The Methodology of Marking a Cyclotourist Route in the Corridor of an Abandoned Railway Track

Biciklizam u novije vrijeme postaje sve popularniji kao aktivnost u kojoj se biciklom služimo kao prijevoznim sredstvom, ali i kao turistička aktivnost i oblik rekreacije koji je istodobno koristan za ljudsko zdravlje te znatno povoljnije djeluje na okoliš od korištenja motornih vozila. To je utjecalo na proces stvaranja sve većeg broja obilježenih i neobilježenih cikloturističkih ruta po postojećim cestama koje su manje opterećene motornim prometom te na izgradnju posebnih biciklističkih traka uz postojeće ceste i posebnih biciklističkih staza i cesta namijenjenih isključivo biciklistima. Među njima su osobito popularne trase napuštenih željezničkih pruga koje se prenamjenjuju u biciklističke ceste, jer se radi o rutama koje zbog razmjerno malih nagiba trase, uvjetovanih potrebama željezničkog prijevoza, nisu zahtjevne za većinu cikloturista, a prolaze atraktivnim krajolicima. U ovom je radu prikazana metodologija planiranja revitalizacije napuštene pruge Bjelovar – Garešnica s odvojkom za Grubišno Polje za potrebe razvoja cikloturizma u Bjelovarsko-bilogorskoj županiji.Bicyclism has lately become increasingly popular as an activity in which bicycle is used not only as a means of transport, but also as a tourist activity, and a type of recreation useful for human health and considerably environment-friendlier than the use of motor vehicles. This has influenced the process of arranging an ever increasing number of marked and unmarked cyclotourist routes on the existing roads with less traffic in motor vehicles, as well as establishing special bicyclist tracks along the existing roads, and separate bicyclist paths and roads intended for bicyclists only. Particularly popular among them are abandoned railway tracks, which are converted into bicyclist roads, since due to the needs of railway transport, they have relatively gentle slopes. Thus, they are not too demanding for the majority of cyclotourists, whilst their attractiveness lies in the fact that they pass through beautiful landscape. The paper presents the methodology of planning the revitalisation of the abandoned railway track between Bjelovar and Garešnica with a branch line for Grubišno Polje for the needs of developing cyclotourism in the Bjelovar-Bilogora County

Development and potentials of sports-recreational aviation and avio tourism in Croatia

The development of aviation in Croatia began more than a century ago with the development of the adequate infrastructure, mostly hangars for building of aircraft and their servicing. In that long-lasting development of the Croatian aviation, the focus has been on the military and especially civil aviation already by the beginning of World War I, in Austrian - Hungarian Monarchy. This paper will describe the development of civil aviation but not the commercial public traffic than the sports-recreational aviation. Special care is dedicated to avio tourism, i.e. tourism that appears due to the activities connected with ultralight flying and air sports. Avio tourism and its development contribute to the total number of visits and the tourist\u27s consumption at tourist destinations which develop that kind of tourism. The paper concludes with some proposals for the development of the overall sports and recreational aviation and avio tourism

Case report: State-of-the-art risk-modifying treatment of sudden cardiac death in an asymptomatic patient with a mutation in the SCN5A gene and a review of the literature

Brugada syndrome is a rare hereditary disorder characterized by distinct ECG findings, complex genetics, and a high risk of sudden cardiac death. Recognition of the syndrome is crucial as it represents a paradigm of sudden death tragedy in individuals at the peak of their lives. Notably, Brugada syndrome accounts for more than 20% of sudden cardiac deaths in individuals with structurally normal hearts. Although this syndrome follows an autosomal dominant inheritance pattern, it is more prevalent and severe in males. Diagnosis is primarily based on the characteristic ECG pattern observed in the right precordial leads. Mutations in the SCN5A gene, resulting in loss of function, are the most common genetic cause. We presented a 36-year-old proband with a family history of sudden cardiac death. Although the patient was asymptomatic for Brugada syndrome, his father had experienced sudden death at the age of 36. The proband was admitted to St. Catherine's Specialty Hospital where blood was taken and subjected to next-generation sequencing (NGS) using a “Sudden cardiac death” panel. The analysis identified a pathogenic variant in the SCN5A gene [c.4222G > A(p.Gly1408Arg)], which is associated with autosomal dominant Brugada syndrome. Based on the positive genetic test result, the patient was referred for further examination. ECG with modified precordial lead positioning confirmed the presence of the Brugada phenotype, displaying the type-2 and type-1 ECG patterns. Therefore, we made the diagnosis and decided to implant an implantable cardioverter-defibrillator (ICD) based on the results of broad genetic NGS testing, diagnostic criteria (ECG), and considering the high burden of sudden cardiac death in the patient's family, as well as his concerns that limited his everyday activities. This case shows that genetics and personalized medicine hold immense potential in the primary prevention, diagnosis, and treatment of Brugada syndrome and sudden cardiac death

In silico analysis of genetic, transcription, epigenetic and protein changes of EGFR-PI3K-AKT-mTOR signaling pathway participants in diffuse gliomas of the brain

Difuzni gliomi heterogena su skupina tumora s agresivnim biološkim ponašanjem. Unatoč novim molekularnim saznanjima razlike između patohistoloških tipova su nedovoljno istražene. U ovoj in silico analizi istraživali smo uloge 8 gena, sudionika signalizacije EGFR-PI3K-AKT-mTOR, u gliomima mozga. Analiza AKT1, AKT2, AKT3, CHUK, GSK3β, EGFR, PTEN i PIK3AP1 napravljena je korištenjem podataka javno dostupne baze cBioPortal za tumorsku genomiku i transkriptomiku. Genske, transkripcijske, epigenetičke te proteinske promjene obrađene su na 751 uzorku (62 difuzna astrocitoma, 129 anaplastičnih astrocitoma te 560 glioblastoma). Rezultati su pokazali promjene u broju kopija (CNA od engl. copy number alteration) gena PTEN (76%), PIK3AP1 i CHUK (75% svaki), EGFR (74%), AKT2 (39%), AKT1 (32%), AKT3 (19%) te GSK3β (18%). Učestalost promjena razlikovala se između gradusa. Najveći broj CNA imali su glioblastomi u kojima su EGFR, PIK3AP1 i PTEN bili promijenjeni u 89%, CHUK u 88%, a AKT2 u 43% analiziranih uzoraka. Kruskal-Wallis test pokazao je značajnu razliku u metilaciji i ekspresiji mRNA ispitivanih gena između pojedinih gradusa. Korelacija rezultata sugerira da se geni AKT1, AKT2, EGFR i PIK3AP1 ponašaju kao onkogeni, a geni AKT3, CHUK, GSK3β i PTEN poput tumor supresora. Rezultati doprinose saznanjima o molekularnim razlikama između patohistoloških tipova glioma te mogu poslužiti za bolju klasifikaciju i poboljšanje metoda liječenja.Diffuse gliomas are a heterogeneous group of tumors with aggressive biological behavior. Despite new molecular findings, the differences between pathohistological types need to be explained better. In this in silico analysis, we investigated participants of EGFR-PI3K-AKT-mTOR signaling in brain gliomas. The analysis of AKT1, AKT2, AKT3, CHUK, GSK3β, EGFR, PTEN, and PIK3AP1 was performed using data from the publicly available cbBioPortal database. 751 samples (62 diffuse astrocytoma, 129 anaplastic astrocytoma and 560 glioblastomas) revealed changes at genetic, transcriptome, epigenome, and protein levels. The results showed copy number alterations (CNA) of PTEN (76%), PIK3AP1 and CHUK (75% each), EGFR (74%), AKT2 (39%), AKT1 (32%), AKT3 (19%) and GSK3β (18%). The highest number of CNA had glioblastomas with alterations in EGFR, PIK3AP1, and PTEN in 89%, CHUK in 88%, and AKT2 in 43%. The Kruskal-Wallis test showed a significant difference in the methylation and expression of the mRNA of the tested genes between individual grades. The correlation of the results suggests that AKT1, AKT2, EGFR, and PIK3AP1 behave like oncogenes, while AKT3, CHUK, GSK3β, and PTEN act like tumor suppressors. The results contribute to the knowledge of molecular differences between pathohistological types of gliomas and may serve for better classification and treatment methods improvement

In silico analysis of genetic, transcription, epigenetic and protein changes of EGFR-PI3K-AKT-mTOR signaling pathway participants in diffuse gliomas of the brain

Difuzni gliomi heterogena su skupina tumora s agresivnim biološkim ponašanjem. Unatoč novim molekularnim saznanjima razlike između patohistoloških tipova su nedovoljno istražene. U ovoj in silico analizi istraživali smo uloge 8 gena, sudionika signalizacije EGFR-PI3K-AKT-mTOR, u gliomima mozga. Analiza AKT1, AKT2, AKT3, CHUK, GSK3β, EGFR, PTEN i PIK3AP1 napravljena je korištenjem podataka javno dostupne baze cBioPortal za tumorsku genomiku i transkriptomiku. Genske, transkripcijske, epigenetičke te proteinske promjene obrađene su na 751 uzorku (62 difuzna astrocitoma, 129 anaplastičnih astrocitoma te 560 glioblastoma). Rezultati su pokazali promjene u broju kopija (CNA od engl. copy number alteration) gena PTEN (76%), PIK3AP1 i CHUK (75% svaki), EGFR (74%), AKT2 (39%), AKT1 (32%), AKT3 (19%) te GSK3β (18%). Učestalost promjena razlikovala se između gradusa. Najveći broj CNA imali su glioblastomi u kojima su EGFR, PIK3AP1 i PTEN bili promijenjeni u 89%, CHUK u 88%, a AKT2 u 43% analiziranih uzoraka. Kruskal-Wallis test pokazao je značajnu razliku u metilaciji i ekspresiji mRNA ispitivanih gena između pojedinih gradusa. Korelacija rezultata sugerira da se geni AKT1, AKT2, EGFR i PIK3AP1 ponašaju kao onkogeni, a geni AKT3, CHUK, GSK3β i PTEN poput tumor supresora. Rezultati doprinose saznanjima o molekularnim razlikama između patohistoloških tipova glioma te mogu poslužiti za bolju klasifikaciju i poboljšanje metoda liječenja.Diffuse gliomas are a heterogeneous group of tumors with aggressive biological behavior. Despite new molecular findings, the differences between pathohistological types need to be explained better. In this in silico analysis, we investigated participants of EGFR-PI3K-AKT-mTOR signaling in brain gliomas. The analysis of AKT1, AKT2, AKT3, CHUK, GSK3β, EGFR, PTEN, and PIK3AP1 was performed using data from the publicly available cbBioPortal database. 751 samples (62 diffuse astrocytoma, 129 anaplastic astrocytoma and 560 glioblastomas) revealed changes at genetic, transcriptome, epigenome, and protein levels. The results showed copy number alterations (CNA) of PTEN (76%), PIK3AP1 and CHUK (75% each), EGFR (74%), AKT2 (39%), AKT1 (32%), AKT3 (19%) and GSK3β (18%). The highest number of CNA had glioblastomas with alterations in EGFR, PIK3AP1, and PTEN in 89%, CHUK in 88%, and AKT2 in 43%. The Kruskal-Wallis test showed a significant difference in the methylation and expression of the mRNA of the tested genes between individual grades. The correlation of the results suggests that AKT1, AKT2, EGFR, and PIK3AP1 behave like oncogenes, while AKT3, CHUK, GSK3β, and PTEN act like tumor suppressors. The results contribute to the knowledge of molecular differences between pathohistological types of gliomas and may serve for better classification and treatment methods improvement

In silico analysis of genetic, transcription, epigenetic and protein changes of EGFR-PI3K-AKT-mTOR signaling pathway participants in diffuse gliomas of the brain

Difuzni gliomi heterogena su skupina tumora s agresivnim biološkim ponašanjem. Unatoč novim molekularnim saznanjima razlike između patohistoloških tipova su nedovoljno istražene. U ovoj in silico analizi istraživali smo uloge 8 gena, sudionika signalizacije EGFR-PI3K-AKT-mTOR, u gliomima mozga. Analiza AKT1, AKT2, AKT3, CHUK, GSK3β, EGFR, PTEN i PIK3AP1 napravljena je korištenjem podataka javno dostupne baze cBioPortal za tumorsku genomiku i transkriptomiku. Genske, transkripcijske, epigenetičke te proteinske promjene obrađene su na 751 uzorku (62 difuzna astrocitoma, 129 anaplastičnih astrocitoma te 560 glioblastoma). Rezultati su pokazali promjene u broju kopija (CNA od engl. copy number alteration) gena PTEN (76%), PIK3AP1 i CHUK (75% svaki), EGFR (74%), AKT2 (39%), AKT1 (32%), AKT3 (19%) te GSK3β (18%). Učestalost promjena razlikovala se između gradusa. Najveći broj CNA imali su glioblastomi u kojima su EGFR, PIK3AP1 i PTEN bili promijenjeni u 89%, CHUK u 88%, a AKT2 u 43% analiziranih uzoraka. Kruskal-Wallis test pokazao je značajnu razliku u metilaciji i ekspresiji mRNA ispitivanih gena između pojedinih gradusa. Korelacija rezultata sugerira da se geni AKT1, AKT2, EGFR i PIK3AP1 ponašaju kao onkogeni, a geni AKT3, CHUK, GSK3β i PTEN poput tumor supresora. Rezultati doprinose saznanjima o molekularnim razlikama između patohistoloških tipova glioma te mogu poslužiti za bolju klasifikaciju i poboljšanje metoda liječenja.Diffuse gliomas are a heterogeneous group of tumors with aggressive biological behavior. Despite new molecular findings, the differences between pathohistological types need to be explained better. In this in silico analysis, we investigated participants of EGFR-PI3K-AKT-mTOR signaling in brain gliomas. The analysis of AKT1, AKT2, AKT3, CHUK, GSK3β, EGFR, PTEN, and PIK3AP1 was performed using data from the publicly available cbBioPortal database. 751 samples (62 diffuse astrocytoma, 129 anaplastic astrocytoma and 560 glioblastomas) revealed changes at genetic, transcriptome, epigenome, and protein levels. The results showed copy number alterations (CNA) of PTEN (76%), PIK3AP1 and CHUK (75% each), EGFR (74%), AKT2 (39%), AKT1 (32%), AKT3 (19%) and GSK3β (18%). The highest number of CNA had glioblastomas with alterations in EGFR, PIK3AP1, and PTEN in 89%, CHUK in 88%, and AKT2 in 43%. The Kruskal-Wallis test showed a significant difference in the methylation and expression of the mRNA of the tested genes between individual grades. The correlation of the results suggests that AKT1, AKT2, EGFR, and PIK3AP1 behave like oncogenes, while AKT3, CHUK, GSK3β, and PTEN act like tumor suppressors. The results contribute to the knowledge of molecular differences between pathohistological types of gliomas and may serve for better classification and treatment methods improvement

The future of whole genome sequencing in pediatrics

Sekvenciranje cijeloga genoma (eng. Whole genome sequencing – WGS) postaje sve zastupljeniji genetički dijagnostički test u svakodnevnoj kliničkoj praksi. Inicijativa za medicinski genom (eng. Medical Genome Initiative – MGI), prepoznala je WGS kao prioritetnu dijagnostičku metodu za otkrivanje rijetkih genetskih bolesti. Jedna od ključnih prednosti WGS-a u odnosu na sekvenciranje cijelog egzoma (eng. Whole exome sequencing – WES) jest mogućnost analize nekodirajućih dijelova genoma, koji čine oko 98,5% naše DNA, a sadrže ponavljajuće sekvence, sekvence koje kodiraju za nekodirajuće molekule RNA, te brojne regulatorne elemenate ključne za kontrolu genske ekspresije. Primjena WGS-a ima značajan potencijal u pedijatriji i budućnost je dijagnostike genetskih bolesti u djece. Implementacija WGS-a u rutinsku pedijatrijsku praksu pruža nove mogućnosti za razvoj personalizirane medicine i poboljšanje zdravlja dječje populacije, uključujući i preventivno djelovanje radi sprječavanja razvoja multifaktorijalnih bolesti poput dijabetesa, astme i pretilosti. U farmakogenomici, WGS omogućuje personalizirano doziranje lijekova na temelju genetičkog profila, smanjujući nuspojave i povećavajući učinkovitost terapije. U području dječje onkologije, WGS omogućuje, pravodobnu dijagnostiku, personaliziranu terapiju i praćenje napredovanja maligne bolesti. Kontinuirani razvoj tehnologije sekvenciranja genoma i smanjenje troškova omogućit će sve veću dostupnost i primjenu WGS-a u svakodnevnoj kliničkoj praksi te otvoriti nove mogućnosti za individualiziranu medicinu i poboljšanje zdravlja dječje populacije.Whole Genome Sequencing (WGS) is becoming a genetic diagnostic test of choice in everyday clinical practice. The Medical Genome Initiative (MGI) has recognized WGS as a priority diagnostic method for detecting rare genetic diseases. One key advantage of WGS over Whole Exome Sequencing (WES) is its ability to analyze non-coding regions of the genome, which make up approximately 98.5% of our DNA. These regions contain repetitive sequences, sequences that encode non-coding RNA molecules, and numerous regulatory elements crucial for controlling gene expression. The application of WGS holds significant potential in pediatrics and represents the future of genetic disease diagnosis in children. Implementing WGS into routine pediatric practice offers new possibilities for personalized medicine and improving the health of the pediatric population, including preventive interventions to avoid the development of multifactorial diseases such as diabetes and obesity. In pharmacogenomics, WGS enables personalized drug dosing based on a person’s genetic profile, reducing side effects and increasing treatment effectiveness. In the field of pediatric oncology, WGS allows for personalized therapy and monitoring of tumor progression. Continued advancements in genome sequencing technology and cost reduction will increase the availability and application of WGS in clinical practice, opening new avenues for individualized medicine and enhancing the health of the pediatric population

TWIST1 upregulation affects E-cadherin expression in brain metastases

Purpose: E-cadherin is a calcium-dependent glycoprotein whose main role is cell-cell adhesion. Its transcriptional repressor TWIST1 is a basic helix-loop-helix (bHLH) protein that participates in gastrulation and formation of mesodermal tissues during embryogenesis. In adult tissues, the high expression of TWIST1 induces the epithelial-mesenchymal transition (EMT)-a process in which cells become motile and able to metastasize. In this paper, we investigated the involvement of E-cadherin and TWIST1 in the carcinogenesis of brain metastases originating from two different primary sites-breast and lung. ----- Methods: The localization and expression of E-cadherin and its transcriptional repressor TWIST1 were investigated using a DAB-labeled streptavidin-horseradish peroxidase immunohistochemical reaction and specific monoclonal antibodies against TWIST1 and E-cadherin. Image J software was used for semi-quantitative analysis while H-score served for statistical evaluations. ----- Results: Immunohistochemistry showed that the expression of E-cadherin was downregulated in 85.7% of brain metastases, while at the same time, 82.2% of them showed upregulated TWIST1. Statistical analysis confirmed a significant negative correlation between expressions of TWIST1 and E-cadherin (p = 0.001). When the brain metastases expression levels were compared to primary breast tumors in corresponding patients, E-cadherin showed higher expression in primary pairs compared to corresponding metastases. Consistent to its role, TWIST1 was downregulated in all primary tumor samples in comparison to corresponding metastases pairs (p = 0.034). ----- Conclusion: This research provides valuable data regarding molecular events involving two EMT key components that could give directions for new possibilities for brain metastases diagnosis and treatment