Veterinary medicine - Repository of PHD, master's thesis
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A comparative cross-sectional study of the impact of COVID-19 pandemic on obstetrics and gynecology admissions in Croatia
No full textBackground: The COVID-19 pandemic placed unprecedented pressure on healthcare systems worldwide and altered patients' perceptions of the system's ability to protect them from virus transmission. One significant consequence was a marked decline in hospital activity, a trend observed globally. This study aims to evaluate the impact of COVID-19 on hospitalization rates among patients with gynecological disorders in Croatia. It compares the number of patients treated surgically vs. conservatively before the pandemic (2017-2019) and during the pandemic (2020-2022) using the Diagnostic-Related Group (DRG) patient classification system. The DRG system is designed to group patients based on similar clinical conditions, complexity, and resource utilization. Hospital activity categorized by DRGs was analyzed to assess the impact of the COVID-19 pandemic on case volumes within DRG groups associated with gynecological and obstetric disorders.
Materials and methods: We conducted a comparative descriptive cross sectional study of the pre-post type according to STROBE guidelines to determine the impact of COVID-19 pandemic on hospital admission rates for patients with conditions associated with illnesses and abnormalities of the female reproductive system, as well as pregnancy, delivery, and the puerperium. The publicly available data collected by Croatian Institute of Public Health (CIPH) and the Croatian Health Insurance Fund (CHIF) were the main data source for this study. All gynecological hospital admissions in Croatia were grouped based on the Australian Refined Diagnosis Related Groups (AR-DRGs) and analyzed over two time periods: before (2017-2019) and during the pandemic (2020-2022).
Results: The average number of gynecological patients in all hospitals during the pandemic was 62,257 compared to pre-pandemic when the average number of patients was 71,519, a decrease of 15.5%. The results show a 10.56% decrease in the total number of non-surgical admissions and 12.8% decrease of surgical admissions across the hospital network during the pandemic (2020-2022).
Conclusion: The COVID-19 pandemic led to a significant decline in inpatient treatments in gynecology and obstetrics departments in Croatia. Our findings highlight the need for obstetrics and gynecology practitioners to develop innovative strategies to maintain or enhance patient access to appropriate care while ensuring stringent infection prevention measures for both patients and healthcare personnel. Furthermore, investing in healthcare system resilience is crucial to maintaining core functions during future crises. The lessons learned from the COVID-19 pandemic provide a valuable opportunity to fortify healthcare systems and must not be ignored
Short-Term In Vitro Exposure of Human Blood to 5G Network Frequencies: Do Sex and Frequency Additionally Affect Erythrocyte Morphometry?
No full textBackground/Objectives: This study assessed the effects of 5G radiofrequency electromagnetic radiation (RF-EMR) at different frequencies (700 MHz, 2500 MHz, 3500 MHz) on the complete blood count (CBC), erythrocyte morphometry, and platelet activation after the short-term in vitro exposure of human blood. Methods: Blood samples from 30 healthy volunteers (15 men and 15 women, aged 25–40 years old) were collected at three intervals (14 days apart). For each collection, four tubes of blood were drawn per volunteer—two experimental and two controls. Experimental samples were exposed to 5G RF-EMR for 2 h at room temperature using a half-cone gigahertz transverse electromagnetic cell. The CBC was analysed via a haematology analyser, the erythrocyte morphometry was analysed using the SFORM program, and platelet activation was analysed via flow cytometry. Results: The CBC and platelet activation showed no significant differences between the experimental and control samples. However, the erythrocyte morphometry exhibited notable changes. At 700 MHz, the erythrocyte size, contour, and membrane roughness increased significantly for both sexes, with women’s cells showing greater sensitivity. At 2500 MHz, women exhibited an increased contour index and a decreased solidity and form factor. At 3500 MHz, women showed an increased contour index and outline but a decreased solidity, elongation, and form factor. Cluster analysis identified two erythrocyte subpopulations: smaller, rounder cells with smooth membranes and larger cells with rougher membranes. Conclusions: These results indicate that 5G RF-EMR exposure significantly alters erythrocyte morphometry. The strongest effects were observed at 700 MHz, where men exhibited greater membrane roughness, and women showed larger and rounder erythrocytes. These findings suggest that short-term in vitro 5G RF-EMR exposure disrupts the cytoskeleton, increasing membrane permeability and deformability
Heavily pretreated patient with nodal marginal zone lymphoma successfully treated with mosunetuzumab
No full textRegenerative effect of oral mucosa stem cells on hypoxia damaged neurons in vitro
No full textRegenerativna medicina je moderna disciplina koja jedan dio svojih uspjeha temelji na terapijskom učinku matičnih stanica i molekula koje one izlučuju. Ipak, mnoge vrste matičnih stanica se teško dobivaju ili je njihova primjena povezana s etičkim nedoumicama, pa je pronalaženje lako dostupnih izvora stanica važno za daljnji napredak. Ovo istraživanje je opisalo novu populaciju matičnih stanica, dobivenu biopsijom oralne sluznice, nazvanih ljudske matične stanice oralne sluznice (hOMSC). Nakon što smo usporedbom različitih protokola uspostavili postupak kojim dobivamo dovoljnu količinu homogenih stanica koje su
diferencijacijom oblikovale strukture tipične za nezrele ektodermalne stanice, testiranjem različitih biljega smo ovu populaciju definirali kao značajno pozitivnu na nestin i CD166, uz mjerljivu prisutnost OCT4, SOX2, CD90, CD40 i SNAIL2. Testiranje njihove otpornosti na anoksiju je otkrilo kako oralne matične stanice bolje preživljavaju u odnosu na iPSC. Također, hOMSC izlučuju regenerativne molekule BDNF, VEGF i NGF što je ovisilo o duljini kontakta s neuronima. Isto tako je pokazano kako oralne matične stanice povećavaju preživljenje ljudskih neurona oštećenih manjkom kisika. Sve navedeno ukazuje kako je ovo istraživanje uspostavilo protokol dobivanje stanične populacije iz razmjerno lako dostupnog izvora koja ima značajan potencijal u liječenju ishemijski oštećenog živčanog tkiva.Regenerative medicine is a contemporary discipline that relies part of its success on the therapeutic effects of stem cells and the molecules they secrete. However, many types of stem cells are difficult to obtain or are associated with ethical concerns, making the identification of easily accessible cell sources crucial for further advancement. This study describes a novel population of stem cells, obtained through oral mucosa biopsy, referred to as human oral mucosa stem cells (hOMSC). By comparing different protocols, we established a method to obtain enough of homogeneous cells that differentiate into structures typical of immature ectodermal cells. Through marker analysis, this population was characterized as significantly positive for nestin and CD166 with a measurable expression of OCT4, SOX2, CD90, CD40, and SNAIL2. Testing their resistance to anoxia revealed that oral stem cells exhibit substantial resilience under extreme conditions compared to iPSC. Additionally, hOMSC secretes essential regenerative molecules: BDNF, VEGF, and NGF. The duration of contact with neurons modulates the secretion levels of these molecules. It was also demonstrated that oral stem cells enhance the survival of human neurons subjected to hypoxic damage. These findings indicate that this study has established a protocol for deriving a cell population from an easily accessible source with significant potential for treating ischemic neural tissue damage
Nucelotide polymorphism rs531564 of pri-miR-124 gene in patients with primary sclerosing cholangitis and inflammatory bowel disease
No full textUpalne bolesti crijeva (UBC) kronične su imunosno posredovane bolesti genski predisponiranih osoba, čija etiopatogeneza nije potpuno razjašnjena. Posebno se ističe fenotip UBC-a kod pacijenata s primarnim sklerozirajućim kolangitisom (PSC). UK i CB u tih bolesnika dominantno zahvaćaju kolon, karakteristično su blažeg tijeka, ali uz povišen rizik razvoja kolorektalnog karcinoma, a i drugih malignih bolesti. Rezultati naše kohorte bolesnika su u skladu s dosad publiciranim podacima u literaturi.
Smatra se da miR imaju važnu ulogu u navedenoj patogenezi. Uloga miR-124 posebno je istražena, pokazujući važnost u održavanju integriteta crijevne barijere i regulaciji proinflamatornih citokina, a SNP (rs531564) gena povezan je s njezinom ekspresijom.
Cilj ovog ispitivanja bio je prvi put u ovoj populaciji analizirati učestalost genotipa navedenog SNP-a.
Nismo uspjeli pokazati značajne razlike u genotipu između ispitivane (UBC/PSC) i kontrolne skupine (UBC). Genotip GG numerički je učestaliji u bolesnika s UBC-om u odnosu na PSC, ali razlike nisu bile statistički značajne. Nije pronađena značajna razlika po genotipu za kliničke ili demografske varijable osim za bolesnike s UK-om, gdje su ispitanici s genotipom GC bili značajno mlađi te su mlađi započinjali biološku terapiju u odnosu na ispitanike s genotipom GG. Potrebna su daljnja, multicentrična istraživanja na većem uzorku kako bi se potvrdili ovi nalazi.Inflammatory bowel diseases (IBD) are chronic, immunologically mediated diseases of genetically predisposed individuals, whose etiopathogenesis is not fully understood. The phenotype of IBD in patients with primary sclerosing cholangitis (PSC) is particularly notable. Ulcerative colitis (UC) and Crohn's disease (CD) in these patients predominantly affect the colon and are characteristically milder in course but with an increased risk of developing colorectal cancer as well as other malignancies. The results from our cohort of patients are consistent with previously published data in the literature.
It is believed that microRNAs (miRNAs) play an important role in the aforementioned pathogenesis. The role of miR-124 has been particularly studied, showing its importance in maintaining intestinal barrier integrity and regulating pro-inflammatory cytokines, with the SNP (rs531564) gene being associated with its expression.
The aim of this study was to analyze, for the first time in this population, the frequency of genotypes of the mentioned SNP.
We did not show significant differences in genotype between the study group (IBD/PSC) and the control group (IBD). The GG genotype was numerically more prevalent in patients with IBD compared to PSC, but the differences were not statistically significant. No significant difference was found by genotype for clinical or demographic variables except for UC patients, where participants with the GC genotype were significantly younger and started biological therapy earlier compared to the GG genotype. Further multicentric studies on larger samples are needed to confirm these findings
Controversies in treating nutcracker syndrome
No full textNutcracker syndrome (NCS) is a relatively uncommon vascular condition characterized by compression of the left renal vein (LRV), resulting in a variable spectrum of nonspecific symptoms, including hematuria, flank pain, varicocele, and pelvic congestion syndrome. NCS can be classified into anterior and posterior types regarding the origin of LRV compression: anterior NCS occurs when LRV is compressed between the aorta and superior mesenteric artery, whereas posterior NCS involves LRV compression between the aorta and the spine. Despite advancements in diagnostic modalities, including Doppler ultrasound, computed tomography, magnetic resonance imaging, and invasive techniques like phlebography, there is still no globally accepted diagnostic algorithm, leading to inconsistencies in diagnosis. Moreover, due to the lack of standardized treatment guidelines, the optimal management of anterior NCS remains a topic of debate. While conservative management is usually recommended in the pediatric population, invasive treatments—including surgical options like LRV transposition and renal autotransplantation, as well as interventional radiology procedures like stenting, present challenges such as stent migration, restenosis, and long-term material durability. Nevertheless, the emergence of 3D-printed stents offers potential improvements in patient-specific treatment, particularly in the pediatric population, yet their clinical efficacy and safety remain under investigation. This brief communication addresses the current discussions regarding anterior NCS management, emphasizing the need for standardized diagnostic algorithms, a multidisciplinary approach, and continued technological advancements to refine treatment possibilities and strategies. Further research is critical to resolve these controversies and establish a consensus on best practices
Comparable outcomes after busulfan- or treosulfan-based conditioning for allo-HSCT in children with ALL: results of FORUM
No full textThe superiority of total body irradiation (TBI)-based vs chemotherapy conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukemia (ALL) has been established in the international, prospective phase-3 FORUM study, randomizing 417 patients aged 4-18 years in complete remission (CR), who received allo-HSCT from HLA-matched sibling or unrelated donors. Because of the unavailability of TBI in some regions and to accommodate individual contraindications, this study reports the prespecified comparison of outcomes of patients receiving busulfan (BU)- or treosulfan (TREO)-based regimens from 2013 to 2018. Overall, 180 and 128 patients received BU/thiotepa (THIO)/fludarabine (FLU) or TREO/THIO/FLU, respectively. Data were analyzed as of February 2023, with a median follow-up of 4.2 years (range, 0.3-9.1). 3-year overall survival was 0.71 (BU, 95% confidence interval [0.64-0.77]) and 0.72 (TREO, [0.63-0.79]) and 3-year event-free survival was 0.60 (BU, [0.53-0.67]) and 0.55 (TREO, [0.46-0.63]). The 3-year cumulative incidence of relapse (BU, 0.31 [0.25-0.38]; TREO, 0.36 [0.27-0.44]); and nonrelapse mortality (BU, 0.08 [0.05-0.13]; TREO, 0.09 [0.05-0.15]) were comparable. One case of fatal veno-occlusive disease occurred in each group. No significant differences in acute and chronic graft-versus-host disease (GVHD) or 3-year GVHD-free and relapse-free survival (BU, 0.48 [0.41-0.55]; TREO, 0.45 [0.37-0.54]) were recorded. Outcomes for patients in first and second CR were similar irrespective of the regimen. In conclusion, BU/THIO/FLU or TREO/THIO/FLU regimens can be an alternative to TBI for patients with ALL aged >4 years with contraindications or lack of access to TB
Epidemiological and Entomological Study After the Possible Re-Emergence of Dengue Fever in Croatia, 2024
No full textAutochthonous dengue cases have been continuously recorded in Europe in the past two decades. The first autochthonous dengue case in Croatia was reported in 2010 on the Pelješac Peninsula, while imported cases were recorded continuously thereafter. In 2024, dengue re-emerged in Croatia. An epidemiological and entomological study was conducted after receiving information on dengue virus (DENV) infection in a German tourist probably acquired on Dugi Otok Island in Croatia in May 2024. Serum samples were collected from 30 residents of the Veli Rat region where the patient had stayed. In addition, mosquitoes were collected in the same area. Human samples were tested for the presence of DENV antibodies (ELISA and IFA) and DENV RNA (RT-qPCR), while mosquito samples were tested for DENV RNA (RT-qPCR). DENV IgM or IgG antibodies were found in 8 serum samples, while no one sample was RT-qPCR positive. No cross-reactivity with flaviviruses was detected in seropositive samples, supporting DENV infection. One patient was classified as a confirmed dengue case (IgG seroconversion in paired serum samples) and five as probable cases (IgM detection in a single serum sample). One additional patient, sampled only once, was IgG seropositive. Two of the seropositive individuals reported fever and rash three weeks before testing. The re-emergence of dengue in Croatia highlights the need for continuous monitoring of DENV circulation in both humans and vectors
Quiescent cells maintain active degradation-mediated protein quality control requiring proteasome, autophagy, and nucleus-vacuole junctions
No full textMany cells spend a major part of their life in quiescence, a reversible state characterized by a distinct cellular organization and metabolism. In glucose-depleted quiescent yeast cells, there is a metabolic shift from glycolysis to mitochondrial respiration, and a large fraction of proteasomes are reorganized into cytoplasmic granules containing disassembled particles. Given these changes, the operation of protein quality control (PQC) in quiescent cells, in particular the reliance on degradation-mediated PQC and the specific pathways involved, remains unclear. By examining model misfolded proteins expressed in glucose-depleted quiescent yeast cells, we found that misfolded proteins are targeted for selective degradation requiring functional 26S proteasomes. This indicates that a significant pool of proteasomes remains active in degrading quality control substrates. Misfolded proteins were degraded in a manner dependent on the E3 ubiquitin ligases Ubr1 and San1, with Ubr1 playing a dominant role. In contrast to exponentially growing cells, the efficient clearance of certain misfolded proteins additionally required intact nucleus-vacuole junctions (NVJ) and Cue5-independent selective autophagy. Our findings suggest that proteasome activity, autophagy, and NVJ-dependent degradation operate in parallel. Together, the data demonstrate that quiescent cells maintain active PQC that relies primarily on selective protein degradation. The necessity of multiple degradation pathways for the removal of misfolded proteins during quiescence underscores the importance of misfolded protein clearance in this cellular state