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Laryngeal Squamous Cell Carcinoma Is Characterized by a Stronger Expression of Nectin-4 Compared to Nectin-2
Nectin-2 and Nectin-4 are cell adhesion molecules associated with the progression of various cancers. The main goal of this pilot study was to evaluate the expression patterns of Nectin-2 and Nectin-4 in laryngeal squamous cell carcinoma (LSCC). A retrospective study was conducted on tissue microarray (TMA) samples derived from 31 patients who underwent total laryngectomy. The findings revealed heterogenous expression of both Nectin-2 and Nectin-4 in tumor cells and surrounding stroma, with Nectin-4 expression being significantly higher than Nectin-2 expression. Specifically, 74% of cases showed weak cytoplasmic staining for Nectin-2, while 41.93% exhibited strong cytoplasmic staining for Nectin-4. Both Nectin-2 and Nectin-4 expressions were more pronounced at the invasive tumor margins. Although no significant differences in Nectin-4 expression were observed across tumor grades (W = 83.500; z = −0.463; p = 0.658), differences in expression patterns were noted. Well-differentiated tumors (Grade 1), 80.65% of cases, showed predominantly membranous Nectin-4 staining, including in squamous epithelial cells of the mucosal surface. Conversely, in less-differentiated tumors (Grade 2 and 3), a shift toward cytoplasmic staining was evident. Specifically, 74.19% of Grade 2 tumors and 100% of Grade 3 tumors showed a predominant cytoplasmic localization of Nectin-4. This transition from membranous to cytoplasmic localization was also evident in the progression from normal superficial epithelium to malignant tissue. These observations suggest that alterations in the expression and subcellular localization of Nectin-4 may be associated with carcinogenesis and could serve as potential markers for the assessment of precancerous lesions and the aggressiveness of laryngeal tumors
Authenticity assessment of honeydew honey based on phytochemical profile
Considering the health-beneficial properties of honeydew honey and difficulties in its authenticity assessment, a high-performance thin-layer chromatography (HPTLC) fingerprint method in combination with multivariate analysis was developed, in order to relate phenolic profiles of selected honey samples to their verified botanical origin and biological activity. The HPTLC chromatograms were obtained using two derivatization reagents, vanillin-sulfuric acid and 2,2-diphenyl-1-picrylhydrazyl (DPPH) solution. Phenolic profiles of samples indicated the uniformity within each honey variety, but also variability among different botanical origin. Chemometric evaluation, including principal component analysis and partial least squares discriminant analysis, hyphenated with chromatographic method provided a discriminative and predictive methodology for classification of Hungarian oak, Evergreen oak, Montpellier maple and Silver fir honey samples. The analysis highlighted the significance of specific phenolic compounds (e.g., RF = 0.31, 0.41, 0.51) for distinguishing the samples, underscoring the potential for accurate botanical authentication of samples, particularly Hungarian oak honey, based on its chemical profile. The HPTLC-DPPH method demonstrated a high potential for differentiating samples based on antioxidant activity, offering an efficient alternative to other techniques for antioxidant activity determination. PLS-DA models successfully predicted the botanical origin of Quercus spp., Evergreen oak and Hungarian oak. This approach can be useful for ensuring the quality control of honeydew honey products, providing an efficient and resource-saving alternative to more advanced analytical techniques. Additionally, caffeic acid emerged as the most potent antioxidant across the selected honeydew honey varieties. This highlights the potential of caffeic acid as a key bioactive compound contributing to the health-promoting properties of honeydew honey
Kako školski uspjeh, uhranjenost i izvannastavne aktivnosti oblikuju mentalno zdravlje mladih: Istraživanje među učenicima na kraju osnovnoškolskog obrazovanja u Primorsko-goranskoj županiji
Uvod: Adolescencija je ključno razdoblje intenzivnog razvoja i transformacije. U ovom životnom
razdoblju mladi prolaze kroz tjelesne, emocionalne i kognitivne promjene koje značajno utječu na njihovo
mentalno zdravlje. Školski uspjeh, izvanškolske aktivnosti, tjelesna masa i mentalno zdravlje ključni su
aspekti adolescentskog iskustva. Razumijevanje njihovih međusobnih odnosa važno je za cjelokupnu brigu
o razvoju adolescenata.
Cilj: Cilj nam je bio ispitati odnos školskog uspjeha, sportskih izvanškolskih aktivnosti, indeksa tjelesne
mase i mentalnog zdravlja kod učenika osmih razreda osnovnih škola.
Ispitanici i metode: U istraživanju je sudjelovalo 210 učenika osmih razreda iz šest osnovnih škola u
Primorsko-goranskoj županiji. Podaci su prikupljeni iz preventivnog zdravstvenog kartona Odjela za
školsku i adolescentnu medicinu Nastavnog zavoda za javno zdravstvo Primorsko-goranske županije
tijekom redovnih sistematskih pregleda učenika osmih razreda. Emocionalnu uznemirenost mjerili smo YP
upitnikom.
Rezultati: Rezultati pokazuju da je ukupna emocionalna uznemirenost niska, s prosjekom 8,13% kod
djevojčica, odnosno 5,39% kod dječaka. Učenici s nižom razinom emocionalne uznemirenosti postižu bolji
školski uspjeh i češće sudjeluju u izvanškolskim aktivnostima. Učenici s višim indeksom tjelesne mase
imaju višu emocionalnu uznemirenost. Ženski spol i niži školski uspjeh značajni su prediktori više
emocionalne uznemirenosti, dok je sudjelovanje u izvanškolskim aktivnostima na granici statističke
značajnosti, a indeks tjelesne mase nije statistički značajan.
Zaključak: U razumijevanju složenih odnosa varijabli koje su ključne za pravilan tjelesni, emocionalni
i kognitivni razvoj, te mentalno blagostanje adolescenta, trebamo stvarati sigurno školsko, društveno i
obiteljsko okruženje. Tek kroz čvrstu suradnju s obiteljima, školskim savjetnicima i stručnjacima za
mentalno zdravlje, mladima možemo pružiti podršku i razumijevanje koje im je potrebno. Takav tip
savjetovališta već godinama postoji u ambulantama školske medicine Primorsko-goranske županije. Kao
što im samo ime kaže, Savjetovališta otvorenih vrata su centri koji su besplatni, lako dostupni mladima, te
ekipirani profesionalcima raznih specijalnosti. Ovo je istraživanje pokazalo da imamo potrebu za njegovim
postojanjem i još intenzivnijim radom
Epithelial Remodelling in Myopia After Keratorefractive Lenticule Extraction
Introduction: We analyzed longitudinal epithelial changes after the treatment of myopia with keratorefractive lenticule extraction (KLEx) and the zonal change in epithelial thickness up to 12 months after SmartSight for myopic astigmatism with the SCHWIND ATOS femtosecond laser. Methods: We used anterior segment optical coherence tomography (AS-OCT) data and analyzed changes in the epithelium after treatment to ascertain how much epithelium hyperplasia occurred after KLEx. Data from 80 eyes treated with SmartSight, with a complete follow-up from postoperative day 1 (POD1) to 12 months postoperative, were used. The mean age of the patients was 29 ± 6 years with a mean spherical equivalent (SEQ) of − 4.72 ± 1.97 diopters (D) (− 1.25 to − 9.88 D) and a mean magnitude of refractive astigmatism of 0.90 ± 0.89 D. Preoperative central epithelial thickness was from 46 to 67 µm. Results: Postoperative central epithelial thickness at 12-month follow-up was 3 ± 5 µm thicker than preoperatively. The other epithelial zones (nasal, superior, temporal, inferior) thickened by + 4 ± 4 µm. The epithelial change showed larger variability at POD1 and stabilized from 1 week onwards. Postoperatively, the change in epithelium was not different for the different zones, and it did not correlate with the achieved refractive changes for any zone at any time point. Conclusions: The changes in epithelial thickness after KLEx for moderate myopia with SmartSight were minimal, indicating a low level of epithelial hyperplasia without resembling a regression-inducing lentoid. Findings suggest that KLEx with SCHWIND ATOS has a subtle impact on the epithelial thickness (with postoperative epithelium becoming slightly thicker). However, the differences remain below any clinical relevance
HPMA-based nitroxide radical containing nanoparticles with controlled radical release: Detailed physico-chemical characterization
This research focuses on the measurement of the release of nitroxide radicals from polymer-based nanoparticles by electron paramagnetic resonance (EPR) and potentiometric titration techniques. Nitroxide radicals such as 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) are known to modulate oxidative stress by scavenging reactive oxygen species that cause cell damage. It was also found that these biologically active radicals can inhibit tumor growth by inducing apoptosis in cancer cells. Nitroxide radicals, however, cannot be effectively used due to their non-specific accumulation in normal tissue and quick elimination from the body. To address these challenges, we developed pH-responsive nanoparticles based on self-assembly of amphiphilic N-(2-hydroxypropyl)meth- acrylamide (HPMA)-based copolymers containing TEMPO radicals, covalently attached to the hydrophilic shell by a pH-sensitive hydrazone bond, and compared with pH-unresponsive nanoparticles, where the TEMPO radicals were bound by a physiologically stable amide bond. We thoroughly investigated the nitroxide radicals release from nanoparticles by EPR and potentiometric titration for the first time. TEMPO radicals were almost completely released from the pH-responsive nanoparticles within three hours at pH = 5 at 37 degrees C, which corresponds to tumor tissue, while only quite slow release of radicals was observed at physiological pH within 24 h. The results show that nitroxide radicals containing HPMA-based nanoparticles could be potentially used either for tumor visualization or as smart prodrugs to enhance nitroxide radicals' therapeutic efficacy and safety
Special Issue “Brain Injury: New Insights into Mechanisms and Future Promising Treatments”
This Special Issue of Biomedicines presents 12 published, peer-reviewed articles on the theme of “Brain Injury: New Insights into Mechanisms and Future Promising Treatments”, including 10 original research papers and 2 reviews covering the topics related to the pathophysiology of acquired central nervous system (CNS) injuries, as well as biomarker discovery, diagnosis, and potential pharmacological and non-pharmacological approaches in the treatment of these disorders [...
The Risk of Type 2 Diabetes Mellitus: Cardiorenometabolic Syndrome and Its Components—A Call to Action
Cardiorenometabolic syndrome, a constellation of interrelated risk factors including insulin resistance, central obesity, dyslipidemia, and hypertension, is rapidly becoming one of the defining global health challenges of our time [...
Bridging Clinical Outcomes and Cost‐Effectiveness: The Role of Real‐World Data in Cystic Fibrosis Therapy
Increased burden of rare variants in GWAS associated genes in familial multiple sclerosis
Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease affecting the central nervous system with many known genetic risk factors. Although genome-wide association studies (GWAS) have identified common genetic variants with small effects associated with MS, the role of rare variants with large effects in MS aetiology remains underexplored. We hypothesized that rare variants in MS-associated genes from GWAS studies (GWAS-associated genes) are more likely to contribute to familial MS (FMS) risk than to sporadic MS (SMS). Therefore, we aimed to assess the burden of rare, predicted pathogenic (RPP) variants in GWAS-associated genes in FMS and SMS patients compared to controls. Rare genetic variants in 111 GWAS-associated genes were assessed in 87 FMS, 89 SMS and 3866 control cases. We demonstrate that RPP variants were significantly overrepresented in the FMS cohort whereas their frequency was not increased in the SMS cohort compared to controls (p-values 5.27 × 10− 74 and 1.00, respectively). Six genes (ALPK2, ANKRD55, INTS8, IQCB1, JADE2, and MALT1) significantly contributed to the burden of RPP in the FMS group. We conclude that rare variants in genes identified by GWAS might contribute to the genetic predisposition of familial MS patient
A review of the most commonly used dietary supplements for supporting female fertility
Plodnost žene ovisi o brojnim čimbenicima, uključujući hormonalnu homeostazu, kvalitetu jajnih stanica, opće zdravstveno stanje i način života. Dodaci prehrani postaju sve češće korišteni u pokušajima poboljšanja ženske plodnosti, kako kod prirodnog začeća, tako i u medicinski pomognutim postupcima. Posebno se ističu suplementi kao što su folna kiselina, dehidroepiandrosteron, koenzim Q10, inozitol, vitamin D i omega-3 masne kiseline. Smatra se kako oni djeluju povoljno na poboljšanje kvalitete jajnih stanica, regulaciju hormona, uspješniju implantaciju embrija i na podršku trudnoće.
Dok za zdravstvene prednosti folne kiseline postoje znanstveni dokazi, za ostale dodatke prehrani rezultati istraživanja su obećavajući, no još uvijek nedovoljno potvrđeni. Uloga dodataka prehrani posebno dolazi do izražaja kod stanja poput sindroma policističnih jajnika, smanjene ovarijske rezerve i kod žena koje se podvrgavaju postupcima in vitro oplodnje.
Cilj korištenja suplemenata nije zamjena medicinskim tretmanima, već njihova nadopuna i individualna prilagodba kako bi se povećale šanse za uspješnu i zdravu trudnoću.Female fertility depends on numerous factors, including hormonal homeostasis, oocyte quality, overall health status and lifestyle. Dietary supplements are increasingly used in attempts to improve female fertility, both in natural conception and in medically assisted reproductive procedures. Supplements such as folic acid, dehydroepiandrosterone, coenzyme Q10, inositol, vitamin D and omega-3 fatty acids are especially highlighted. They are believed to have a positive effect on improving oocyte quality, hormone regulation, successful embryo implantation, and pregnancy support.
While there is scientific evidence supporting the health benefits of folic acid, research results for other dietary supplements are promising but still insufficiently confirmed. The role of dietary supplements is particularly emphasized in conditions such as polycystic ovary syndrome, diminished ovarian reserve, and in women undergoing in vitro fertilization procedures.
The goal of using supplements is not to replace medical treatments but to complement them and allow individual adaptation to increase the chances of a successful and healthy pregnancy