarno kao biološke aktivnosti s naglaskom 192 na aktivnog subjekta i njegovu istraživačku ulogu u činu percipiranja ekološka teorija ne ugrožava poziciju direktnog realizma budući da podrazumijeva aktivnost subjekta na subpersonalnoj razini koja nema epistemološki karakter. Drugi cilj bio je istražiti u kojoj mjeri Gibsonova koncepcija direktnog realizma i izvorni koncept afordancija preživljava proširenje na sociokulturne afordancije, budući da se Gibsonova definicija primarno odnosi na afordancije prirodnog okruženja i fizičke prirodne značajke okoline u odnosu na sve oblike života u okruženju. Proširenje koncepta afordancija na sociokulturno perceptivno okruženje sužava aspekt stvarnosti na ljudski oblik života, a sociokulturne afordancije definira kao stvarne mogućnosti koje društveno i kulturno okruženje nudi za razna ponašanja kojima izaziva različite kognitivne, emocionalne i motivacijske reakcije percipijenta. Kolektivna značenja i očekivanja tvore društveno i kulturno konstruirane mogućnosti za djelovanje i interakciju što su objektivne značajke okoline za sociokulturne afordancije. Subjektivni element odnosi se na sposobnost promatrača u poznavanju društvene i kulturne konvencionalnosti kao uvjet za aktivno odnošenje sa sociokulturnim afordancijama i prepoznavanje njihove korisnosti, važnosti i značenja. Unatoč argumentima kojima se želi opravdati realizam o afordancijama ne-prirodnog porijekla zaključuje se da sociokulturne afordancije predstavljaju problematičan moment za koncept direktnog realizma te da proširenje izvorne ekološke teorije percepcije i ekološkog realizma na sociokulturnu domenu stvarnosti nije u potpunosti u skladu sa svim zahtjevima direktnog realizma. Opravdanja za realizam sociokulturne stvarnosti i sociokulturnih afordancija, po pitanju zahtjeva ontoloških, epistemoloških i semantičkih teza, povezuju poziciju ekološkog realizma s postavkama evolucijskog realizma, naturalizma, društvenog naturalizma i entitetskog realizma, u dinamičku vrstu realizma koja integrira realističke i konstruktivističke elemente u procesu percepcije.The ecological theory of perception presented a revolutionary turn in the interpretation of perception, taking an extremely rarely represented position of direct realism against the dominant position of indirect realism favored by theories of perception. The founder of ecological theory and the ecological approach to perception, the American psychologist and philosopher J. J. Gibson (1904.−1979.), considered his theory of perception to be a strong support of common sense realism or naive direct realism. According to ecological theory, perception is a biological and action-oriented research activity, inseparable from proprioception and based on stimulus information found in the environment, while the existence of invariants in the ambient optical array makes perception possible. By observing the environment and moving in it we obtain stimuli actively and passively, and we directly recognize information through a network of perceptual systems that have evolved in such a way that they are capable of extracting all relevant information without involving higher cognitive functions in the perceptual process. Perception is the act by which we simply see the world around us and enables us to know it directly. The first goal of this dissertation was to explore in what sense Gibson's ecological theory supports direct naive realism, since, through its central concept of affordance, it combines objective and subjective elements in perception and abandons the standard dualisms subject−object, individual−environment, internal−external. Gibson defined affordances as a property of the environment in relation to the animal (individual, organism) and its behaviour, i.e. aspects of the environment that offer the organism a certain action. By combining the properties of the environment and the properties of the observer, the affordances simultaneously reflect the subjective and objective elements in the act of perception. Although, at first glance, the concept of affordances indicates anti-realism, in the context of the theory of the organism and the environment system, the concept of embodied cognition, and the thesis on the active subject, it actually supports direct perception and the direct naive realism. Direct realism talks about what happens on a personal level, where it is important that the outcome (content) of perception does not contain mental representations and does not depend on the subject but only on the object, and perception can be direct and objective on a personal and epistemological level. Explaining the perception primarily as a biological activity with an emphasis on the active subject in the act of perceiving, ecological theory does not threaten the position of direct 194 realism, since it implies the activity of the subject on a subpersonal level that does not have an epistemological character. Contrary to the hypothesis, it is concluded that Gibson's original ecological theory, by combining objective and subjective elements in perception, supports direct realism. Another goal was to investigate to what extent Gibson's conception of direct realism and his original concept of affordances can be applied to sociocultural affordances, since Gibson's definition primarily refers to affordances of natural and physical features of the environment in relation to all forms of life that inhabit it. The extension of the concept of affordances to the sociocultural perceptual environment narrows the aspect of reality to the human form of life, which defines sociocultural affordances as real opportunities that the social and cultural environment offers for various behaviours that cause cognitive, emotional and motivational reactions of the perceiver. Collective meanings and expectations form socially and culturally constructed opportunities for action and interaction represent objective features of the environment for sociocultural affordances. The subjective element refers to the observer's ability to recognize social and cultural conventionality as a condition for actively dealing with sociocultural affordances and recognizing their usefulness, importance, and meaning. Despite the arguments that try to justify realism about affordances of non-natural origin, the conclusion is that sociocultural affordances represent a problematic moment for the concept of direct realism and that the extension of the original ecological theory of perception to the sociocultural domain of reality is not fully in line with all the requirements of direct realism. Regarding the ontological, epistemological and semantic requirements, justifications for the realism of sociocultural reality and sociocultural affordances require connecting the position of ecological realism with evolutionary realism, naturalism, social naturalism and entity realism, into a dynamic type of realism that integrates realistic and constructivist elements in the process of perception

    Sport contact level and hygiene of athletes as predictors of Staphylococcus Aureus carriage rates before and during Covid-19 pandemic

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    Uvod: Ljudska koža normalno je naseljena raznim mikroorganizmima, no u određenim slučajevima oni mogu izazivati klinički manifestnu infekciju, pri čemu je – zbog svojeg patogenog potencijala – posebni interes u ovom istraživanju stavljen na bakteriju zlatni stafilokok (Staphylococcus aureus). Sportaši su populacija koja je, kao posljedica veće učestalosti ozljede kože i okolišnih uvjeta, pod povećanim rizikom od infekcije. Pandemija bolesti COVID-19 dovela je do velikih promjena u modalitetima treninga, kao i u higijensko-epidemiološkim postulatima. Glavni cilj istraživanja bio je utvrditi razliku u kliconoštvu zlatnim stafilokokom u odnosu na kontaktnost sporta i na pojavu pandemije bolesti COVID-19, kao i utvrditi postojanje razlike u pridržavanju higijensko-epidemioloških mjera prije i tijekom ove pandemije. Ciljevi i hipoteze: Glavni cilj ovog istraživanja bio je napraviti analizu stopa kolonizacije zlatnim stafilokokom kod sportaša u uvjetima prije i tijekom pandemije COVID-19 u odnosu na kontaktnost sporta kojim se bave i njihove higijensko-životne navike. Prvi podcilj bio je utvrditi postoji li korelacija kliconoštva zlatnim stafilokokom s higijenskim čimbenicima ispitivanim u anketi. Drugi podcilj bio je utvrditi eventualnu sezonsku razliku između kliconoša. H1: U kontaktnim sportovima bit će veći postotak ispitanika koloniziranih zlatnim stafilokokom. H2: Kliconoštvo zlatnim stafilokokom bit će učestalije u gornjem dišnom sustavu nego u aksilarnoj regiji. H3: Ordinalno stupnjevanje kliconoštva pozitivno će korelirati s neadekvatnim provođenjem postulata istraživanih anketom, kao i sa stupnjem kontaktnosti određenog sporta. H4: Utvrdit će se sezonska razlika te razlika između pretpandemijskog i pandemijskog razdoblja u kliconoštvu neovisno o kontaktnosti samog sporta. H5: Pridržavanje higijenskih postulata bit će izraženije u skupini ispitanika tijekom pandemije COVID-19. Materijali i metode: Provedena je presječna studija s prigodnim uzorkovanjem na 197 ispitanika – sportaša i sportašica koji prakticiraju kontaktne i nekontaktne sportove – u periodu prije i tijekom pandemije bolesti COVID-19. Ispitanici su podijeljeni u dvije glavne skupine prema dominantnoj kontaktnosti sporta koji prakticiraju, a dodatno s obzirom na razdoblje u vezi s pandemijom. Nakon potpisivanja informiranog pristanka i ispunjavanja ankete kojom su se utvrdile higijensko-epidemiološke navike ispitanika, sudionicima su učinjeni mikrobiološki brisevi predvorja nosa, ždrijela i aksile. Nakon provedene mikrobiološke analize uzoraka (koja je uključivala standardnu laboratorijsku obradu kao i napredne analitičke tehnologije poput MALDI-TOF), učinjena je statistička obrada podataka dobivenih anketom i uzorkovanjem. Provedene su metode deskriptivne i inferencijalne statistike, poput t-testa, Wilcoxonovog testa sume rangova, Leveneovog testa sume varijanci, Shapiro-Wilkovog testa odstupanja oblika opažene raspodjele od normalne, Brunner-Munzelove generalizirane verzije Wilcoxonovog testa, Fisherovog egzaktnog testa s ordinalnim skaliranjem, kao i druge statističke metode. Rezultati: Što se tiče kontaktnosti sporta, 49,75 % ispitanika prakticiralo je kontaktni, a 50,25 % nekontaktni sport. Zlatni stafilokok izoliran je kod 40,1 % svih ispitanika, a po kontaktnosti kod 58 % sportaša koji se bave kontaktnim i 42 % sportaša koji se bave nekontaktnim sportom (p = 0,071). Zlatni stafilokok je statistički značajno izoliran kod 48 % ukupnog broja muškaraca u odnosu na 27,6 % ukupnog broja žena (p = 0,0047). Ova je bakterija primarno izolirana iz predvorja nosa (64,56 % ukupnog broja kliconoša). Meticilin-rezistentni Staphylococcus aureus (MRSA) izoliran je kod 1,01 % ukupnog broja ispitanika. Osim zlatnog stafilokoka, izolirani su i drugi mikroorganizmi. Veći broj kolonija zlatnog stafilokoka porastao je iz uzoraka aksile sudionika koji su češće koristili teretanu te kod onih koji su rjeđe dezinficirali ruke, te iz uzoraka nosa ispitanika koji su češće dijelili zavojni materijal i kod onih koji su imali češća oštećenja kože. Kod ispitanika kod kojih je od mikroorganizama izoliran samo zlatni stafilokok, više je kolonizata zlatnog stafilokoka izolirano ljeti u odnosu na jesen. Također, u ovoj skupini ispitanika zamijećen je veći udio kolonizata zlatnog stafilokoka u aksili ispitanika kojima su brisevi uzeti tijekom pandemije. Rezultati istraživanja pokazali su da su ispitanici tijekom pandemije češće dezinficirali ruke i koristili zajedničku opremu, te da su rjeđe koristili teretanu. Zaključak: Istraživanjem su dokazane određene razlike u kliconoštvu zlatnim stafilokokom kod sportaša koji prakticiraju kontaktni u odnosu na one koji prakticiraju nekontaktni sport. Pronađene su i razlike u kliconoštvu u odnosu na higijensko-epidemiološke prakse, kao i na godišnja dobe te na period prije i tijekom pandemije COVID-19. Potvrđena je hipoteza da će kolonizacija zlatnim stafilokokom biti najučestalija u nosu. Dobiveni rezultati u skladu su s podacima iz svjetske literature, a poseban doprinos istraživanja je mogućnost promjena pristupa sportašima s obzirom na kontaktnost sporta temeljem dobivenih rezultata.Introduction: Human skin is normally inhabited by various microorganisms, yet in certain cases they can cause a clinically manifest infection. Due to its pathogenic potential, this thesis put the lens on Staphylococcus aureus (S. aureus). Athletes are a specific population that has an increased risk of infection due to higher frequency of skin injury and environmental conditions. The coronavirus disease 2019 (COVID-19) pandemic has led to major changes in training modalities, as well as in hygiene and epidemiological postulates. The main aim of the thesis was to determine the difference in S. aureus carriage rates in relation to contact/non-contact sports and the onset of the COVID-19 pandemic, as well as to determine the existence of significant differences in adhering to hygienic-epidemiological measures before and during the pandemic. Aims and hypotheses: The main aim of the thesis was to analyse S. aureus colonisation rates in athletes before and during the COVID-19 pandemic in relation to the level of contact pertinent for the sport they practice, as well as their hygienic lifestyle habits. There were two additional sub-aims: 1) to determine if there is a signficant correlation between S. aureus carriage and hygiene factors explored by the survey, and 2) to determine eventual seasonal difference between S. aureus carriers. H1: In contact sports, there will be a higher percentage of respondents colonized with S. aureus. H2: S. aureus infection will be more frequent in the upper respiratory system than in the axillary region. H3: Carriage rates (assessed on an ordinary scale) will positively correlate with the inadequate implementation of the hygiene postulates, as well as with the degree of contact of a particular sport. H4: There will be a significant seasonal difference and a difference between the pre-pandemic and pandemic periods in carriage rates, regardless of the level of contact of the sport itself. H5: Adherence to hygiene postulates will be higher in the group of respondents during the COVID-19 pandemic than before pandemic. Materials and methods: A cross-sectional study with convenient sampling approach was conducted on 197 respondents – athletes who practice contact and non-contact sports – in the period before and during the COVID-19 pandemic. The respondents were divided into two main groups according to the predominant type of contact of the sport they practice, and additionally with regard to the period related to the pandemic. After study participants signed the informed consent and filled out the survey which determined the hygienic-epidemiological habits, they were subjected to microbiological swabbing of the vestibule of the nose, pharynx and axilla. Upon analysing these samples (which included standard laboratory processing and advanced analytical technologies such as MALDI-TOF), statistical analysis was performed with the use of descriptive and inferential statistics methods – such as the t-test, the Wilcoxon rank sum test, the Levene test of the sum of variances, the Shapiro-Wilk test, the Brunner-Munzel generalized version of the Wilcoxon test, Fisher's exact test with ordinal scaling, as well as other statistical methods. Results: A total of 49.75% of respondents practiced contact sports, and 50.25% non-contact sports. The microorganism of interest, S. aureus, was isolated in 40.1% of all subjects – 58% of athletes who engage in contact sports and 42% of athletes who engage in non-contact sports (p = 0.071). S. aureus was isolated in 48% of men compared to 27.6% of women, which was a statistically significant difference (p = 0.0047). This bacterium was primarily isolated from the vestibule of the nose (i.e., 64.56% of the total number of carriers). Methicillin-resistant S. aureus (MRSA) was isolated in 1.01% of the total number of subjects. Apart from this bacterial agent, other microorganisms were also isolated. Furthermore, S. aureus was more frequently isolated from the axillae of participants who used the gym more often and those who disinfected their hands less often, as well as from the nasal samples of subjects who shared bandage material more often and those who presented with more frequent skin damage. In subjects who harboured only S. aureus as a potentially pathogenic microflora, higher carriage rates were seen in summer compared to autumn season. Also, in this group of subjects, a higher proportion of S. aureus carriage was observed in the axillae of subjects whose swabs were taken during the pandemic period. The results of the study showed that, during the COVID-19 pandemic, respondents disinfected their hands more often and used shared equipment, and that they used the gym less often. Conclusion: This thesis revealed certain differences in S. aureus carriage rates in athletes who practice contact sports in comparison to those who practice non-contact sports. Differences in microorganism carriage rates were also observed in relation to hygienic-epidemiological practices, seasons of the year, and the pre- or post-COVID-19 pandemic period. The hypothesis that colonization with S. aureus will be most frequently observed in the nose was confirmed

    Influence of mixed transition metal oxides on the polaronic conductivity of vanadate-phosphate glasses

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    U ovoj doktorskoj disertaciji istražena su strukturna i električna svojstva binarnih vanadatno-fosfatnih stakala, te ternarnih fosfatnih stakala u kojima je V2O5 zamijenjen s oksidima prijelaznih metala: WO3, MoO3 i Fe2O3. Struktura stakala istražena je Ramanovom spektroskopijom, a električna svojstva istražena su impedancijskom spektroskopijom. Istraživanje binarnog sustava pokazalo je da polaronska vodljivost u ovim staklima snažno ovisi o strukturi te je linearno povećanje vodljivosti s porastom udjela V2O5 posljedica ugradnje različitih vanadatnih poliedara koji se međusobno raznoliko povezuju u fosfatnoj mreži tvoreći višestruke pogodne puteve vodljivosti što povećava vjerojatnost polaronskih skokova. U ternarnim staklima zamjena V2O5 s WO3/MoO3 smanjuje polaronsku vodljivost, pri čemu se prijenos naboja odvija putem vanadatnih strukturnih jedinica. Kod stakala s Fe2O3, vodljivost pokazuje duboki minimum pri 27 % množinskog udjela Fe2O3 što se pripisuje prijelazu mehanizma iz transporta kroz dominantno vanadatnu strukturu u transport kroz strukturu s miješanim željeznim i vanadatnim jedinicama u kojoj ioni željeza doprinose polaronskom transportu.In this doctoral dissertation, the structural and electrical properties of binary vanadate-phosphate glasses, as well as ternary phosphate glasses where V2O5 is replaced with transition metal oxides, WO3, MoO3, and Fe2O3, were investigated. The glass structure was examined using Raman spectroscopy, while electrical properties were studied by impedance mspectroscopy. Research on the binary system revealed that polaronic conductivity in these glasses strongly depends on structure, with a linear increase in conductivity with increasing V2O5 content being a consequence of incorporating different vanadate polyhedra that are interconnected in the phosphate network, forming multiple favourable conductivity paths that increase the likelihood of polaronic jumps. In ternary glasses, replacing V2O5 with WO3/MoO3 reduces polaronic conductivity, with charge transfer occurring through vanadate structural units. In Fe2O3 glasses, conductivity exhibits a deep minimum at 27% Fe2O3 molar fraction, attributed to a transition from transport through a predominantly vanadate structure to transport through a mixed iron-vanadate structure where iron ions contribute to polaronic transport

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