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Drug-induced kidney injury frequently leads to aborted clinical trials and drug withdrawals. Sufficiently sensitive sensors capable of detecting mild signs of chemical insult in cell-based screening assays are critical to identifying and eliminating potential toxins in the preclinical stage. Oxidative stress is a common early manifestation of chemical toxicity, and biomolecule carbonylation is an irreversible repercussion of oxidative stress. Here, we present a novel fluorogenic assay using a sensor, TFCH, that responds to biomolecule carbonylation and efficiently detects modest forms of renal injury with much greater sensitivity than standard assays for nephrotoxins. We demonstrate that this sensor can be deployed in live kidney cells and in renal tissue. Our robust assay may help inform preclinical decisions to recall unsafe drug candidates. The application of this sensor in identifying and analyzing diverse pathologies is envisioned.

Soluble urokinase-type plasminogen activator receptor (suPAR) is a risk factor for kidney diseases. Here we report the presence of C-terminal suPAR fragment, D2D3, in patients with diabetic nephropathy. D2D3-positive human sera inhibited glucose-stimulated insulin release in human islets and were associated with patients requiring insulin therapy. D2D3 transgenic mice presented kidney disease and diabetes marked by decreased levels of insulin and C-peptide, impaired glucose-stimulated insulin secretion, decreased pancreatic β-cell mass, and high fasting glucose. D2D3 fragment dysregulated glucose-induced cytoskeletal dynamics, impaired maturation and trafficking of insulin granules, and inhibited bioenergetics of β-cells in culture. An anti-uPAR antibody restored β-cell function in D2D3 transgenic mice. We show that the D2D3 fragment injures the kidney and pancreas, offering a unique dual therapeutic approach for kidney diseases and insulin-dependent diabetes.SummaryProteolytic suPAR fragment, D2D3, simultaneously injures two organs, the kidney and pancreas, thus causing a dual organ disease.

Background: The Covid-19 pandemic has changed the digitalisation level of education. Many institutions had some knowledge and practical background in delivering lectures online. Some countries apply a top-down digitalisation approach driven by policy or strategy and externally impacted by the government. Some other countries rather initiate digitalisation internally by teachers and universities. Objectives: The main goal is to investigate the digitalisation level of the higher education system in Croatia, exploring the digitalisation of economic disciplines compared to other scientific fields. Methods/Approach: We assess the digitalisation level of higher education based on the regulatory framework, applied approach of digitalisation, the agility of transition to online teaching and the existing number of courses and online study programs. Education digitalisation in different countries is compared with the Croatian experience. Results: Although the satisfactory level of higher education institutions’ agility to switch online exist, there hasn’t been a centralised project led by the government and supported by proper funds to increase digitalisation in Croatia. Even before the pandemic, many e-courses from economics and business had been offered to students, but online study programs were exceptions, covering mainly the economics and business field. Conclusions: The Covid-19 pandemic has improved the digitalisation process in the Croatian education system. A general framework for the digitalisation of education should be developed containing the detailed administrative processes and appropriate funds to be implemented.

BACKGROUND: Acute kidney injury is common, with a major effect on morbidity and health care utilization. Soluble urokinase plasminogen activator receptor (suPAR) is a signaling glycoprotein thought to be involved in the pathogenesis of kidney disease. We investigated whether a high level of suPAR predisposed patients to acute kidney injury in multiple clinical contexts, and we used experimental models to identify mechanisms by which suPAR acts and to assess it as a therapeutic target. METHODS: We measured plasma levels of suPAR preprocedurally in patients who underwent coronary angiography and patients who underwent cardiac surgery and at the time of admission to the intensive care unit in critically ill patients. We assessed the risk of acute kidney injury at 7 days as the primary outcome and acute kidney injury or death at 90 days as a secondary outcome, according to quartile of suPAR level. In experimental studies, we used a monoclonal antibody to urokinase plasminogen activator receptor (uPAR) as a therapeutic strategy to attenuate acute kidney injury in transgenic mice receiving contrast material. We also assessed cellular bioenergetics and generation of reactive oxygen species in human kidney proximal tubular (HK-2) cells that were exposed to recombinant suPAR. RESULTS: The suPAR level was assessed in 3827 patients who were undergoing coronary angiography, 250 who were undergoing cardiac surgery, and 692 who were critically ill. Acute kidney injury developed in 318 patients (8%) who had undergone coronary angiography. The highest suPAR quartile (vs. the lowest) had an adjusted odds ratio of 2.66 (95% confidence interval [CI], 1.77 to 3.99) for acute kidney injury and 2.29 (95% CI, 1.71 to 3.06) for acute kidney injury or death at 90 days. Findings were similar in the surgical and critically ill cohorts. The suPAR-overexpressing mice that were given contrast material had greater functional and histologic evidence of acute kidney injury than wild-type mice. The suPAR-treated HK-2 cells showed heightened energetic demand and mitochondrial superoxide generation. Pretreatment with a uPAR monoclonal antibody attenuated kidney injury in suPAR-overexpressing mice and normalized bioenergetic changes in HK-2 cells. CONCLUSIONS: High suPAR levels were associated with acute kidney injury in various clinical and experimental contexts. (Funded by the National Institutes of Health and others.)

U kontekstu razmatranja uspješnosti poslovanja poduzeća, obično se razmatra visina dobiti poduzeća u relativnom smislu, odnosno kao povrat u odnosu na određenu bazu, što ukazuje na profitabilnost poduzeća. Budući da, ovisno o konkretnoj situaciji i potrebi, ima smisla promatrati različite odnose u financijskim izvještajima, tako je razvijen relativno veliki broj različitih pokazatelja profitabilnosti. Pokazatelji koji su u praksi vrlo česti su EBIT i EBITDA marža. Pitanje koje se pritom postavlja je jesu li te mjere same za sebe dobri i dovoljni pokazatelji profitabilnosti poslovanja poduzeća te postoje li situacije gdje mogu navoditi na krivi zaključak. U teorijskom dijelu rada sistematizirani su različiti načini na koje se može mjeriti profitabilnost poslovanja poduzeća, s posebnim naglaskom na razmatranje potencijalnih nedostataka prezentiranih mjera, što je potkrijepljeno prijašnjim istraživanjima u tom području. Za potrebe istraživačkog dijela rada oblikovan je uzorak poduzeća koja posluju u Republici Hrvatskoj. Na temelju njihovih financijskih izvještaja za 2017. godinu izračunati su odabrani pokazatelji profitabilnosti s ciljem ispitivanja jačine povezanosti između pojedinih pokazatelja. Za potrebe izračuna koeficijenata korelacije prvo su promatrane originalne vrijednosti pokazatelja, a zatim je isti postupak ponovljen s rangovima poduzeća po pojedinom pokazatelju. Istraživanje je pokazalo da postoji pozitivna, ali izrazito slaba korelacija između EBIT i EBITDA marže (kao pokazatelja koji se računaju samo na temelju računa dobiti i gubitka) te rentabilnosti vlastitog kapitala i rentabilnosti imovine (kao pokazatelja koji uzimaju u obzir i informacije iz bilance). Razlike su najizraženije u slučaju poduzeća koja su više opterećena dugovima te imaju veći udio dugotrajne imovine koja se amortizira. To znači da korisnici financijskih izvještaja mogu doći do vrlo različitih zaključaka o profitabilnosti poslovanja poduzeća, ovisno o tome koji financijski pokazatelj razmatraju. EBIT i EBITDA marža su u tom kontekstu samo parcijalni pokazatelji uspješnosti, budući da potencijalno isključuju značajan dio rashoda poduzeća, a također ne uzimaju u obzir ulogu brzine obrtaja imovine u povećanju profitabilnosti. Njihova upotreba je stoga ograničena te ih je preporučljivo kombinirati sa sveobuhvatnijim pokazateljima profitabilnosti.

Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived circulating signaling molecule that has been implicated in chronic kidney disease, such as focal segmental glomerulosclerosis (FSGS). Typically, native uPAR (isoform 1) translates to a 3-domain protein capable of binding and activating integrins, yet the function of additional isoforms generated by alternative splicing is unknown. Here, we characterized mouse uPAR isoform 2 (msuPAR2), encoding domain I and nearly one-half of domain II, as a dimer in solution, as revealed by 3D electron microscopy structural analysis. In vivo, msuPAR2 transgenic mice exhibited signs of severe renal disease characteristic of FSGS with proteinuria, loss of kidney function, and glomerulosclerosis. Sequencing of the glomerular RNAs from msuPAR2-Tg mice revealed a differentially expressed gene signature that includes upregulation of the suPAR receptor Itgb3, encoding β3 integrin. Crossing msuPAR2-transgenic mice with 3 different integrin β3 deficiency models rescued msuPAR2-mediated kidney function. Further analyses indicated a central role for β3 integrin and c-Src in msuPAR2 signaling and in human FSGS kidney biopsies. Administration of Src inhibitors reduced proteinuria in msuPAR2-transgenic mice. In conclusion, msuPAR2 may play an important role in certain forms of scarring kidney disease.

BackgroundTransient receptor potential channel 5 (TRPC5) is a non-selective cationic ion channel expressed in brain, kidney and other organs where its activation underlies podocyte injury in chronic kidney diseases. Specifically, it has been suggested that a podocyte TRPC5 plasma membrane relocation and channel activation following injury results from activation of Rac-1, propagating podocyte dysfunction and proteinuria. However, previous TRPC5 transgenic mouse studies had questioned a pathogenic role for TRPC5 in podocytes. This investigation was designed to specifically evaluate podocyte Rac-1 activation in the context of functional TRPC5 or a TRPC5 pore mutant to assess effects on proteinuria.Materials and MethodsWe employed single cell patch-clamp studies of cultured podocytes and studied proteinuria in transgenic mouse models to characterize the effects of TRPC5 following podocyte Rac-1 activation.ResultsInhibition of TRPC5 by small molecules reportedly ameliorated proteinuria in murine models of proteinuric kidney diseases. In order to directly examine TRPC5 function following Rac-1-induced podocyte injury, we analyzed TRPC5 inhibition in podocyte specific Rac-1 (active) transgenic mice. In addition, we generated a double-transgenic mouse constitutively overexpressing either TRPC5 (TRPC5WT) or a TRPC5 dominant-negative pore mutant (TRPC5DN) in concert with podocyte specific and inducible activation of active Rac-1 (Rac-1Dtg). In electrophysiological experiments, active TRPC5 was detected in primary podocytes overexpressing TRPC5 but not in podocytes with endogenous TRPC5 expression, nor with Rac-1 overexpressing podocytes. TRPC5 inhibition did not change proteinuria in mice with active podocyte Rac-1, nor did an increase or loss of TRPC5 activity affected podocyte injury in Rac-1Dtg animals. Administration of TRPC5 inhibitors, ML204 and AC1903, did not alleviate podocyte Rac-1 induced proteinuria.ConclusionTRPC5 inhibition did not modify podocyte Rac-1 induced proteinuria in mice.Significance StatementTRPC5 is a calcium conducting ion channel involved in a plethora of biological functions in the brain, kidney and other organs. In proteinuric kidney diseases, others proposed a model that links activation of small GTPase Rac-1 in podocytes to activation of TRPC5 channels propagating cellular injury and eventually leading to progressive kidney disease. To test this hypothesis, we have developed a novel transgenic mouse model that employs podocyte Rac-1 activation in the presence or absence of a functional TRPC5 channel. Our data shows that transgenic mice with activated Rac-1 in podocytes did not enhance endogenous TRPC5 expression or its activity. Furthermore, TRPC5 blockade or activation did not modify Rac-1 induced proteinuria in mice.

Accounting treatment of research and development (R&D) costs has been the subject of debate and disagreement for decades, with no solution or regulatory harmonization in sight. The reasons do not lie in the treatment of research costs, because everyone agrees that the future economic benefits behind these costs are too uncertain and that they should be treated as an expense. However, costs of development create quarrels. Standard setters cannot agree on whether they should be capitalized or presented as an expense. It is interesting that, regardless of the prescribed accounting treatment, there is criticism for the existing approach and advocacy for the opposite approach. This is because both approaches have their drawbacks. In addition to exploring how R&D expenditures are defined and measured, we focus on investigating accounting treatment of R&D in different sets of standards. Since treatment of R&D costs is subject to criticism, we further investigate the issues and misuses of this type of costs, primarily related to earnings management. In the end, we illustrate how different accounting treatment affects company’s financial stability and performance.

The hotel industry, among others, has been affected by the COVID-19 pandemic. The effect of the pandemic can be noticed through financial statements. The aim of the chapter is to analyse how the COVID-19 pandemic has affected the financial position and business performance of the hotels in a tourism-oriented country such is Croatia. The chapter covers the basic information of tourism and the features of the hotel industry in Croatia. The authors represent the sets of national recommendations for dealing with the pandemic in the tourism sector that are enriched with available macroeconomic statistical data. Further, the analysis of financial statements of the five selected hotels is presented. The analysis was done in order to provide comparative analysis of financial results in the pandemic environment (2020) and the previous year (2019). Based on the calculated liquidity, solvency, activity, economy, and profitability ratios, the authors conclude that all the mentioned ratios worsened in 2020 for all the observed hotels.

External audit of financial statements plays a key role in achieving transparent financial reporting, since its purpose is to provide reasonable assurance that the presented financial statements are free of material misstatements due to fraud or error. In the process of fulfilling this role, auditors must be adaptable, especially when it comes to technological advancements. This chapter explains the effect that new technologies have on audit of financial statements. In addition to summarizing the technological changes that impacted the audit profession in the past and therefore introduced new generations of audit, the authors have identified issues and challenges in the way the audit is currently performed. Some of the new technologies that are discussed in this chapter have the potential to mitigate these issues. However, new challenges and risks may be introduced with accepting these technologies in the process of financial reporting and auditing.

The selectivity of the glomerular filter is established by physical, chemical, and signaling interplay among its three core constituents: glomerular endothelial cells, the glomerular basement membrane, and podocytes. Functional impairment or injury of any of these three components can lead to proteinuria. Podocytes are injured in many forms of human and experimental glomerular disease, including minimal change disease, focal segmental glomerulosclerosis, and diabetes mellitus. One of the earliest signs of podocyte injury is loss of their distinct structure, which is driven by dysregulated dynamics of the actin cytoskeleton. The status of the actin cytoskeleton in podocytes depends on a set of actin binding proteins, nucleators and inhibitors of actin polymerization, and regulatory GTPases. Mutations that alter protein function in each category have been implicated in glomerular diseases in humans and animal models. In addition, a growing body of studies suggest that pharmacological modifications of the actin cytoskeleton have the potential to become novel therapeutics for podocyte-dependent chronic kidney diseases. This review presents an overview of the essential proteins that establish actin cytoskeleton in podocytes and studies demonstrating the feasibility of drugging actin cytoskeleton in kidney diseases.

A common manifestation of drug toxicity is kidney injury or nephrotoxicity. Nephrotoxicity frequently leads to termination of clinical trials and drug withdrawals, which jeopardize biomedical progress. Efficient preclinical screening platforms capable of detecting mild signs of kidney damage, which may elicit considerable toxic response in vivo, are essential. A common manifestation of chemical toxicity is oxidative modification of cellular biomolecules. Therefore, we have developed a facile biomolecule carbonyl detection assay that well surpasses the sensitivity of the standard assays in identifying modest forms of renal injury. Using a novel fluorogenic sensor, TFCH, we have demonstrated the applicability of the assay in live kidney cells and in renal tissue. This robust assay can help inform preclinical decisions to recall unsafe drug candidates. Application of this assay in identifying and analyzing diverse pathologies is envisioned.

Proteinuria encompasses diverse causes including both genetic diseases and acquired forms such as diabetic and hypertensive nephropathy. The basis of proteinuria is a disturbance in size selectivity of the glomerular filtration barrier, which largely depends on the podocyte: a terminally differentiated epithelial cell type covering the outer surface of the glomerulus. Compromised podocyte structure is one of the earliest signs of glomerular injury. The phenotype of diverse animal models and podocyte cell culture firmly established the essential role of the actin cytoskeleton in maintaining functional podocyte structure. Podocyte foot processes, actin-based membrane extensions, contain 2 molecularly distinct "hubs" that control actin dynamics: a slit diaphragm and focal adhesions. Although loss of foot processes encompasses disassembly of slit diaphragm multiprotein complexes, as long as cells are attached to the glomerular basement membrane, focal adhesions will be the sites in which stress due to filtration flow is counteracted by forces generated by the actin network in foot processes. Numerous studies within last 20 years have identified actin binding and regulatory proteins as well as integrins as essential components of signaling and actin dynamics at focal adhesions in podocytes, suggesting that some of them may become novel, druggable targets for proteinuric kidney diseases. Here we review evidence supporting the idea that current treatments for chronic kidney diseases beneficially and directly target the podocyte actin cytoskeleton associated with focal adhesions and suggest that therapeutic reagents that target the focal adhesion-regulated actin cytoskeleton in foot processes have potential to modernize treatments for chronic kidney diseases.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a common cause of end stage renal disease (ESRD) with a high rate of recurrence after kidney transplantation. Several factors such as white race, rapid progression, and previous allograft failure due to recurrence were found to be risks of recurrence. Data are limited on the benefits of rituximab and/or therapeutic plasma exchange (TPE) in preventing recurrence. In this study, we sought to assess the efficacy of rituximab and TPE for the prevention and treatment of recurrent FSGS post kidney transplantation. METHODS: We enrolled 66 patients with FSGS in this prospective observational study and followed their outcomes. Patients with high risk for recurrence received preventative therapy with TPE and/or rituximab. RESULTS: Twenty three of the thirty seven (62%) who received preventative therapy developed recurrence compared to fourteen recurrences out of the twenty seven (51%) who did not receive any therapy (p=0.21). There was a trend for less relapse when rituximab was used as a therapy for recurrent FSGS, (6/22 versus 9/18, p=0.066). We utilized a clinical score of 5 values to assess the prediction of FSGS recurrence. A score of 3 or more had a predictive Receiver Operating Characteristic (ROC) curve of 0.72. Treatment with TPE and/or rituximab resulted in better allograft survival than historical studies. Allograft failure due to recurrent FSGS occurred in only 6 patients (9%). CONCLUSION: Preventative therapies do not decrease the recurrence rate of recurrent FSGS. However, prompt treatment of recurrence with these therapies may result in improved outcomes.

Soluble urokinase plasminogen activator receptor is a novel biomarker strongly predictive of cardiovascular outcomes implicated in the pathogenesis of kidney disease. Soluble urokinase plasminogen activator receptor levels, however, correlate with declining kidney function. It is unclear whether soluble urokinase plasminogen activator receptor levels remain associated with outcomes in patients with ESRD.We measured plasma soluble urokinase plasminogen activator receptor levels in 1175 patients (mean age =66±8 years old, 54% men) with type 2 diabetes mellitus on hemodialysis participating in the German Diabetes and Dialysis Study followed for a median of 4 years for outcomes including all-cause death, cardiovascular events, and infection-related mortality. Survival analysis was performed using stepwise Cox proportional hazards models adjusted for potential confounders. Also, adjustments were made for inflammatory markers (C-reactive protein and leukocyte count) and the oxidative stress marker asymmetric dimethyl arginine to investigate potential mediators of the relationship between soluble urokinase plasminogen activator receptor and outcomes.Median soluble urokinase plasminogen activator receptor levels were 10,521 pg/ml (interquartile range, 9105-12,543 pg/ml). When stratified by tertiles, patients with soluble urokinase plasminogen activator receptor11,633 pg/ml (third tertile) had adjusted 1.6-fold higher mortality (hazard ratio, 1.60; 95% confidence interval, 1.27 to 2.03) compared with those with low soluble urokinase plasminogen activator receptor9599 pg/ml (first tertile). Risks of sudden death and stroke were higher (adjusted hazard ratio, 1.98; 95% confidence interval, 1.27 to 3.09 and adjusted hazard ratio, 1.74; 95% confidence interval, 1.05 to 2.90, respectively), together accounting for higher incidence of cardiovascular events (adjusted hazard ratio, 1.48; 95% confidence interval, 1.15 to 1.89). Associations with outcomes persisted after adjusting for C-reactive protein, leukocyte count, and asymmetric dimethyl arginine. Addition of soluble urokinase plasminogen activator receptor to a risk factor model modestly improved risk discrimination for all-cause death (The association of soluble urokinase plasminogen activator receptor levels with outcomes persists in patients on hemodialysis. Additional study is warranted to characterize the underlying pathways of that association, which may yield opportunities to develop new therapeutic strategies.

The paper subscribes to a current concern related to audit profession and auditing practices during pandemic times and has a two- fold objective. The first one gravitates around performing a review of the recent official opinions in the field of audit and corporate governance and its contribution to the overall economic indicators. The second objective aims at identifying the institutional, regulatory, economic and financial environment indicators that may exert an impact on the strength of auditing and reporting standards, to uncover whether country-specific environments contribute to strengthening the quality of audits. The empirical analysis comprises 28 European countries, covering a timeframe from 2000 to 2019 and relies on a panel regression framework. The set of explanatory variables considered comprises: i) a financial environment proxy, represented by the Index of Financial Stress ; ii) an economic development variable, represented by GDP per capita growth rate ; iii) country governance indicators, such as the political stability, the regulatory quality, the control of corruption and the economic policy uncertainty. A dummy variable related to the status of a country’s membership to the Eurozone will be also tested, to reveal whether the strength of auditing and reporting standards is determined by the country’s membership to this group. Another dummy variable included in the analysis is related to the occurrence of the 2008 global financial crisis and is meant to serve as a proxy for another global turmoil time, similar to the one witnessed at present. The conclusions will allow us to formulate some remarks and expectations regarding the potential impact of the pandemic on the strength of audit standards and the potential challenges that may arise in the future for this profession.

Usually the most important role of language is to facilitate communication, which often proves challenging if the used terminology is inconsistent, complex or not understandable. These issues may especially affect specific language that is characteristic for a certain profession, particularly when the members of the profession communicate the message to the outsiders. Literature review suggests that the accounting terminology may sometimes be perceived as complex or incomprehensible, due to multiple changes and variations of accounting terms. Since there is a lack of research in the field of higher education, a research was conducted with the aim of analyzing accounting terminology used in the higher education institutions in Croatia. Both secondary and primary data were used in the analysis. The secondary data included accounting courses curricula of a sample of higher education institutions in Croatia, which were analyzed in order to explore the consistency of accounting terminology. In addition, the research was supplemented by collecting primary data using questionnaire on the attitudes of students about the complexity of accounting terminology. The analysis of accounting terms used in accounting courses curricula led to a conclusion that the analyzed courses, in most cases, are not harmonized regarding the terminology used. However, these results were expected from the previous research, that showed that the same applies for the Croatian regulatory accounting framework, which is why it was concluded that using different synonyms for the same accounting concepts may be beneficial for students. As for the students’ attitudes towards accounting terminology, the students who participated in the research mostly agree that the accounting courses often use different synonyms for the same concept. Although they perceive this as confusing, they are also aware that using multiple synonyms during courses for the same accounting concepts is useful because it serves as a preparation for practice. On the other hand, they mostly disagree with the statement that the accounting terminology is too complex and incomprehensible, which has proved to be influenced by the students’ characteristics, such as the type of study program enrolled, year of study, number of accounting courses attended, secondary school type and working experience. This research complements previous research conducted in Croatia in other areas where the accounting terminology is present, such as the legislation or in practice among business professionals, which is its main scientific contribution As for the practical implications, results of the research may serve as an indicator to educators and legislators in their future actions, since the potential problem of inconsistency and complexity of accounting terminology in courses’ curricula are a direct consequence of inconsistency and complexity of terminology in accounting legislative., Najvažnija uloga jezika je obično olakšati komunikaciju, što često predstavlja izazov ako je upotrijebljena terminologija nedosljedna, složena ili nerazumljiva. Takvi problemi mogu posebno biti izraženi u slučaju specifičnog jezika koji je karakterističan za određenu profesiju, pogotovo u slučaju kad se zahtijeva komunikacija s osobama koje ne pripadaju toj profesiji. Sukladno pregledu literature, može se doći do zaključka da se računovodstvena terminologija ponekad smatra složenom ili neshvatljivom, primarno zbog čestih promjena ili varijacija korištenih računovodstvenih termina. Budući da je uočen nedostatak sličnih istraživanja u području visokog obrazovanja, provedeno je istraživanje s ciljem analize računovodstvene terminologije koja se koristi u institucijama višeg i visokog obrazovanja u Hrvatskoj. U analizi su korišteni sekundarni i primarni podaci. Sekundarni podaci obuhvaćali su nastavne planove i programe računovodstvenih kolegija institucija višeg i visokog obrazovanja iz uzorka, koji su analizirni kako bi se istražila ujednačenost korištene računovodstvene terminologije. Osim toga, istraživanje je dopunjeno prikupljanjem primarnih podataka pomoću upitnika o stavovima studenata vezano uz složenost računovodstvene terminologije. Analiza termina korištenih u nastavnim planovima i programima dovela je do zaključka da obuhvaćeni računovodstveni kolegiji u većini slučajeva nisu usklađeni po pitanju računovodstvene terminologije. Međutim, takvi rezultati su očekivani zahvaljujući rezultatima prijašnjih istraživanja, koja su pokazala da isto vrijedi i za regulatorni računovodstveni okvir u Hrvatskoj, zbog čega se može zaključiti da korištenje različitih računovodstvenih sinonima tijekom obrazovanja zapravo može biti korisno za studente. Što se tiče stavova studenata o računovodstvenoj terminologiji, pokazalo se da se studenti koji su sudjelovali u istraživanju uglavnom slažu da računovodstveni kolegiji često koriste različite sinonime za isti pojam. Iako im to djeluje zbunjujuće, svjesni su i da je upotreba višestrukih sinonima tijekom nastave korisna jer služi kao priprema za praksu. S druge strane, uglavnom se ne slažu s tvrdnjom da je računovodstvena terminologija presložena ili nerazumljiva, za što se pokazalo da u određenoj mjeri ovisi o njihovim pojedinačnim obilježjima, kao što su vrsta upisanog studija, godina studija, broj odslušanih računovodstvenih kolegija, vrsta pohađane srednje škole te radno iskustvo. Ovo istraživanje nadopunjuje prethodna istraživanja provedena u Hrvatskoj u drugim područjima gdje je prisutna računovodstvena terminologija, kao što su zakonodavstvo ili poslovna praksa, što je glavni znanstveni doprinos rada. Što se tiče praktičnih implikacija, rezultati istraživanja mogu poslužiti kao indikator osobama u obrazovnom sustavu i regulatorima, budući da je potencijalni problem nedosljednosti i složenosti računovodstvene terminologije u nastavnim planovima i programima direktna posljedica nedosljednosti i složenosti računovodstvene terminologije u računovodstvenoj regulativi.

Information technology has a particularly significant role in securing and distributing high quality information on business and financial performance, and the development of information technology causes great challenges for accounting profession. The application of information technology in accounting causes a “transformation of accounting practice” that requires from accountants’ development of new skills.Therefore, the main objective of this paper is to analyse the possibilities of applying new information technology in accounting practice through systematic analysis of recent studies and to investigate how the application of information technology affects the performance of accounting operations.In this context, there is a particularly significant impact of XBRL – the language of financial reporting, Cloud computing, Big Data, Data Analytics but also other emerging technologies like Artificial Intelligence.This paper also investigates future trends also most significant risks due to the use of information technology in accounting. Given their recent nature, the benefits of applying new information technologies in accounting have not yet been fully explored and their systematic analysis will serve as a basis for identifying directions of future development.

BackgroundRelatively high plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) have been associated with focal segmental glomerulosclerosis and poor clinical outcomes in patients with various conditions. It is unknown whether elevated suPAR levels in patients with normal kidney function are associated with future decline in the estimated glomerular filtration rate (eGFR) and with incident chronic kidney disease. MethodsWe measured plasma suPAR levels in 3683 persons enrolled in the Emory Cardiovascular Biobank (mean age, 63 years; 65% men; median suPAR level, 3040 pg per milliliter) and determined renal function at enrollment and at subsequent visits in 2292 persons. The relationship between suPAR levels and the eGFR at baseline, the change in the eGFR over time, and the development of chronic kidney disease (eGFR

Podocyte injury and loss mark an early step in the pathogenesis of various glomerular diseases, making these cells excellent targets for therapeutics. However, cell–based high–throughput screening assays for the rational development of podocyte-directed therapeutics are currently lacking. Here, we describe a novel high–content screening–based phenotypic assay that analyzes thousands of podocytes per assay condition in 96-well plates to quantitatively measure dose-dependent changes in multiple cellular features. Our assay consistently produced a Z′ value >0.44, making it suitable for compound screening. On screening with >2100 pharmacologically active agents, we identified 24 small molecules that protected podocytes against injury in vitro (1% hit rate). Among the identified hits, we confirmed an β1-integrin agonist, pyrintegrin, as a podocyte-protective agent. Treatment with pyrintegrin prevented damage-induced decreases in F-actin stress fibers, focal adhesions, and active β1-integrin levels in cultured cells. In vivo, administration of pyrintegrin protected mice from LPS–induced podocyte foot process effacement and proteinuria. Analysis of the murine glomeruli showed that LPS administration reduced the levels of active β1 integrin in the podocytes, which was prevented by cotreatment with pyrintegrin. In rats, pyrintegrin reduced peak proteinuria caused by puromycin aminonucleoside–induced nephropathy. Our findings identify pyrintegrin as a potential therapeutic candidate and show the use of podocyte–based screening assays for identifying novel therapeutics for proteinuric kidney diseases.

Dysregulation of the actin cytoskeleton in podocytes represents a common pathway in the pathogenesis of proteinuria across a spectrum of chronic kidney diseases (CKD). The GTPase dynamin has been implicated in the maintenance of cellular architecture in podocytes through its direct interaction with actin. Furthermore, the propensity of dynamin to oligomerize into higher-order structures in an actin-dependent manner and to cross-link actin microfilaments into higher-order structures has been correlated with increased actin polymerization and global organization of the actin cytoskeleton in the cell. We found that use of the small molecule Bis-T-23, which promotes actin-dependent dynamin oligomerization and thus increased actin polymerization in injured podocytes, was sufficient to improve renal health in diverse models of both transient kidney disease and CKD. In particular, administration of Bis-T-23 in these renal disease models restored the normal ultrastructure of podocyte foot processes, lowered proteinuria, lowered collagen IV deposits in the mesangial matrix, diminished mesangial matrix expansion and extended lifespan. These results further establish that alterations in the actin cytoskeleton of kidney podocytes is a common hallmark of CKD, while also underscoring the substantial regenerative potential of injured glomeruli and identifying the oligomerization cycle of dynamin as an attractive potential therapeutic target to treat CKD.

Direktiva i Uredba Europske unije o zakonskoj reviziji nalažu da društva od javnog interesa moraju imati organiziran revizijski odbor. Revizijska reforma, inicirana novim regulatornim okvirom na razini Europske unije, unijela je nova pravila koja, između ostalog, ojačavaju ulogu revizijskog odbora po pitanju njegovog sastava i kompetencija njegovih članova. Prema tome, većina članova revizijskog odbora treba biti neovisna, a članovi odbora kao cjelina moraju posjedovati znanje o sektoru u kojem posluje subjekt koji je predmet revizije. Uz zadaću nadziranja procesa obavljanja zakonske revizije financijskih izvještaja, njezinih nalaza i zaključaka, revizijski odbor odgovoran je za proceduru izbora ovlaštenog revizora ili revizorskog društva te prijedloga za njihovo imenovanje. Osim toga, revizijski odbor obavještava upravni odnosno nadzorni odbor o ishodu zakonske revizije, te ispituje i prati neovisnost revizora. Prema tome, vidljivo je da revizijska Direktiva daje značajnu odgovornost revizijskim odborima u nadzoru neovisnosti revizora. Glavni ciljevi rada su: 1) prikazati i sažeti ključne odgovornosti revizijskog odbora u kontekstu ostvarivanja ciljeva korporativnog upravljanja, 2) istražiti rezultate dosadašnjih istraživanja o doprinosu djelovanja revizijskih odbora kvaliteti eksterne revizije, 3) ispitati smatraju li revizori i korisnici revizije u Hrvatskoj revizijski odbor važnim čimbenikom kvalitete eksterne revizije. Izloženi nalazi primarnog istraživanja provedenog na uzorku ispitanika u Hrvatskoj pokazuju da svi ispitanici u prosjeku vrednuju utjecaj postojanja aktivnog i stručnog revizijskog odbora, kao i pravovremene komunikacije s revizorom, pozitivnima s aspekta utjecaja na kvalitetu revizije. To je posebno naglašeno na razini unutarnjih korisnika revizije kao zaposlenika revidiranih subjekata. Prema tome, revizijski odbor se može smatrati važnim čimbenikom kvalitete eksterne revizije.

Dynamin is a 96 kDa protein that has multiple oligomerization states that influence its GTPase activity. A number of different dynamin effectors, including lipids, actin filaments, and SH3-domain containing proteins, have been implicated in the regulation of dynamin oligomerization, though their roles in influencing dynamin oligomerization have been studied predominantly in vitro using recombinant proteins. Here, we identify higher order dynamin oligomers such as rings and helices in vitro and in live cells using fluorescence lifetime imaging microscopy (FLIM). FLIM detected GTP- and actin-dependent dynamin oligomerization at distinct cellular sites, including the cell membrane and transition zones where cortical actin transitions into stress fibers. Our study identifies a major role for direct dynamin-actin interactions and dynamin’s GTPase activity in the regulation of dynamin oligomerization in cells.

Podocytes are highly differentiated cells and critical elements for the filtration barrier of the kidney. Loss of their foot process (FP) architecture (FP effacement) results in urinary protein loss. Here we show a novel role for the neutral amino acid glutamine in structural and functional regulation of the kidney filtration barrier. Metabolic flux analysis of cultured podocytes using genetic, toxic, and immunologic injury models identified increased glutamine utilization pathways. We show that glutamine uptake is increased in diseased podocytes to couple nutrient support to increased demand during the disease state of FP effacement. This feature can be utilized to transport increased amounts of glutamine into damaged podocytes. The availability of glutamine determines the regulation of podocyte intracellular pH (pHi). Podocyte alkalinization reduces cytosolic cathepsin L protease activity and protects the podocyte cytoskeleton. Podocyte glutamine supplementation reduces proteinuria in LPS-treated mice, whereas acidification increases glomerular injury. In summary, our data provide a metabolic opportunity to combat urinary protein loss through modulation of podocyte amino acid utilization and pHi.

Gain-of-function mutations in the calcium channel TRPC6 lead to autosomal dominant focal segmental glomerulosclerosis and podocyte expression of TRPC6 is increased in some acquired human glomerular diseases, particularly in membranous nephropathy. These observations led to the hypothesis that TRPC6 overactivation is deleterious to podocytes through pathological calcium signaling, both in genetic and acquired diseases. Here, we show that the effects of TRPC6 on podocyte function are context-dependent. Overexpression of TRPC6 alone did not directly affect podocyte morphology and cytoskeletal structure. Unexpectedly, however, overexpression of TRPC6 protected podocytes from complement-mediated injury, whereas genetic or pharmacological TRPC6 inactivation increased podocyte susceptibility to complement. Mechanistically, this effect was mediated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activation. Podocyte-specific TRPC6 transgenic mice showed stronger CaMKII activation, reduced podocyte foot process effacement and reduced levels of proteinuria during nephrotoxic serum nephritis, whereas TRPC6 null mice exhibited reduced CaMKII activation and higher levels of proteinuria compared with wild type littermates. Human membranous nephropathy biopsy samples showed podocyte staining for active CaMKII, which correlated with the degree of TRPC6 expression. Together, these data suggest a dual and context dependent role of TRPC6 in podocytes where acute activation protects from complement-mediated damage, but chronic overactivation leads to focal segmental glomerulosclerosis.

The GTPase dynamin has captivated researchers for over two decades, even managing to establish its own research field. Dynamin's allure is partly due to its unusual biochemical properties as well as its essential role in multiple cellular processes, which include the regulation of clathrin-mediated endocytosis and of actin cytoskeleton. On the basis of the classic model, dynamin oligomerization into higher order oligomers such as rings and helices directly executes the final fission reaction in endocytosis, which results in the generation of clathrin-coated vesicles. Dynamin's role in the regulation of actin cytoskeleton is mostly explained by its interactions with a number of actin-binding and -regulating proteins; however, the molecular mechanism of dynamin's action continues to elude us. Recent insights into the mechanism and role of dynamin oligomerization in the regulation of actin polymerization point to a novel role for dynamin oligomerization in the cell.

Podocyte injury is a hallmark of the glomerular disease, which is a direct cause of chronic kidney diseases. Importantly, podocyte injury is a consequence of the dysregulation of the actin cytoskeleton. In diverse animal models of proteinuric glomerular disease, recovering the integrity of the actin structure in podocytes resulted in beneficial effects. In this review, we focus on the premise of targeting the actin cytoskeleton as a feasible therapeutics for treating chronic kidney diseases