Veterinary medicine - Repository of PHD, master's thesis
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Transplantation of neural stem cells improves recovery of stroke-affected mice and induces cell-specific changes in GSDMD and MLKL expression
No full textIntroduction: Stroke, the second leading cause of death and disability in Europe, is primarily caused by interrupted blood supply, leading to ischemia-reperfusion (IR) injury and subsequent neuronal death. Current treatment options are limited, highlighting the need for novel therapies. Neural stem cells (NSCs) have shown promise in treating various neurological disorders, including stroke. However, the underlying mechanisms of NSC-mediated recovery remain unclear.
Methods: Eighty C57Bl/6-Tyrc-Brd mice underwent ischemic stroke induction and were divided into four groups: sham, stroke-affected, stroke-affected with basal cell medium injection, and stroke-affected with NSCs transplantation. NSCs, isolated from mouse embryos, were stereotaxically transplanted into the stroke-affected brains. Magnetic resonance imaging (MRI) and neurological scoring were used to assess recovery. Immunohistochemical analysis and gene expression assays were performed to evaluate pyroptosis and necroptosis markers.
Results: NSC transplantation significantly improved neurological recovery compared to control groups. In addition, although not statistically significant, NSCs reduced stroke volume. Immunohistochemical analysis revealed upregulation of Gasdermin D (GSDMD) expression post-stroke, predominantly in microglia and astrocytes. However, NSC transplantation led to a reduction in GSDMD signal intensity in astrocytes, suggesting an effect of NSCs on GSDMD activity. Furthermore, NSCs downregulated Mixed Lineage Kinase Domain-Like Protein (Mlkl) expression, indicating a reduction in necroptosis. Immunohistochemistry demonstrated decreased phosphorylated MLKL (pMLKL) signal intensity in neurons while stayed the same in astrocytes following NSC transplantation, along with increased distribution in microglia.
Discussion: NSC transplantation holds therapeutic potential in stroke recovery by targeting pyroptosis and necroptosis pathways. These findings shed light on the mechanisms underlying NSC-mediated neuroprotection and support their further exploration as a promising therapy for stroke patients
Virulence and resistance factors of Nakaseomyces glabratus (formerly known as Candida glabrata) in Europe: A systematic review
No full textBackground: Nakaseomyces glabratus (N. glabratus) formerly known as Candida glabrata (C. glabrata), is an endogenous opportunistic pathogen, which is generally located in the gastrointestinal tract but can spread in immunocompromised patients. N. glabratus is the second most common pathogen that causes candidemia in several countries. N. glabratus virulence factors may increase antifungal resistance and reduce the number of available treatment options. High resistance to azoles and increasing resistance to echinocandins have been previously reported in N. glabratus.
Objective: To establish the distribution of N. glabratus isolates in Europe and its drug susceptibility/resistance in each country over the last 7 years.
Methods: The search was performed across three databases: PubMed, Scopus and Scielo, using the MeSH terms: "Candida glabrata", "Nakaseomyces glabratus", "Europe", "resistance" and "Epidemiology" exclusively in English. All available information from January 2002 to December 2022 was included, excluding reviews, meta-analyses and book chapters.
Results: Fifty-seven articles with information on antifungal susceptibility in Europe were retrieved and analysed with a total of 15,400 reported C. glabrata isolates. Remarkably, nations that presented the maximum number of cases during the study period included the United Kingdom (n = 7241, 47.02%), France (n = 3190, 20.71%), Spain (n = 900, 5.84%), Hungary (n = 745, 4.84%) and Italy (n = 486, 3.16%). C. glabrata isolates presented resistance to azoles [voriconazole (n = 2225, 14.45%), fluconazole (n = 1612, 10.47%), itraconazole (n = 337, 2.19%) and clotrimazole (n = 89, 0.58%)], increased resistance to echinocandins, especially to anidulafungin (n = 138, 0.89%), and high sensitivity to amphotericin B.
Conclusions: The number of candidemia cases associated with triazole-resistant N. glabratus isolates have been increasing in Europe. Therefore, echinocandins and amphotericin B can be considered optional empirical treatments; however, antifungal susceptibility testing is required to determine the best therapeutic options
No impact of steatotic liver disease on clinical outcomes in patients with essential thrombocythemia and polycythemia vera: A pilot study
No full textThe presence of steatotic liver disease (SLD) is associated with an increased cardiovascular risk in the general population. Chronic myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET) and polycythemia vera (PV), are characterized by clonal myeloproliferation, chronic inflammatory state, and increased cardiovascular morbidity and mortality. The aim of this single-center study was to analyze clinical associations and the potential prognostic impact of SLD in ET and PV patients. We retrospectively included 108 patients (64 ET and 44 PV); median age was 70.5 years (range 21-92), 68 (63 %) were females, and the median follow-up time was 69 months. Baseline SLD presence was defined ultrasonographically and was detected in 25 (23.1 %) patients. There were no associations of SLD with any of the clinical and laboratory patient characterictics. Also, baseline ultrasonographic presence of SLD did not have an impact on future thrombotic, bleeding and disease transformation risk, nor patient survival. None of the patients experienced signs of liver failure during the follow-up. In conclusion, the presence of SLD in ET and PV patients does not seem to have major clinical implications. Therefore, patients may be advised about the generally harmless nature of SLD when occurring in the MPN context
The Use of COVID-19 Mobile Apps in Connecting Patients with Primary Healthcare in 30 Countries: Eurodata Study
No full textBackground: The COVID-19 pandemic has necessitated changes in European healthcare systems, with a significant proportion of COVID-19 cases being managed on an outpatient basis in primary healthcare (PHC). To alleviate the burden on healthcare facilities, many European countries developed contact-tracing apps and symptom checkers to identify potential cases. As the pandemic evolved, the European Union introduced the Digital COVID-19 Certificate for travel, which relies on vaccination, recent recovery, or negative test results. However, the integration between these apps and PHC has not been thoroughly explored in Europe.
Objective: To describe if governmental COVID-19 apps allowed COVID-19 patients to connect with PHC through their apps in Europe and to examine how the Digital COVID-19 Certificate was obtained.
Methodology: Design and setting: Retrospective descriptive study in PHC in 30 European countries. An ad hoc, semi-structured questionnaire was developed to collect country-specific data on primary healthcare activity during the COVID-19 pandemic and the use of information technology tools to support medical care from 15 March 2020 to 31 August 2021. Key informants belong to the WONCA Europe network (World Organization of Family Doctors). The data were collected from relevant and reliable official sources, such as governmental websites and guidelines. Main outcome measures: Patient’s first contact with health system, governmental COVID-19 app (name and function), Digital COVID-19 Certification, COVID-19 app connection with PHC.
Results: Primary care was the first point of care for suspected COVID-19 patients in 28 countries, and 24 countries developed apps to complement classical medical care. The most frequently developed app was for tracing COVID-19 cases (24 countries), followed by the Digital COVID-19 Certificate app (17 countries). Bulgaria, Italy, Serbia, North Macedonia, and Romania had interoperability between PHC and COVID-19 apps, and Poland and Romania’s apps considered social needs. Conclusions: COVID-19 apps were widely created during the first pandemic year. Contact tracing was the most frequent function found in the registered apps. Connection with PHC was scarcely developed. In future pandemics, connections between health system levels should be guaranteed to develop and implement effective strategies for managing diseases
Utilizing Deep Learning for Diagnosing Radicular Cysts
No full textObjectives: The purpose of this study was to develop a deep learning algorithm capable of diagnosing radicular cysts in the lower jaw on panoramic radiographs.
Materials and methods: In this study, we conducted a comprehensive analysis of 138 radicular cysts and 100 normal panoramic radiographs collected from 2013 to 2023 at Clinical Hospital Dubrava. The images were annotated by a team comprising a radiologist and a maxillofacial surgeon, utilizing the GNU Image Manipulation Program. Furthermore, the dataset was enriched through the application of various augmentation techniques to improve its robustness. The evaluation of the algorithm's performance and a deep dive into its mechanics were achieved using performance metrics and EigenCAM maps.
Results: In the task of diagnosing radicular cysts, the initial algorithm performance-without the use of augmentation techniques-yielded the following scores: precision at 85.8%, recall at 66.7%, mean average precision (mAP)@50 threshold at 70.9%, and mAP@50-95 thresholds at 60.2%. The introduction of image augmentation techniques led to the precision of 74%, recall of 77.8%, mAP@50 threshold to 89.6%, and mAP@50-95 thresholds of 71.7, respectively. Also, the precision and recall were transformed into F1 scores to provide a balanced evaluation of model performance. The weighted function of these metrics determined the overall efficacy of our models. In our evaluation, non-augmented data achieved F1 scores of 0.750, while augmented data achieved slightly higher scores of 0.758.
Conclusion: Our study underscores the pivotal role that deep learning is poised to play in the future of oral and maxillofacial radiology. Furthermore, the algorithm developed through this research demonstrates a capability to diagnose radicular cysts accurately, heralding a significant advancement in the field
Salivary Cortisol Concentration Is an Objective Measure of the Physiological Response to Loud Music
No full textPurpose: This study examines the potential associations between salivary cortisol concentrations and subjective stress test scores in healthy individuals subjected to sound-related, psychological, and physical stressors.
Methods: This study employed a single-center observational cross-sectional design, with a sample size of 36 subjects recruited from a tertiary referral audiology center. Between 2023 and 2024, the study recruited subjects with normal hearing, baseline salivary cortisol levels, and subjective stress levels. The participants were requested to complete an STAI-Y1 questionnaire and provide salivary cortisol samples before and following exposure to sound-related, psychological, and physical stress tests.
Results: Exposure to psychological and physical stressors significantly increased STAI-Y1 scores (Friedman’s test, χ2 = 57.118, df = 2, p = 0.377). This increase was greater than that observed in response to loud, favorite music (Friedman’s test, χ2 = 57.118, df = 2, p 0.05).
Conclusions: Exposure to loud favorite music increases salivary cortisol concentrations, as does acute physical and psychological stress. Interestingly, unlike psychological and physical stress, loud music was not objectively perceived as stress, which may mask the physiological signs of stress, potentially increasing the risk of both acute and chronic stress-related health outcomes
PCSK9 inhibition: from effectiveness to cost-effectiveness
No full textDyslipidaemia is a complex disorder characterised by abnormal lipid levels in the blood, including cholesterol and triglycerides, and plays an important role in the development of atherosclerotic cardiovascular disease. Most risk factors for cardiovascular disease are modifiable, and dyslipidaemia is a key factor among them. It can result from a combination of genetic and environmental factors. A distinction is made between primary dyslipidaemia, which is mainly caused by inherited genetic changes, and secondary dyslipidaemia, which is due to underlying diseases or certain medications. The treatment of dyslipidaemia has evolved over the years. In the past, statins were the first choice, but newer drugs, such as proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, have gained prominence due to their effectiveness in lowering lipids. Although recent guidelines recommend PCSK9 inhibitors for high-risk patients and patients who cannot tolerate statins, their widespread use is limited because of cost. Several meta-analyses have confirmed the efficacy and safety of PCSK9 inhibitors and have shown a significant reduction in low-density lipoprotein (LDL) cholesterol levels. However, the long-term side effects and interactions with other risk factors for cardiovascular disease remain uncertain. In addition, cost-effectiveness analyses have shown mixed results, with some countries considering PCSK9 inhibitors to be cost-effective for certain patient groups, while others consider them less economical. Meanwhile, initial data from patients using PCSK9 inhibitors support the results of the clinical trials. To summarise, PCSK9 inhibitors represent a revolutionary solution for lowering LDL cholesterol, but their cost-effectiveness remains controversial. Despite the controversy, they offer clear benefits for high-risk patients and should therefore be considered in the treatment of dyslipidaemia
Brown tumors in primary hyperparathyroidism initially interpreted as bone metastases and multiple gigantocelular tumors: case report
No full textBrown tumors or osteitis fibrosa cystica are a rare bone metabolism disorder that may mimic cancer metastasis. It represents a late manifestation of prolonged and mostly unrecognized hyperparathyroidism. In this case report we present a 44-year-old female patient with multiple lesions detected on bone scintigraphy and 18F- FDG-PET/CT, initially interpreted as a bone metastatic disease, rather than multiple gigantocellular bone tumors. Additionally, the presented case emphasizes the importance of a multidisciplinary approach in diagnosing brown tumors as part of hyperparathyroidism, and the treatment decision
Professional challenges of nurses in the intensive neurological treatment unit
No full textMedicinske sestre imaju ključnu ulogu u zdravstvenom sustavu zbog specifične skrbi koju pružaju pacijentima. Sestrinska profesija općenito je izazovna i zahtjevna, a posebno se to odnosi na rad u jedinicama intezivnog liječenja, uključujući jedinice intezivnog neurološkog liječenja. Profesionalni izazovi s kojima se medicinske sestre zaposlene u jedinici intenzivnog neurološkog liječenja suočavaju su mnogobrojni, a odnose se na specifična znanja i vještine povezane s monitoringom pacijenata i tehničkom opremom, umorom i smanjenom razinom budnosti, nezadovoljstvom poslom, stresom, bukom, moralnom osjetljivošću, emocionalnom inteligencijom, učinkovitom komunikacijom, organizacijskim aspektima sestrinske skrbi te lošim ergonomskim uvjetima. Većina osoba koja se pridruži sestrinstvu kao profesiji ima fizičku i mentalnu izdržljivost višu od prosjeka i sposobne su pronaći razne načine prilagodbe profesionalnim izazovima. Pacijenti liječeni u jedinici intenzivnog neurološkog liječenja mogu doživjeti negativne ishode nastale kao rezultat nekvalitetno učinjene njege kao što su pojava intrahospitalnih infekcija, duže vrijeme hospitalizacije te povećanje stope mortaliteta. Kako bi se smanjili i/ili spriječili negativni ishodi liječenja, potrebno je podići svijest javnosti o prisutnim problemima, provesti više istraživanja te uložiti više napora u pravilnu raspodjelu vještina sestrinstva na temelju dostupnih dokaza te zdravstvenih resursa.Nurses play a key role in the healthcare system because of the specific care they provide to patients. The nursing profession is generally challenging and demanding, and this especially applies to work in intensive care units, including neurological intensive care units. The professional challenges faced by nurses employed in the intensive neurological treatment unit are numerous, and they relate to specific knowledge and skills related to patient monitoring and technical equipment, fatigue and reduced level of alertness, job dissatisfaction, stress, noise, moral sensitivity, emotional intelligence, effective communication, organizational aspects of nursing care and poor ergonomic conditions. Most people who join nursing as a profession have above average physical and mental endurance and are able to find a variety of ways to adapt to professional challenges. Until now, it is known that patients treated in the intensive neurological treatment unit can experience negative outcomes as a result of low-quality care, such as the occurrence of intrahospital infections, longer periods of hospitalization, and an increase in the mortality rate. In order to reduce and/or prevent such negative treatment outcomes, it is necessary to raise public awareness of the present problems, conduct more research, and put more effort into the proper distribution of nursing skills based on available evidence and health resources