Veterinary medicine - Repository of PHD, master's thesis
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Healthcare professionals’ perspective on managing the healthcare system in Croatia: a cross-sectional study
No full textAim: To determine Croatian healthcare (HC) professionals' perspectives on HC management and leadership challenges.
Methods: This cross-sectional study, conducted between May and June 2021, enrolled 1179 respondents from both the public and private sector, including medical doctors, nurses, pharmacists, economists, and other HC professionals. Their perspective on various facets of HC management, namely governance, ownership, accountability, financing, and potential for improvement, were investigated using an anonymous online survey.
Results: Most respondents agreed that the system may be allocating resources ineffectively and that political mandates unduly influenced management decisions, impeding accountability. Competencies in organizational and financial experience, along with communication and leadership skills, were deemed fundamental for health care managers. Participants overwhelmingly supported data-driven decision-making, improved education, and the development of leadership skills as key avenues for system enhancement.
Conclusions: The study underscores the need for better financial management and overall governance, in the Croatian HC, offering insights that can inform evidence-based policy decisions and reforms toward a more efficient and accountable HC system
Renal metastasis of gastric cancer caused acute kidney injury which resulted with hemodialysis: case report and literature review
No full textGastric cancer ranks fourth among the most commonly diagnosed cancers, with over a million new cases diagnosed worldwide each year. Acute and chronic kidney damage are common in patients with malignant diseases and are associated with increased risk of complications and mortality. Rarely, acute renal insufficiency may result from bilateral infiltration of renal parenchyma by tumor cells from another organ. We present a case of a patient with clinical suspected gastric cancer and metastases to the kidneys leading to acute renal failure requiring hemodialysis. Despite gastric biopsies, no tumor cells were found, while histopathological examination of enlarged intra-abdominal lymph node biopsy material confirmed adenocarcinoma of signet ring cell originating from the digestive system. Stomach cancer was identified as the most likely primary site after the kidney biopsy was performed. To the best of our knowledge, no case of gastric cancer leading to kidney metastases and acute renal failure requiring renal replacement therapy was yet described. Multidisciplinary collaboration among oncologists, urologists, radiologists, pathologists, and nephrologists is essential for the optimal treatment outcome of these patients, who generally have a poor prognosis
Development of the basic architecture of neocortical circuitry in the human fetus as revealed by the coupling spatiotemporal pattern of synaptogenesis along with microstructure and macroscale in vivo MR imaging
No full textIn humans, a quantifiable number of cortical synapses appears early in fetal life. In this paper, we present a bridge across different scales of resolution and the distribution of synapses across the transient cytoarchitectonic compartments: marginal zone (MZ), cortical plate (CP), subplate (SP), and in vivo MR images. The tissue of somatosensory cortex (7–26 postconceptional weeks (PCW)) was prepared for electron microscopy, and classified synapses with a determined subpial depth were used for creating histograms matched to the histological sections immunoreacted for synaptic markers and aligned to in vivo MR images (1.5 T) of corresponding fetal ages (maternal indication). Two time periods and laminar patterns of synaptogenesis were identified: an early and midfetal two-compartmental distribution (MZ and SP) and a late fetal three-compartmental distribution (CP synaptogenesis). During both periods, a voluminous, synapse-rich SP was visualized on the in vivo MR. Another novel finding concerns the phase of secondary expansion of the SP (13 PCW), where a quantifiable number of synapses appears in the upper SP. This lamina shows a T2 intermediate signal intensity below the low signal CP. In conclusion, the early fetal appearance of synapses shows early differentiation of putative genetic mechanisms underlying the synthesis, transport and assembly of synaptic proteins. “Pioneering” synapses are likely to play a morphogenetic role in constructing of fundamental circuitry architecture due to interaction between neurons. They underlie spontaneous, evoked, and resting state activity prior to ex utero experience. Synapses can also mediate genetic and environmental triggers, adversely altering the development of cortical circuitry and leading to neurodevelopmental disorders
Middle Ear Neuroendocrine Tumor: Case Report of a Tympanic Adenoma
No full textMiddle ear neuroendocrine tumors (MeNETs) are an exceptionally rare occurrence. These benign tumors stem from the tympanic mucosa and can easily be misinterpreted by the clinician and the pathologist. Clinical characteristics, otoscopic findings and medical imaging in these cases are non-specific. We present a case of a 60-year-old male patient with bilateral hearing loss following recent coronavirus disease 2019 disease. Diagnostic work-up revealed a soft tissue neoplasm of the left middle ear. Surgical resection of the tumor mass with implantation of a partial ossicular replacement prosthesis (PORP) was the main modality of treatment. Middle ear neuroendocrine tumors was confirmed through positive immunohistochemistry for neuroendocrine tumor markers. Follow-up magnetic resonance imaging 12 months after the surgery reported no tumor recurrence or significant residual disease with a stable PORP. Our report highlights challenges in diagnosing and treating these rare tumors, while emphasizing surgical resection pitfalls and resulting improvement of quality of life of the patient. We recommend a through followup of patients with unclear soft tissue masses in the middle ear to obtain a definitive diagnosis
Stearoyl-CoA desaturase inhibition is toxic to acute myeloid leukemia displaying high levels of the de novo fatty acid biosynthesis and desaturation
No full textIdentification of specific and therapeutically actionable vulnerabilities, ideally present across multiple mutational backgrounds, is needed to improve acute myeloid leukemia (AML) patients' outcomes. We identify stearoyl-CoA desaturase (SCD), the key enzyme in fatty acid (FA) desaturation, as prognostic of patients' outcomes and, using the clinical-grade inhibitor SSI-4, show that SCD inhibition (SCDi) is a therapeutic vulnerability across multiple AML models in vitro and in vivo. Multiomic analysis demonstrates that SCDi causes lipotoxicity, which induces AML cell death via pleiotropic effects. Sensitivity to SCDi correlates with AML dependency on FA desaturation regardless of mutational profile and is modulated by FA biosynthesis activity. Finally, we show that lipotoxicity increases chemotherapy-induced DNA damage and standard chemotherapy further sensitizes AML cells to SCDi. Our work supports developing FA desaturase inhibitors in AML while stressing the importance of identifying predictive biomarkers of response and biologically validated combination therapies to realize their full therapeutic potential
Serum Concentrations of Chemokines CCL20, CXCL8 and CXCL10 in Relapsing-Remitting Multiple Sclerosis and Their Association with Presence of Antibodies against Epstein–Barr Virus
No full textEpstein–Barr virus (EBV) infection and various chemokines, including CCL20, CXCL8 and CXCL10 are considered to participate in the pathogenesis of multiple sclerosis (MS), and several studies point to a direct regulatory effect of EBV on the expression of these chemokines. In our study we hypothesized that serum concentrations of CCL20, CXCL8 and CXCL0 are induced in patients with relapsing-remitting MS (RRMS) in comparison to healthy individuals, and that they are associated with EBV infection. Serum concentrations of CXCL8 and CXCL10 were lower in RRMS patients in relapse in comparison to healthy controls. Although potential effects of corticosteroid therapy introduced in a subgroup of RRMS patients prior to sampling were excluded by subgroup comparison, this possibility has to be considered while interpreting the results. We found an inverse association between serum concentrations of CXCL8 and anti-Epstein–Barr Virus Nuclear Antigen (EBNA) IgG and decreased expression of CXCL8 in peripheral blood mononuclear cells (PBMC) in relapse compared to remission. Lower serum concentrations of CXCL8 and CXCL10 in RRMS patients and decreased peripheral production of CXCL8 in relapse may indicate compensatory anti-inflammatory counter-regulation in MS
Diagnosis of Two Unrelated Syndromes of Prader-Willi and Calpainopathy: Insight from Trio Whole Genome Analysis and Isodisomy Mapping
No full textPurpose: An investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM#176270) using joint whole genome sequencing (WGS).
Methods: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected.
Results: Results showed maternal isodisomy uniparental disomy (UPD) in chromosome 15, expanding from 15q11.2 to 15q22.2, including PWS regions at 15q11.2–15q13. Maternal heterodisomy was detected from 15q22.2 to 15q26.3. A pathogenic variant, NM_000070.3(CAPN3):c.550del (p.Thr184fs), was identified at 15q15.1 in a heterozygous state in the mother that was homozygous in the proband due to maternal isodisomy.
Conclusion: This is the first study of the concurrent molecular etiology of PWS and calpainopathy (OMIM#253600) in the same patient. This report highlights the utility of joint analysis and the need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotypes
Genetic and Epigenetic Biomarkers Linking Alzheimer’s Disease and Age-Related Macular Degeneration
No full textAlzheimer’s disease (AD) represents a prominent neurodegenerative disorder (NDD), accounting for the majority of dementia cases worldwide. In addition to memory deficits, individuals with AD also experience alterations in the visual system. As the retina is an extension of the central nervous system (CNS), the loss in retinal ganglion cells manifests clinically as decreased visual acuity, narrowed visual field, and reduced contrast sensitivity. Among the extensively studied retinal disorders, age-related macular degeneration (AMD) shares numerous aging processes and risk factors with NDDs such as cognitive impairment that occurs in AD. Histopathological investigations have revealed similarities in pathological deposits found in the retina and brain of patients with AD and AMD. Cellular aging processes demonstrate similar associations with organelles and signaling pathways in retinal and brain tissues. Despite these similarities, there are distinct genetic backgrounds underlying these diseases. This review comprehensively explores the genetic similarities and differences between AMD and AD. The purpose of this review is to discuss the parallels and differences between AMD and AD in terms of pathophysiology, genetics, and epigenetics
Evaluating academic detailing as an antibiotic stewardship intervention in primary healthcare settings in Croatia
No full textBackground: Acute respiratory tract infections are common in primary healthcare care settings and frequently result in antibiotic prescriptions, despite being primarily viral. There is scarcity of research examining impact of academic detailing (AD) intervention on prescribing practices for these infections in resource-constrained healthcare settings like southeastern Europe. Therefore aim of this study was to evaluate impact of AD intervention as an antimicrobial stewardship measure on antibiotic prescribing for acute respiratory tract infections in primary setting in Croatia which is located in southeastern Europe. Secondary goal included examining incidence of Clostridioides difficile infections (CDI) which are often associated with antibiotic consumption.
Methods: AD intervention was implemented from 1st to 30th April 2020 and led by hospital healthcare professionals (infectious disease physician, clinical microbiology physician and clinical pharmacist). They focused on enhancing prescribing behaviors of primary care physicians (PCPs) by presenting local data, supplemented by examples from everyday practice, research and guidelines highlighting negative consequences of imprudent antibiotic use. This feasibility quasi-experimental study had two control groups in two counties. Impact of AD intervention was assessed by analyzing antibiotic prescription patterns using log-linear model, adjusting for seasonality. Study focused on prescribed daily defined doses (DDD) per day among PCPs pre-intervention (from 01st January 2018 to 31st March 2020) and post-intervention (from 1st May 2020 to 31st December 2022).
Results: Data was collected from sixteen out of fifty-seven eligible PCPs with mean 29 years (SD 11.38) in practice. Statistically significant difference results (p < 0.05) favored AD intervention, leading to 30% decline in antibiotic prescribing in adjusted DDD per day for acute pharyngitis (21.14 post-intervention/30.27 pre-intervention), 33% decline for acute tonsilitis (24.91/37.38), 23% decline for acute upper respiratory infection (21.26/27.62) and 36% decline for acute bronchitis (8.13/12.77). Although there was 14% decline for acute sinusitis post-intervention, it did not reach statistical significance (30.96/35.93) (p = 0.617). Incidence of CDI cases decreased in investigated county while in control county stayed the same. Inter-county difference in these changes was not statistically significant (ratio = 0.749, 95% CI, 0.460-1.220; p = 0.246).
Conclusions: This feasibility study showed reductions in antibiotic prescribing for acute respiratory tract infections, emphasizing the efficacy of targeted, educator-led programs. Tailored healthcare strategies are vital, especially in Croatia and southeastern Europe, for promoting sustainable practices and addressing antimicrobial resistance challenges