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    Antibiotics consumption in contracted primary oral health practices in the Republic of Croatia during a five-year period

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    Cilj ovoga retrospektivnog istraživanja bio je prikazati potrošnju antibiotika propisanih u ugovornim ordinacijama dentalne medicine u Republici Hrvatskoj u petogodišnjem razdoblju. U razdoblju od početka 2015. godine do kraja 2019. godine prikupljeno je i obrađeno 1.535.139 podataka (e-Recepata) dobivenih s Centralnoga zdravstvenog informatičkog sustava Republike Hrvatske (CEZIH). Elektronički recepti sadržavali su podatke o propisanom antibiotiku, broju pakiranja te o poštanskom uredu ordinacija. Za prikaz potrošnje lijekova koristila se formula DDD/TSD (definirana dnevna doza/1000 stanovnika na dan), koja se izračunava: ukupna potrošnja mjerena u DDD-ima × 1000/365 × broj stanovnika. U toj se formuli kao broj stanovnika uzeo broj stanovnika dobiven od Državnog zvoda za statistiku, za godinu na koju se rezultati odnose. Potrošnja antibiotika porasla je od 1,98 DDD/TSD u 2015. godini na 2,10 DDD/TSD u 2019. godini. Zabilježeni su porast potrošnje amoksicilina s klavulanskom kiselinom (1,4 DDD/TSD u 2015. na 1,57 DDD/TSD u 2019.) i metronidazola (0,05 DDD/TSD u 2015. na 0,060 DDD/TSD u 2019., p < 0,05) te pad potrošnje klindamicina (0,11 DDD/TSD u 2015. na 0,10 DDD/TSD u 2019.) i cefaleksina (0,05 DDD/TSD u 2015. na 0,02 DDD/TSD u 2019., p < 0,05). U urbanoj sredini potrošnja je bila veća nego u ruralnoj (p < 0,05). Najčešća dijagnoza za koju se propisivao antiobiotik bila je periapikalni proces bez sinusa (20%). U gotovo 30% slučajeva antibiotici su propisivani za dijagnoze kod kojih nema indikacija, S obzirom na ukupnu potrošnju antibiotika u Republici Hrvatskoj u promatranom razdoblju, udjel potrošnje antibiotika propisanih u ugovornim ordinacijama dentalne medicine iznosio je oko 10% u petogodišnjem razdoblju.Aim: The aim of this research was to investigate antibiotics consumption issued in contracted dental offices in the Republic of Croatia in the period of five years. Materials and methods: This is a retrospective study. The data on the prescription of antibiotics in contracted dental practices were obtained from Croatian Health Insurance Fund (CHIF). Contracted dental practices are those with a legal agreement with the Croatian Health Insurance Fund. All prescription drugs by primary health care dental doctors, that have a contract with CHIF for the provision of health care, are recorded in the Central Health Information System of the Republic of Croatia (CEZIH). Each ePrescription contains a set of data about the prescribed drug (such as the drug name, active substance, dose, Anatomical Therapeutic Chemical Classification of the drug), the indication for the drug's use, patient identifier, date of prescription, the identifier of the doctor who prescribed the drug, and the identifier of the pharmacist's identifier who dispensed the drug. Accurate information on prescribed drugs was obtained from individual prescriptions, from which consumption was calculated using the number of defined daily doses per 1000 population per day (DID). Defined Daily Dose (DDD) is the average daily dose of a drug when used for its main indication in adults. DDD is assigned to drugs with an Anatomical Therapeutic Chemical (ATC) code and is determined based on the international use of the drug. Each ePrescription includes a diagnosis (indication) for the prescription of the drug. Diagnoses are encoded and classified according to the International Classification of Diseases and Related Health Problems (ICD codes). The classification of diseases can be defined as a system of categories assigned to specific diseases based on established criteria. ICD is a medical classification containing codes for diagnoses, signs, symptoms, and causes of injuries, published by the World Health Organization. The population estimate of the Republic of Croatia was obtained from the Croatian Bureau of Statistics. In Croatia, it is possible to obtain a private prescription (where the individual bears the cost) or a prescription a cost of which is covered by the Croatian Health Insurance Fund. Private prescriptions were not included in this study, and they accounted for 11% of the total drug consumption, unlike the total drug consumption covered by the CHIF, which was 89%. All trends were examined using linear regression and the Spearman correlation coefficient. A comparison of the number of issued drugs between rural and urban populations was made using the Chi-square test. Statistical testing was conducted at a significance level of 95% (p < 0.05). The results of statistical analysis are presented in tables and graphs. Results: The consumption of antibiotics during the observed period from 2015 to 2019 increased by 6%. Throughout this period, the most commonly prescribed antibiotic was amoxicillin with clavulanic acid, followed by amoxicillin, clindamycin, metronidazole and cephalexin and it accounted for a total of 80% of all prescribed antibiotics during that period. The highest consumption of antibiotics was for the combination of amoxicillin with clavulanic acid, followed by amoxicillin, clindamycin, metronidazole, and cephalexin. The consumption of amoxicillin with clavulanic acid in 2015 was 1.4 DID and has consistently increased each year. Over the observed period, consumption grew by 11.4%, reaching 1.57 DID in 2019 (p < 0.05). Concurrently, metronidazole consumption increased by 15.5% (p < 0.05), while amoxicillin consumption decreased by 6% from 0.31 DID to 0.29 DID (p < 0.05). The consumption of clindamycin decreased by 9.9%, amounting to 0.10 DID in 2019, and cephalexin consumption decreased by 42.7%, reaching 0.02 DID in 2019 (p < 0.05). Throughout the observed period, 877,673 prescriptions were issued to women and 705,415 to men. The data indicate that more antibiotics were prescribed to females (p < 0.05). The average age was 49.6 years, with a median of 51. The highest number of prescriptions, expressed in defined daily doses, was for the age group 18–65 years, with a 0.8% increase during the observed period. The number of prescriptions significantly increased by 23.9% in the age group 80+ (p < 0.05) and decreased by 16.2% for the age group 7–17 years (p < 0.05). In the age group 0–6, there was a 3.1% decrease, although it was not statistically significant. The most common diagnoses requiring antibiotic prescriptions in the conducted research were periapical abscess without sinus involvement, diseases of pulp and periapical tissues, chronic inflammation of the apical periodontium, pulp necrosis, acute inflammation of the apical periodontium of pulpal origin, pulpitis, acute periodontal inflammation, inflammatory conditions of the jaw, retained dental root, acute gingival inflammation, making up 80% of all diagnoses for which antibiotics were prescribed in the specified period. With regard to the total consumption of antibiotics in the Republic of Croatia in the observed period, the antibiotic consumption rate in contracted dental practices amounted to about 10% of national consumption in the five-year period. Conclusion: Based on the data from this study, from 2015–2020, regarding antibiotic consumption we can conclude that the consumption of antibiotics prescribed by public health general dentists has increased. The most prescribed antibiotics were amoxicillin with clavulanic acid, amoxicillin, clindamycin, metronidazole and cephalexin. Antibiotics were prescribed for clinical diagnoses for which antibiotics are not indicated or the indication was unclear. Additional education for dentists regarding antibiotics use is necessary as well as raising awareness among both dentists and patients on the growing global problem of antimicrobial resistance. Development of national guidelines for antibiotic use is essential

    Impact of previous chronic statin therapy on mortality in patients with acute myocardial infarction treated with primary percutaneous coronary intervention

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    Provedeno je prospektivno, kohortno istraživanje na seriji slučajeva koje je uključilo 2988 bolesnika (71.9% muškaraca), prosječne dobi 67 godina, koji su u razdoblju od 1. lipnja 2011. do 1. siječnja 2019. liječeni u Kliničkom bolničkom centru Sestre milosrdnice perkutanom koronarnom intervencijom zbog prvog infarkta miokarda. Kao primarni cilj istraživanja ispitivan je utjecaj ranije kronične terapije statinima na smrtnost bolesnika s infarktom miokarda. Medijan praćenja iznosio je 61 mjesec. Bolesnici su podijeljeni u dvije skupine, a ovisno o prethodnoj terapiji statinom. Analizirana je ukupna smrtnost (do kraja perioda praćenja) i kratkoročna smrtnost (unutar 30 dana od infarkta miokarda). Zasebno je analizirana opća i kardiovaskularna smrtnost. Od 2988 bolesnika, 420 (14.1%) je prethodno liječeno statinom, a u navedenoj je skupini zabilježena statistički značajnija opterećenost ranije utvrđenom aterosklerotskom bolesti i kardiovaskularnim komorbiditetima. Rezultati istraživanja nisu pokazali statistički značajnu razliku u smrtnosti među promatranim skupinama, kako kratkoročnoj tako dugoročnoj, čime je potvrđena nul-hipoteza. Promatrajući opću smrtnost, uočeno je da bolesnici prethodno liječeni statinima tijekom perioda praćenja umiru ranije od onih koji prethodno nisu liječeni statinima. Kao neovisni prediktori smrtnosti izdvojeni su: dob bolesnika, šećerna bolest, periferna arterijska bolest, ventrikulska tahikardija i visoki Killip stupanj u trenutku prijema. Kada se promatrao tip infarkta i angiografske karakteristike, uočeno je da su bolesnici liječeni statinima češće imali NSTEMI i angiografski neokluzivni tip infarkta, koji je ujedno bio i prediktor smrtnosti. Među laboratorijskim nalazima i rezultatima oslikavanja vrijednosti hemoglobina i ejekcijske frakcije lijevog ventrikula su se pokazale kao neovisni prediktori smrtnosti. Ovo istraživanje pokazalo je kako SCORE2 sustav dobro predviđa rizik smrti bilo kojeg uzroka bolesnika nakon infarkta miokarda, neovisno o prethodnom liječenju statinima. I visokorizični i nevisokorizični bolesnici imaju jednaku smrtnost tijekom perioda praćenja, neovisno o ranijem liječenju statinom.A prospective cohort study was conducted on a series of cases involving 2988 patients (71.9% male), with an average age of 67 years, who were treated at the Sestre milosrdnice University Hospital from June 1, 2011, to January 1, 2019, with percutaneous coronary intervention due to their first myocardial infarction. The primary aim of the study was to examine the impact of prior chronic statin therapy on mortality in patients with myocardial infarction. The median follow-up period was 61 months. Patients were divided into two groups based on previous statin therapy. Overall mortality (until the end of the follow-up period) and short-term mortality (within 30 days of myocardial infarction) were analyzed. All-cause and cardiovascular mortality were analyzed separately. Out of the 2988 patients studied, 420 (14.1%) had previously been treated with statins, and this group showed a statistically significant higher burden of previously diagnosed atherosclerotic disease and cardiovascular comorbidities. The results of the study did not show a statistically significant difference in mortality between the observed groups, both short-term and long-term, thus confirming the null hypothesis. Observing all-cause mortality, it was noted that patients previously treated with statins died earlier during the follow-up period than those who had not been previously treated with statins. Independent predictors of mortality included: patient age, diabetes mellitus, peripheral arterial disease, ventricular tachycardia, and high Killip class at admission. When considering the type of infarction and angiographic characteristics, it was noted that patients treated with statins more often had NSTEMI and angiographically non-occlusive type of infarction, which was also a predictor of mortality. Among the laboratory findings and imaging results, hemoglobin levels and ejection fraction were shown to be independent predictors of mortality. This study demonstrated that the SCORE2 system effectively predicts all-cause mortality, regardless of prior statin use. Both high-risk and non-high-risk patients did not show different mortality rates depending on prior statin therapy

    The effect of sound-vibration therapy on autonomic nervous system activity and on brain activity after intensive physical load

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    Introduction: All adaptive processes within and on the body triggered by training occur during recovery. The available literature and the number of studies on recovery following sports training significantly lag behind the knowledge concerning the active part of the training process. The central and autonomic nervous systems, under the influence of physical activity, are susceptible to fatigue, which significantly alters their functional characteristics. For this reason, it is necessary to study, develop, and apply recovery methods after physical activity to shorten the adaptation period, thereby making the training process more efficient and safer. The use of sound and sound vibrations for healing and achieving general well-being dates back to ancient times and is still intensively used in unchanged forms among some indigenous peoples today. Scientific research conducted, prompted by the effectiveness of this phenomenon, increasingly confirms its efficacy. Therefore, it is not only necessary but also imperative to explore the potential application of such practices in kinesiology. Research Objective and Hypotheses: The presented research aims to investigate the effects of sound-vibration therapy on the activity of the autonomic nervous system during recovery following a high-intensity physical activity protocol. From this aim, three hypotheses were derived: Hypothesis 1: Sound-vibration therapy significantly reduces sympathetic activity of the autonomic nervous system after a high-intensity physical activity protocol. Hypothesis 2: Sound-vibration therapy significantly increases parasympathetic activity of the autonomic nervous system after a high-intensity physical activity protocol. Hypothesis 3: Sound-vibration therapy significantly contributes to improving the speed and quality of recovery following intense sports training. In addition to the primary aim of determining the effects on the autonomic nervous system, this study investigates the effects of sound-vibration therapy on the activity of the central nervous system and subjective recovery impressions. Methodology: The methodology includes a qualitative-quantitative repeated measures experiment on the same group of trained amateur athletes subjected to intense sports training. Initial values of measured variables were recorded at the beginning of the protocol, followed by intense sports training. After completing the training, the subjects lay on a massage table for 45 minutes. In the control protocol, the subjects lay in silence during recovery, while the experimental protocol included an intervention with sound-vibration therapy under identical lying conditions. During recovery in both protocols, parameters of the central and autonomic nervous systems were measured. The subjective impression of the subjects was measured using the standardized Subjective Exercise Experiences Scale (SEES) and an additional subjective impression questionnaire, with personal descriptions evaluated descriptively and included as an appendix to the quantitative results. The Kolmogorov-Smirnov test was used to check the normality of the distribution of all variables. If a particular distribution was normal, data for that variable were presented as arithmetic means and standard deviations. If the data did not follow the normality of the Gaussian curve, data presentation was defined through medians and interquartile ranges (25th and 75th percentile). Data were analyzed using ANOVA for repeated measures to compare all points, and pairs of variables in case of confirmed significance. Also, pairs of variables before and after the intervention were tested using the Student's t-test for dependent samples or the Wilcoxon rank sum test for non-parametric statistics with a set significance level of p<0.05. The impact of the intervention was checked by calculating the effect size (Cohen's effect) and defined as small, moderate, or large. All analyses in this doctoral dissertation were conducted using SPSS version 23. Results: Although some trends were observed, the results did not show significant changes in the function of the central nervous system under the experimental protocol. On the other hand, the autonomic nervous system showed significant differences in the direction of increased parasympathetic activity, enhanced vagal tone, and reduced sympathetic influence during sound-vibration therapy compared to the protocol without its application. The assessment of subjective impressions using the SEES scale and the subjective impression questionnaire clearly indicated positive experiences towards recovery, qualitatively confirming the obtained quantitative findings. Conclusion: The analysis concluded that sound-vibration therapy with Tibetan singing bowls significantly contributes to a faster return of the autonomic nervous system to a stable state after intense physical activity by reducing sympathetic and increasing vagal influence, thus creating conditions for a higher quality and faster recovery of activated body systems. The impact of sound-vibration therapy (SVT) did not show a significant effect on the central nervous system. This is due to the rapid natural normalization of measured EEG activity, as it is not possible to conduct an intervention and measurements within the short period that offers stabilization of brain activity parameters (up to 6 minutes). Since central nervous system activity is not a relevant marker of recovery after intense sports activity, the lack of significant intervention impact did not affect the validation of the researched recovery using SVT. Furthermore, reviewing the results obtained from the SEES scale measurements and the descriptions of individual subjective experiences, the application of SVT significantly increased experience of personal well-being and reduced experience of fatigue and psychological distress after intense sports training. Theoretical and Practical Implications: This research is one of the first of its kind, making a step forward in exploring recovery techniques. Evidence of the effectiveness and practical applicability of this type of therapy suggests its use in practice for the purpose of better recovery, improved sports performance, injury prevention, and overall enhancement of athletes' quality of life.Uvod: Svi adaptacijski procesi u i na tijelu potaknuti treningom, događaju se tijekom oporavka. Dostupna literatura i broj istraživanja o oporavku nakon sportskog treninga značajno zaostaju za spoznajama o aktivnom dijelu trenažnog procesa. Središnji i autonomni živčani sustav, pod utjecajem fizičke aktivnosti, podložni su umoru koji značajno mijenja njihove funkcionalne karakteristike. Iz tog razloga potrebno je proučavati, razvijati i primjenjivati metode oporavka nakon fizičke aktivnosti, time skratiti vrijeme adaptacije te na taj način trenažni proces učiniti efikasnijim i sigurnijim. Korištenje zvuka i zvučnih vibracija u cilju iscjeljenja i postizanja opće dobrobiti seže daleko u prošlost, a kod nekih nativnih naroda u neizmijenjenom obliku intenzivno se koriste i danas. Provedena znanstvena istraživanja potaknuta učinkovitošću ovog fenomena sve ozbiljnije potvrđuju njegovu učinkovitost. Stoga ne samo potrebito nego je i nužno istražiti mogućnosti uporabe ovakve prakse u kineziologiji. Cilj i hipoteze istraživanja: Prezentirano istraživanje ima za cilj istražiti učinke zvučno-vibracijske terapije na aktivnost autonomnog živčanog sustava tijekom oporavka nakon protokola umaranja visoko intenzivnom tjelesnom aktivnosti. Iz postavljenog cilja proizašle su tri postavljene hipoteze: Hipoteza 1: Zvučno-vibracijska terapija značajno smanjuje simpatičku aktivnost autonomnog živčanog sustava nakon protokola umaranja visoko intenzivnom tjelesnom aktivnosti. Hipoteza 2: Zvučno-vibracijska terapija značajno povećava parasimpatičku aktivnost autonomnog živčanog sustava nakon protokola umaranja visoko intenzivnom tjelesnom aktivnosti. Hipoteza 3: Zvučno-vibracijska terapija značajno doprinosi poboljšanju brzine i kvalitete oporavka nakon intenzivnog sportskog treninga. Uz zadani cilj utvrđivanja učinaka na autonomni živčani sustav, prezentirani rad istražuje učinke zvučno-vibracijske terapije na aktivnost središnjeg živčanog sustava i subjektivne dojmove oporavka. Metodologija: Metodologija obuhvaća kvalitativno-kvantitativni eksperiment ponovljenih mjerenja na istoj skupini treniranih amaterskih sportaša podvrgnutih intenzivnom sportskom treningu. Mjerenje inicijalnih vrijednosti mjerenih varijabli obavljano je na početku protokola nakon čega je slijedio intenzivan sportski trening. Po obavljenom treningu ispitanici bi legli na stol za masažu gdje su ostali ležati 45 minuta. U kontrolnom protokolu ispitanici su za vrijeme oporavka samo ležali u tišini dok je eksperimentalni protokol, uz identične uvjete ležanja, uključivao i intervenciju zvučno-vibracijskom terapijom. Tijekom oporavka u oba protokola mjereni su parametri središnjeg i autonomnog živčanog sustava. Subjektivni dojam ispitanika mjeren je standardiziranom Skalom subjektivnog doživljaja vježbanja (Subjective Exercise Experiences Scale - SEES) uz koju je još dodatnim Upitnikom subjektivnog dojma i opisom vlastitim riječima procjenjivan njihov subjektivni doživljaj. Subjektivni opis vlastitog doživljaja kvalificiran je opisno i priložen kao dodatak kvantitativnim rezultatima. Kolmogorov-Smirnovljevim testom je testirana normalnost distribucije svih varijabli. Ukoliko se pojedina distribucija pokazala normalnom, podaci za tu varijablu prikazani su kao aritmetičke sredine i standardne devijacije, a ako podaci ne prate normalnost Gaussove krivulje, prikaz podataka je definiran kroz medijane i interkvartilne raspone (25.-ti i 75.-ti percentil). Podaci su obrađeni s pomoću ANOVE za ponavljajuća mjerenja radi usporedbe svih točaka, a parovi varijabli u slučaju potvrde značajnosti. Također parovi varijabli prije i poslije intervencije testirani su Studentovim t-testom za zavisne uzorke ili Wilcoxonovim testom parova u slučaju neparametrijske statistike uz postavljenu razinu značajnosti p<0,05. Utjecaj intervencije je provjeren izračunom čimbenika učinka (Cohenov učinak) i definiran je kao malen, umjeren ili veliki. Rezultati: Iako su vidljivi neki trendovi, rezultati nisu zabilježili značajne promjene na razini funkcije središnjeg živčanog sustavu pod utjecajem eksperimentalnog protokola. S druge strane, autonomni živčani sustav pokazao je značajne razlike u smjeru povećanja parasimpatičke aktivnosti, jačanju vagusnog tonusa i smanjenju simpatičkog utjecaja tijekom zvučno-vibracijske terapije u odnosu na protokol bez njene primjene. Procjena subjektivnog dojma SEES skalom i Upitnikom subjektivnog dojma vlastitim riječima nedvojbeno su pokazali pozitivna iskustva u smjeru oporavka i kvalitativno potvrdili dobivene kvantitativne nalaze. Zaključak: Analiza je zaključno pokazala kako zvučno-vibracijska terapija tibetanskim zvučnim zdjelama značajno doprinosi bržem povratku autonomnog živčanog sustava u stabilno stanje nakon intenzivne fizičke aktivnosti smanjenjem simpatičkog i povećanjem vagalnog utjecaja, stvarajući tako uvjete kvalitetnijeg i bržeg oporavka aktiviranih tjelesnih sustava. Utjecaj zvučno-vibracijske terapije (ZVT) nije pokazao značajan utjecaj na središnji živčani sustav. Razlog tome je prebrza prirodna normalizacija mjerene EEG aktivnosti. Naime, nije moguće napraviti intervenciju i mjerenja u tako kratkom periodu koji nudi vrijeme stabilizacije parametara moždane valne aktivnosti (do 6 min). Budući da EEG aktivnost središnjeg živčanog sustava nije relevantan marker oporavka nakon intenzivne sportske aktivnosti, iako nije zabilježen značajan utjecaj intervencije, to nije utjecalo na dokazivanje istraživanog oporavaka primjenom ZVT-a. Nadalje, uvidom u rezultate dobivene mjerenjem SEES skalom kao i u opise pojedinačnih subjektivnih iskustava ispitanika, uz primjenu ZVT-a utvrđeno je značajno povećanje osjećaja osobne dobrobiti kao i smanjenje osjećaja umora i psihološkog distresa nakon intenzivnog sportskog treninga

    Stocks and stock changes of carbon in dead organic matter and soil in Croatia's forests

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    Republika Hrvatska potpisnica je Okvirne konvencije Ujedinjenih naroda o promjeni klime, Kyotskog protokola i Pariškog sporazuma prema kojima se obvezala jednom godišnje izraditi i dostaviti Nacionalno izvješće o inventaru stakleničkih plinova (engl. National Greenhouse Gas Inventory Report, NIR). Promjene zaliha ugljika u šumskim ekosustavima obračunavaju se u sektoru „Korištenje zemljišta, prenamjena zemljišta i šumarstvo” (engl. Land Use, Land-Use Change and Forestry, LULUCF) za pet pohraništa ugljika: nadzemna i podzemna živa biomasa, mrtvo drvo, šumska prostirka i organska tvar tla. Procjena promjena zaliha ugljika u mrtvom drvu, šumskoj prostirci i tlu često je izostavljena zbog nedostatka dostupnih podataka i faktora promjene zaliha ugljika. Glavni cilj ovog istraživanja je omogućiti unaprjeđenje procjene zaliha u mrtvom drvu i šumskoj prostirci te procjene zaliha i promjena zaliha ugljika u mineralnom dijelu tla u šumama Republike Hrvatske. Ovo istraživanje uključuje postavljanje terenskog istraživanja za mrtvo drvo za deset vrsta drveća u tri biogeografske regije u Republici Hrvatskoj; sastavljanje nove nacionalne baze podataka o šumskoj prostirci; validaciju procesnog modela Biome-BGCMuSo (BBGCMuSo) verzija 4.0 za procjenu nacionalnih zaliha ugljika u mineralnom dijelu tla do dubine od 30 cm (SOC30), i treću izmjeru SOC30-a u pokusu kronosekvence hrasta lužnjaka, koja je zajedno sa dvije prethodne izmjere, poslužila za validaciju novije verzije modela BBGCMuSo v.6.2 za procjenu promjena zaliha SOC30-a. Zaliha ugljika u mrtvom drvu u Republici Hrvatskoj, procijenjena u ovom radu, manja je za 11–27 % u odnosu na vrijednost koja se trenutno koristi u NIR-u Republike Hrvatske. Korištenje nove nacionalne baza podataka o zalihama ugljika u šumskoj prostirci može povećati odlive CO2 iz ovog pohraništa ugljika za 5 % u odnosu na vrijednost koja se trenutno koristi u NIR-u Republike Hrvatske. Model BBGCMuSo može uspješno reproducirati prosječne zalihe SOC30-a za stratume šumskog zemljišta koji se koriste u NIR-u Republike Hrvatske, šume listača i šume četinjača, ali pri detaljnijoj stratifikaciji rezultata na razinu stratuma šumskog zemljišta × biogeografska regija smanjena je točnost modela. Kalibracija BBGCMuSo modela v.6.2 naglašava važnost korištenja skupova podataka različite vremenske rezolucije u kalibraciji procesnih modela. U šumi hrasta lužnjaka, predstavljenoj pokusom kronosekvence, trendovi izmjerenog i modeliranog SOC30-a, iako statistički neznačajni, suprotnog su smjera (negativan za izmjereni i pozitivan za modelirani SOC30). Dobiveni rezultati potencijalno mogu pridonijeti unaprjeđenju izračuna u NIR-u Republike Hrvatske.The Republic of Croatia, as a signatory country of the United Nations Framework Convention on Climate Change (UNFCCC), Kyoto Protocol and Paris Agreement, has committed to annually report on greenhouse gas (GHG) emissions and removals in its National GHG Inventory Report (NIR). In the forest ecosystems, carbon stock changes need to be accounted for under the Land Use, Land-Use Change and Forestry (LULUCF) sector for five ecosystem carbon pools: above- and below-ground live biomass, dead wood (DW), forest floor and soil organic matter (SOM). The estimation of carbon stock changes in DW, forest floor and SOM pools is often omitted due to a lack of available activity data and carbon stock change factors. The main aim of this research is to facilitate the improvement of estimates of carbon stocks in DW and forest floor, as well as carbon stocks and carbon stock changes in SOM in forest ecosystems in Croatia. This research includes the implementation of a field experiment on DW for ten forest tree species distributed across three biogeographical regions (BGR) in Croatia; a compilation of a new national dataset on forest floor; a validation of the process-based model Biome-BGCMuSo (BBGCMuSo) version 4.0 for estimating national soil organic carbon stocks down to 30 cm depth (SOC30), and a third measurement of SOC30 in pedunculate oak chronosequence that will be used, with previous two measurements, for validation of the newest model version BBGCMuSo v.6.2 for estimating SOC30 changes. The estimate of carbon stock in the DW pool from this study is lower by 11–27% compared to the value currently used in the Croatian NIR. A newly compiled national database on forest floor carbon stocks can facilitate the increase of net CO2 removals for 5% under this carbon pool in the Croatian NIR. BBGCMuSo v.4.0 model was shown to be suitable for the estimation of the overall mean of SOC30 for deciduous and coniferous Forest land strata reported in the Croatian NIR, but disaggregation of the results with respect to biogeographical region decreased model accuracy. Calibration of the BBGCMuSo model v.6.2 highlights the importance of using different temporal resolution datasets in calibration of process-based models. In the pedunculate oak forest, represented by the chronosequence experiment, although there is no disagreement in trends between the measured and modelled SOC30, the trends were divergent (negative for measured and positive for modelled SOC30). The obtained results have the potential to contribute to the improvement of calculations in Croatian NIR

    SETTING ASIDE THE ARBITRAL AWARD

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    Činjenica što Zakon o arbitraži od dana usvajanja u Saboru, odnosno već više od 20 godina, nije doživio niti jednu izmjenu ili dopunu, ukazivala bi prvo na zaključak da se radi o "idealnom" zakonu koji sadrži sve one elemente i načela arbitražnog postupka koja u potpunosti odgovaraju težnjama stranaka za efikasnim rješavanjem sporova i težnji zakonodavca da ga u potpunosti uskladi s modernim arbitražnim zakonodavstvima. S druge strane, njegova nepromijenjenost toliki niz godina može ukazati i na činjenicu da se mali broj pravnih znanstvenika i stručnjaka na području Republike Hrvatske uopće bavi arbitražnom "problematikom", pa stoga potreba za izmjenama ili dopunama Zakona o arbitraži nije u fokusu zakodavca. Oba zaključka su pred autora stavila zadatak da pokuša utvrditi jesu li zaista, nakon toliko godina od dana donošenja Zakona o arbitraži, potrebne njegove izmjene, odnosno može li hrvatski Zakon o arbitraži postati još efikasniji instrument zaštite prava i interesa stranaka, prvenstveno prava na pošteno suđenje i prava na djelotvorno pravno sredstvo. Zadatak je autora i utvrditi može li određenim izmjenama Zakona o arbitraži i drugih mjerodavnih zakona, arbitražni sud postati šire prihvaćen među strankama kao mjesto za rješavanje njihovih sporova, jer je činjenica da je arbitražno rješavanje sporova rijetkost u odnosu na rješavanje sporova pred državnim sudom. U tom cilju su analizirana komparativna arbitražna zakonodavstva Austrije, Švicarske i Engleske, analizirani su domaći i međunarodni pravni izvori kojima je uređena arbitraža, kao i brojne sudske odluke donesene u postupcima za pobijanje pravorijeka. Namjerno koristim riječ "pobijanje" pravorijeka, jer riječ "poništaj" nije zajednička arbitražnim zakonodavstvima koja su obrađena za potrebe ovog doktorskog rada. Prikazom i analizom rada sudova u postupcima povodom zahtjeva za pobijanje pravorijeka, zatim u postupcima povodom izjavljenih pravnih sredstava protiv odluka kojima je odlučeno o zahtjevima za pobijanje pravorijeka kao i analizom postupanja stranaka u tim postupcima, cilj je ovim radom prikazati i koliko je zaista efikasan učinak pravomoćnosti arbitražnog pravorijeka. Stoga su ovim doktorskim radom i predložene de lege ferenda određene izmjene Zakona o arbitraži. Cilj je ovog rada i ukazati strankama arbitražnog postupka na nužnost poduzimanja određenih radnji već u arbitražnom postupku jer kasnije isticanja prigovora na određene nepravilnosti nastale tijekom arbitražnog postupka više ne može utjecati na pravilnost donesenog pravorijeka. Ovim doktorskim radom pokušava se dati i odgovor koliko procesni zakoni mogu utjecati na efikasnost arbitražnog postupka i arbitražnog pravorijeka. Prije svega se misli na Zakon o parničnom postupku koji je petnaest puta izmijenjen i dopunjen od dana donošenja Zakona o arbitraži. Obzirom da se postupak za poništaj pravorijeka vodi prema pravilima redovne parnice, dakle u skladu s odredbama Zakona o parničnom postupku, analizira se i koliko učestale izmjene toga zakona utječu na efikasnost postupka za poništaj pravorijeka i na prava i obveze stranaka u tim postupcima. Analizira se i koliko je istražno načelo prisutno u postupcima za poništaj pravorijeka, način postupanja sudova te moguće odluke sudova u tim postupcima. Ovim će se doktorskim radom dati i odgovor na pitanje je li nužna još jedna izmjena procesnog zakonodavstva kako u postupcima za poništaj pravorijeka stranke ne bi zlouporabom svojih prava odgodile provedbu učinka pravomoćnosti pravorijeka. Analiza arbitražnih i parničnih procesnih odredbi bitnih za izradu teme ovog doktorskog rada, dovela je i do zaključka da ne postoje prepreke za osnivanjem novih arbitražnih ustanova koje nesmetano mogu organizirati provođenje arbitražnih postupaka. Koliko je opravdano to očekivati, ovisi i u znantoj mjeri o širenju arbitrabilnosti i na one sporove za koje je, za sada, sudska praksa ukazala da se mogu rješavati samo pred državnim sudovima. Širenje arbitrabilnosti na druge vrste sporova ovisi jedino i isključivo o volji zakonodavca, pa se već samo iz toga razloga, nadamo prvim izmjenama Zakona o arbitraži i novim izmjenama drugih zakona koje bi podržale i arbitražno rješavanje sporova proizlašlih iz odnosa koji su uređeni tim zakonima. Za ukazati je i na mišljenje da bi širenje "prisilnih arbitraža" znatno doprinjelo rasterećenju državnih sudova, ali za to je osim zakonodavnih izmjena, nužno prije svega i sudsko razumjevanje značenja toga pojma i njegove dozvoljenosti.The fact that the Arbitration Act, since its adoption in the Parliament more than 20 years ago, has not undergone a single change or amendment would firstly point to the conclusion that it is an "ideal" Act which contains all those elements and principles of the arbitration procedure which fully correspond to aspirations of the parties for efficient resolution of disputes and to the aspirations of the legislator to fully harmonize it with modern arbitration legislation. On the other hand, its unchanged nature for so many years may also indicate the fact that a small number of legal scholars and experts in the Republic of Croatia deals with arbitration "problems" at all, and therefore the need for changes or amendments to the Arbitration Act is not in the focus of the legislator. Both conclusions set the author with the task of trying to determine whether, after so many years since the adoption of the Arbitration Act, its changes are necessary, or whether the Croatian Arbitration Act can become an even more effective instrument for protecting the rights and interests of the parties, primarily the right to a fair trial and the right to an effective legal remedy. Task of the author is also to determine whether certain amendments to the Arbitration Act and other relevant laws can make the arbitration court more widely accepted among the parties as a place for resolving their disputes, since the fact is that arbitral dispute resolution is a rarity compared to the resolution of disputes before a regular court. To this end, the comparative arbitration legislation of Austria, Switzerland and England, the domestic and international legal sources regulating arbitration as well as numerous court decisions made in proceedings for the rebuttal of judgments were analysed. I intentionally use the word "contest" of the award since the word "setting aside" is not common to the arbitration legislature that have been dealt with for the purposes of this doctoral thesis. By presenting and analysing the work of the courts in proceedings following requests for contesting of awards, in proceedings regarding submitted legal remedies against decisions on requests for contesting of awards, as well as by analysing the actions of the parties in these proceedings, the aim of this doctoral thesis is to demonstrate how effective really is the valid arbitral award. Therefore, this doctoral thesis proposes de lege ferenda certain changes to the Arbitration Act. The aim of this doctoral is to point out to the parties to the arbitration procedure the necessity of undertaking certain actions already in the arbitration procedure, since later indication of objections to certain irregularities occurred during the arbitration procedure can no longer affect the regularity of the reached award. This doctoral thesis tries to provide a response to what extent procedural regulations can affect the efficiency of the arbitration procedure and the arbitration award. Firstly, reference is made to the Civil Procedure Act, which has been amended and supplemented fifteen times since the adoption of the Arbitration Act. Given that the procedure for the setting aside of an award is conducted according to the rules of court litigation, i.e. in accordance with the provisions of the Civil Procedure Act, it is analysed in what way often changes to Civil Procedure Act affect the efficiency of the procedure for setting aside of the award and the rights and obligations of the parties in those procedures. It is also analysed to what extent the investigative principle is present in the procedures for the setting aside of an award, the way the courts act and the possible decisions of the courts in these procedures. This doctoral thesis will also present an answer to the question of whether another amendment to the procedural legislation is necessary so that in procedures for the setting aside of awards, the parties would not, by abusing their rights, delay the execution of the final awards. The analysis of arbitration and litigation procedural provisions essential for the preparation of the theme of this doctoral thesis, led to the conclusion that there are no obstacles to the establishment of new arbitration institutions that can organize the conduct of arbitration proceedings without obstruction. How justified it is to expect the said, depends to a certain extent on the expansion of arbitrability and on those disputes for which, for the time being, judicial practice has indicated that can only be resolved before regular courts. The expansion of arbitrability to other types of disputes depends solely and exclusively on the will of the legislator, so for this reason alone, we hope for the first amendments to the Arbitration Act and for new amendments to other laws that would support the arbitration settlement of disputes arising from relationships regulated by those laws. It is also worth pointing out to the opinion that the expansion of "forced arbitrations" would significantly contribute to the relief of regular courts, but for this, in addition to legislative changes, it is necessary, first of all, a judicial understanding of the meaning of this term and its permissibility

    PREVENTION OF CELL DEATH DUE TO THERMAL OSTEONECROSIS BY USING NEWLY DESIGNED MEDICAL DRILLS

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    Termička osteonekroza je oštećenje kosti koje nastaje tijekom medicinskih intervencija u ortopediji i traumatologiji. Pri bušenju kosti dolazi do porasta temperature uz mjesto bušenja. Kad porast temperature i vrijeme izlaganja povišenoj temperaturi premašuju kritične razine, nastaju nepovratna oštećenja stanica. Da bi se termičko oštećenje kosti preveniralo, mjesto bušenja potrebno je hladiti ili rabiti drukčiji dizajn svrdala od dosadašnjih, koja manje zagrijavaju okolno tkivo. U tu svrhu dizajnirana su dvostupnjevana svrdla s više kombinacija užeg i šireg stupnja te je uspoređena razlika porasta temperature sa standardnim svrdlima bušenjem na umjetnom materijalu. Bušenje na kostima izvedeno je odabranim kombinacijama svrdala s najvećim potencijalom smanjenja porasta temperature, a uzorci koštanog tkiva s ruba provrta kvantitativno su histološki analizirani. Ovo istraživanje pokazalo je da se kod dvostupnjevanih svrdala razvijaju manje temperaturu okolne kosti od standardnih svrdala te da je oštećenje stanica proporcionalno porastu temperature. Dvostupnjevana svrdla primjenjiva su u ortopediji i traumatologijiThermal osteonecrosis is bone damage that occurs during medical interventions in orthopaedics and traumatology. The temperature in the procedures of drilling bones rises near the drilling site. When the temperature rises and the time of exposure to elevated temperature exceeds critical levels, irreversible cell damage occurs. In order to prevent thermal damage to the bone, it is necessary to cool the drilling site or use a different design of drills, which causes less temperatures and less damage to the surrounding tissue. For this purpose, two-stage drills with several combinations of narrower and wider stages were designed, and the difference in temperature rise was compared with standard drill bits, by drilling on artificial material. Drilling on bone tissue samples was performed with selected drill combinations which proved to have the greatest potential to reduce the temperature rise. These samples were quantitatively histologically analyzed. This study showed that two-stage drills develop a lower bone temperature than standard drills and that cell damage is proportional to temperature rise. Twostage drills are applicable in orthopaedic surgery

    Synthesis and properties of novel diamondoid ethers

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    U okviru ove doktorske disertacije provedena je sinteza novih tercijarnih diamantoidnih etera koji se sastoje od adamantanske i diamantanske podjedinice direktno povezane kisikovim atomom. Uz klasičnu sintezu u otopini/talini, provedena je i mehanokemijska sinteza koja je pokazala brojne prednosti u usporedbi s klasičnom sintezom. Novopripravljenim spojevima ispitana je mogućnost samoorganizacije u 2D i 3D prostoru pri čemu su korištene tehnika pretražne tunelirajuće mikroskopije, tehnika helijevih nanokapljica te tehnika difrakcije rendgenskog zračenja na jediničnom kristalu. Uočeno je uređeno samoudruživanje diamantoidnih etera pri čemu način samoorganizacije proizlazi iz početnih geometrijskih struktura ispitivanih molekula te je proces uzrokovan prostornim međumolekulskim interakcijama. Za dodatnu karakterizaciju nastalih površinskih slojeva korištena je računalna analiza kojom je razjašnjen utjecaj kisikovog atoma na usmjeravanje molekula prema površini, te je potvrđen presudan utjecaj Londonovih disperzijskih interakcija između diamantoidnih kaveza na samoorganizaciju adsorbiranih molekula. Analiza difrakcijom rendgenskog zračenja i diferencijalnom pretražnom kalorimetrijom potvrdila je postojanje faznih transformacija diamantoidnih etera u čvrstom stanju.In the scope of this thesis, new tertiary diamondoid ethers consisting of adamantane and diamantane subunits directly connected by an oxygen atom were prepared. In addition to classical synthesis in solution/melt, mechanochemical synthesis was also carried out, which showed numerous advantages compared to classical synthesis. The self-organization of the newly prepared compounds in 2D and 3D space was investigated using the technique of scanning tunneling microscopy, the technique of helium nanodroplets and the technique of single crystal X-ray diffraction. Ordered self-assembly of diamondoid ethers was observed, whereby the manner of self-organization was a consequence of the initial geometrical structures of the investigated molecules and the process was governed by spatial intermolecular interactions. For additional characterization of the formed surface layers, computational analysis was used in order to clarify the influence of oxygen atoms on the orientation of molecules with respect to the surface, while London dispersion interactions between diamondoid cages were confirmed as a driving force for the self-organization of the adsorbed molecules. X-ray diffraction and differential scanning calorimetry analyses confirmed the existence of phase transformations of diamondoid ethers in the solid state

    The relationship of tertiary education and productivity in the labor market

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    Istraživanje razmatra utjecaj obrazovanih ishoda na tržište rada u posttranzicijskim zemljama EU, s fokusom na Hrvatsku i utjecaj masovnizacije visokog obrazovanja na produktivnost.The study explores the impact of educational outcomes on labor markets in EU post-transition countries, focusing on Croatia and the effect of higher education massification on productivity

    Klasifikacija digitalnih signala korištenjem adaptivnih informacijskih entropijskih mjera i strojnoga učenja : doktorski rad

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    This thesis proposes a new approach for preprocessing method for signal classification based on blind source separation of signal components from noisy data in the timefrequency domain. The method is based on the local entropy, which is calculated within adaptive, data-driven 2D regions. One of the advantages of the proposed technique is that it requires no prior knowledge of the signal, its components or the noise, but the processing is performed on the noisy signal mixtures. Furthermore, the method is robust to the selection of time-frequency distributions and entropy measures. The proposed approach is demonstrated using several examples. The first example is synthetic signals with different signal-to-noise ratios. This example is selected to demonstrate the usage of the proposed method and the analysis of the results. The second example is a real example of speech signals. This example was selected to demonstrate the ability to use the proposed method on real-life signals. In addition, a novel entropy measure was introduced and adapted to improve the detection within the method. Finally, the method was presented as a preprocessing tool for signal detection of seismology signals, and the results of time-frequency representations and entropy maps were compared. The results obtained by evaluating different machine learning models for classification show excellent classification performance of the proposed approach, with classification accuracy, area under the receiver operating characteristic curve, F1-score and Matthews correlation coefficient up to 97.55%, 97.72%, 98.07% and 94.88%, respectively. Moreover, the proposed approach significantly outperforms the model trained on the time-frequency distributions in terms of all considered metrics, with statistical significance confirmed by Cohran’s Q and McNemar tests. The obtained results indicate that the proposed technique improves the classification of seismological signals and has the potential to be extended to other practical applications of signal classification in other areas of research.Analiziranje nestacionarnih signala predstavlja kompleksan zadatak u različitim istraživačkim područjima zbog njihovog promjenjivog frekvencijskog spektra kroz vrijeme. Takva analiza zahtijeva korištenje naprednih alata kako bi se istovremeno prikazali u vremenskoj i frekvencijskoj domeni, što nadilazi standardne tehnike analize signala u tim pojedinačnim domenima. Osim toga, nestacionarni signali u stvarnim situacijama često su višekomponentni i dodatno su izloženi šumovima iz vanjske okoline. U ovom radu razvijena je i testirana metoda za odvajanje komponenti signala od okolnog šuma bez da su potrebne dodatne informacije o prirodi signala i šuma. Metoda je bazirana na adaptivnim izračunima lokalnih entropija unutar vremensko-frekvencijske distribucije signala. Metoda je testirana na tri različita sintetička signala. Svakom signalu dodane su tri različite razine šuma čime se dobilo devet slučajeva. Za svaki od njih dobiveno je pet vremensko-frekvencijskih distribucija što je razultiralo s 45 slučajeva. Za svaki slučaj metoda je provedena koristeći tri klasične entropijske mjere i mjeru neizravne entropije koja je bila adaptirana upravo za rad s predloženom metodom. Konačno, test je imao 180 slučajeva. Rezultati su pokazali kako predložena metoda može razdvojiti signal i šum s točnošću od 89.8% do 99.5% za slučajeve kada je u signalu prisutno više šuma, odnosno u odnosu signal-šum šum prevladava, te od 89.7% do 99.9% kada je šum slabiji, odnosno signal nadjačava šum. F1 mjera se kreće izmedu 61.2% i 90.8% za slučajeve s jačim šumom te između 64.8% i 97.3% kod slučajeva s više šuma. Ukupno gledano najbolje rezultate ostvaruje predložena adaptacija entropijske mjere s najvišom točnošću između različitih vremensko-frekvencijskih distribucija izmedu 94.5% i 99.9% te F1 mjerom između 78.2% i 97.3%. Nakon toga, metoda je testirana na primjeru audio signala iz javno dostupne baze s različitim izvorima šuma i različitim odnosima signala i šuma. Dobiveni rezultati imaju točnost između 97.78% i 99.03%, preciznost između 98.94% i 99.65% te odziv između 98.96% i 99.65%. Završni cilj je bio pokazati kako se predložena metoda može koristiti kao metoda za predobradu signala sa svrhom klasifikacije signala. Testni slučaj je bila klasifikacija potresa i šuma kod seizmografskih signala . Rezultati su pokazali kako korištenje entropijske mape dobivene iz predložene metode mogu poboljšati rezultate klasifikacije u odnosu na dosad korišteni vremensko-frekvencijski prikaz signala. Postignuta su poboljšanja do 2.64% za točnost, do 2.34% poboljšanje kod površine ispod krivulje odnosa specifičnosti i osjetljivosti, F1 mjera je poboljšana do 2.16% i Matthew-ov koeficijent korelacije je imao povećanje do 5.38%. Analiza dobivenih rezultata pokazuje da je predloženi pristup primjene adaptivnog prozora za izračun lokalne entropije uspješan u odvajanju signala od šuma. Također ukazuju i na to da je entropijska mapa dobivena predloženom metodom korisna kao korak predobrade signala za unaprijeđenje kvalitete klasifikacije seizmoloških signala. Predložena metoda za predobradu signala može se proširiti i za korištenje na drugim područjima znanstvenog istraživanja različitih vrsta signala

    Morfološka i elektrofiziološka karakterizacija stanica spiralnog ganglija in vitro uzgojenih na komplementarnom poluvodiču sa elektrodnim sustavima visoke gustoće

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    Objectives: This study investigated a micro-patterned, high-density complementary metal–oxide semiconductor (CMOS) electrode array to be used as a biologically permissive environment for organization, guidance, and simultaneous electrical stimulation and recording of spiral ganglion neurons (SGN). Methods: SGNs extracted and isolated from cochleae of P5-P7 rat pups and adult guinea pigs were cultured for 1, 4, and 7 days in vitro on glass coverslips (control) and CMOS electrode array. The cultures were analyzed visually and immunohistochemically for SGN presence, outgrowth, neurite alignment, neurite length, neurite asymmetry, and the contact of neuronal soma and neurites with the microelectrodes. Electrophysiological experiments were performed at 37° using a CMOS-like electrode array in two modes. The first, spontaneous, mode focuses on recording intrinsic spontaneous electrophysiological activity without external stimulation to determine whether cells can fire action potentials in the absence of a standard neurotransmitting mechanism via hair cells, while the second, stimulation mode recorded potential cell responses to an electrical biphasic stimulus (positive phase first) with a total duration of 60 µs and an amplitude of 500 nA or 800 nA. Results: Our findings indicate that the topographical environment of the CMOS chip with micro-patterned pillars enhanced growth, survival, morphology, neural orientation, and alignment of SGNs in vitro compared to control. Smaller spacing (0.8-1.6 µm) between protruding pillars on CMOS led SGNs to develop structured and guided neurites oriented along three topographical axes separated by 60°. These results constitute a morphological basis for positioning the microelectrodes on the chip appropriate for direct contact with SGNs. This configuration allowed the CMOS electrode array to electrically stimulate the SGN, whose responses were observed with live Fluo 4 calcium imaging and, at the same time, recorded electrophysiologically using the same CMOS electrode array. The average maximum spike amplitude was 135.4 ± 15.2 µV for recorded spontaneous activity and 130 ± 10 µV for recorded neural activity after stimulation. Conclusion: To the best of our knowledge, this study demonstrates for the first time that simultaneous stimulation and recording with the same electrode array is feasible for measuring auditory neuronal activity from dissociated SGNs. Immunostaining of SGNs cultures grown on a CMOS electrode array for the neuronal marker Tuj revealed both somata and processes of neurons on the electrode surface, in accordance with results that the position of neuronal soma and neurites affects recordings of electrical activity on the CMOS electrode array. The model presented in this study represents a novel in vitro tool to investigate strategies for simultaneous electrical stimulation and recording of auditory neurons to optimize CI technology.Cilj: Ova studija istraživala je mogućnost korištenja elektrodnog sustava visoke gustoće temeljenog na CMOS tehnologiji, kao biološki prihvatljivog okruženja za organizaciju, navođenje te električnu stimulaciju živčanih stanica spiralnog ganlija (engl. SGNs). Metode: Stanice spiralnog ganglija, ekstrahirane i izolirane iz pužnica 5-7 dana starih (P5-P7) štakorskih mladunaca i odraslih zamoraca, uzgajane su 1, 4 i 7 dana in vitro na stakalcima (kontrola) te CMOS čipovima. Kulture su analizirane vizualno i imunohistokemijski na prisutnost živčanih stanica spiralnog ganglija, na rast, poravnanje neurita, duljinu neurita, asimetriju neurita te kontakt neuronske some i neurita sa elektrodama. Elektrofiziološki pokusi izvedeni su na 37°C u dva eksperimentalna modusa sa svrhom detekcije živčane aktivnosti koristeći elektrodni sustav koji se temelji na CMOSu. Prvi modus je usredotočen na snimanje intrizične, spontane elektrofiziološke aktivnosti bez vanjske stimulacije kako bi se utvrdilo mogu li neuroni generirati akcijske potencijale u odsutnosti standardnog mehanizma neurotransmisije putem osjetilnih slušnih stanica. Drugi modus je uključivao stimulaciju pomoću koje su bili zabilježeni potencijalni stanični odgovori na električni bifazični podražaj (s prvom pozitivnom fazom) s ukupnim trajanjem od 60 µs i amplitudom od 500 nA ili 800 nA. Rezultati: Rezultati pokazuju, da je topografsko okruženje CMOS čipa sa mikroiglicama poboljšalo rast, preživljavanje, morfologiju te neuralnu orientaciju in vitro uzgojenih živčanih stanica spiralnog ganglija u usporedbi sa kontrolom. Manji razmak (0.8-1.6 µm) između mikroiglica na CMOS čipu doveo je stanice spiralnog ganglija do razvoja strukturiranih i vođenih neurita usmjerenih duž tri topografske osi pomaknutih za 60°. Ti rezultati čine morfološku osnovu za pozicioniranje mikroelektroda na čipu prikladnih za izravan kontakt sa stanicama spiralnog ganglija. Ova konfiguracija je omogućila uspješnu električnu stimulaciju stanica spiralnog ganglija čiji su odgovori promatrani uživo pomoću Fluo 4 oslikavanja kalcija na CMOS čipu. Prosječna maksimalna vršna amplituda je bila 135.4 ± 15.2 µV za zabilježenu spontanu aktivnost te 130 ± 10 µV za zabilježenu živčanu aktivnost nastalu kao odgovor na stimulaciju. Ova studija pokazuje da je istovremena stimulacija te snimanje s istim elektrodnim sustavom elektroda visoke gustoće izvedivo za mjerenje elektrofiziološke aktivnosti živčanih stanica dobivenih iz in vitro kultura stanica spiralnog ganglija. Imunohistokemijsko bojanje kultura uzgojenih na CMOS čipu za neuronski marker Tuj otkrilo je tijela stanica (some) i procese (neurite) neurona na površini elektroda, te u skladu s rezultatima, pokazuje, da položaj neurona i neurita utječe na snimanje električne aktivnosti na CMOS čipu. Model predstavljen u ovoj studiji predstavlja pogodan in vitro alat za istraživanje stimulacijskih protokola za istovremenu električnu stimulaciju i snimanje živčanih stanica spiralnog ganglija u svrhu optimizacije tehnologije kohlearnih implantata (engl. CI)

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