Veterinary medicine - Repository of PHD, master's thesis
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Smokers' Characteristics Associated with Successful Smoking Cessation Undergoing Pharmacotherapy in Slovenia
No full textIntroduction: Tobacco use is a major global health problem, contributing to premature death and disability. In Slovenia, the prevalence of smoking is higher than the EU average, emphasizing the need for effective tobacco control measures. The aim of this study was to identify the characteristics of patients most likely to benefit from pharmacotherapy for smoking cessation.
Methods: We performed cross-sectional analysis of factors associated with successful smoking cessation using pharmacotherapy for Slovenian smokers. A total of 176 (24.6%) smokers with an average age of 50 years agreed to receive pharmacotherapy for their smoking cessation attempt and were enrolled in the study. Participants were followed up at 4-week intervals during treatment and for 24 weeks after completion of pharmacotherapy.
Results: Attempts to quit smoking with prescription medications were successful in 24.4% of those willing to try. Female smokers, older persons, those with more children, with a lower self-perception of health, a higher number of cigarettes per day and a higher nicotine dependence were more likely to attempt to quit smoking. However, the strongest predictors of smoking cessation success were lower nicotine dependence, which was tested using the Fagerström test for nicotine dependence, and higher adherence to pharmacotherapy.
Conclusion: Nicotine dependence and adherence to pharmacotherapy are the strongest predictors of a successful smoking cessation attempt. Identification of potential responders, prescription of pharmacotherapy and follow-up are applicable in the primary healthcare setting
Effective induction immunotherapy minimizes surgical invasiveness for locally advanced lung cancer
No full textBackground: Immunotherapy has been recommended for neoadjuvant therapy in patients with locally advanced non-small cell lung cancer (NSCLC). However, its effect on surgical resection has not yet been examined. This study aimed to examine the effect of induction immunotherapy on surgical resection in terms of the surgical approach, resection extent, and perioperative recovery.
Methods: We performed a real-world study comprising consecutive patients with clinical stage IB-IIIB NSCLC who received surgical resection after induction immunotherapy from January 2019 to September 2021. The perioperative outcomes were compared in terms of the surgical approach and resection extent.
Results: Among 68 patients, 37 (54.4%) achieved a clinical objective response. Standard resection was performed in 37 patients (54.4%), while extended resection was necessary in the other 31 patients (45.6%). Minimally invasive surgery (MIS) was attempted in 37 cases (54.4%), with only 1 (2.7%) conversion. MIS was significantly more commonly accomplished in patients with a clinical objective response than those without (67.6% vs. 35.5%, P=0.008). Patients with a clinical objective response were more likely to have their tumors removed via MIS and/or standard resection (75.7% vs. 51.6%, P=0.04), while those without a clinical objective response more often required extended resection using an open approach. Patients receiving standard resection or MIS had significantly better perioperative outcomes than those who underwent extended resection or thoracotomy (all P<0.05).
Conclusions: The results of this large single-center retrospective cohort indicate that in terms of a better clinical response, effective induction immunotherapy could help reduce the resection extent and/or provide more opportunities to perform MIS, resulting in better recovery
Ceftriaxone Inhibits Conditioned Fear and Compulsive-like Repetitive Marble Digging without Central Nervous System Side Effects Typical of Diazepam—A Study on DBA2/J Mice and a High-5HT Subline of Wistar–Zagreb 5HT Rats
No full textBackground: Ceftriaxone upregulates GLT1 glutamate transporter in the brain and may have anti-CFC and anti-OCD effects. Methods: Twenty WZ-5HT rats were used to investigate the effects of ceftriaxone on obsessive–compulsive (OCD)-like behaviour in the marble-burying (MB) test, freezing behaviour in contextual fear conditioning (CFC) and expression of GLT1 protein in the hippocampus or amygdala using immunoblots. Fifteen DBA/2J mice were used in the MB test. We also compared diazepam with ceftriaxone in open-field, beam-walking, and wire-hanging tests on 47 DBA/2J mice. Ceftriaxone (200 mg/kg) and saline were applied intraperitoneally, once daily for 7 (rats) or 5 (mice) consecutive days. A single dose of diazepam (1.5–3.0 mg/kg) or saline was injected 30 min before the behavioural tests. Results: Ceftriaxone significantly diminished OCD-like behaviour (↓ number of marbles buried) and freezing behaviour in CFC context session (↑ latencies, ↓ total duration, ↓ duration over four 2 min periods of the session) but increased GLT1 protein expression in the amygdala and hippocampus of rats. Diazepam induced sedation, ataxia and myorelaxation in mice. Ceftriaxone did not have these side effects. Conclusions: The results of this study confirm the anti-CFC and anti-OCD effects of ceftriaxone, which did not produce the unwanted effects typical of diazepam
Association of Functional Polymorphisms in MSH3 and IL-6 Pathway Genes with Different Types of Microsatellite Instability in Sporadic Colorectal Cancer
No full textMicrosatellite instability (MSI) has been recognized as an important factor in colorectal cancer (CRC). It arises due to deficient mismatch repair (MMR), mostly attributed to MLH1 and MSH2 loss of function leading to a global MMR defect affecting mononucleotide and longer microsatellite loci. Recently, microsatellite instability at tetranucleotide loci, independent of the global MMR defect context, has been suggested to represent a distinct entity with possibly different consequences for tumorigenesis. It arises as a result of an isolated MSH3 loss of function due to its translocation from the nucleus to the cytoplasm under the influence of interleukin-6 (IL-6). In this study the influence of MSH3 and IL-6 signaling pathway polymorphisms (MSH3 exon 1, MSH3+3133A/G, IL-6-174G/C, IL-6R+48892A/C, and gp130+148G/C) on the occurrence of different types of microsatellite instability in sporadic CRC was examined by PCR–RFLP and real-time PCR SNP analyses. A significant difference in distribution of gp130+148G/C genotypes (p = 0.037) and alleles (p = 0.031) was observed in CRC patients with the C allele being less common in tumors with di- and tetranucleotide instability (isolated MSH3 loss of function) compared to tumors without microsatellite instability. A functional polymorphism in gp130 might modulate the IL-6 signaling pathway, directing it toward the occurrence of microsatellite instability corresponding to the IL-6-mediated MSH3 loss of function
Intravesical Gemcitabine and Docetaxel Therapy for BCG-Naïve Patients: A Promising Approach to Non-Muscle Invasive Bladder Cancer
No full textBacillus Calmette-Guérin (BCG) therapy for patients with non-muscle invasive bladder cancer (NMIBC) faces limitations in efficacy and significant side effects, aggravated by a recent global shortage. In this prospective clinical study, we report the outcomes of sequential intravesical administration of gemcitabine and docetaxel (Gem/Doce) as a first-line treatment for BCG-naïve patients with high-risk NMIBC (HR NMIBC). From October 2019 until April 2022, we enrolled 52 patients and followed the treatment protocol set forth by the University of Iowa. Follow-up assessments were conducted every 3 months. In this cohort, 25 (48.1%) patients were diagnosed with high-grade T1 (T1HG) bladder cancer, 10 (19.2%) patients had carcinoma in situ (CIS), and 17 (32.7%) patients had a combination of T1HG+CIS. The median time to first recurrence in the T1HG, CIS, and T1HG+CIS groups was 11, 10.5, and 8.8 months, respectively. The recurrence-free survival was 98.1%, 94.2%, and 80.8% at 6, 9, and 12 months, respectively. The rate of progression-free survival was 100%, 98.1%, and 92.3% at 6, 9, and 12 months, respectively. We demonstrated the safety and efficacy of Gem/Doce therapy in BCG-naïve patients with HR NMIBC during a one-year follow-up. Further research with extended follow-ups, as well as direct comparisons of Gem/Doce with other anticancer agents, is essential
Retrospective analysis of the incidence and outcome of late acute and chronic graft-versus-host disease—an analysis from transplant centers across Europe
No full textIntroduction: Chronic graft-versus-host disease (cGvHD) is a serious late complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Methods: This multicenter analysis determined the cumulative incidence (CI) of cGvHD and late acute GvHD (laGvHD) and its impact on transplantation-related mortality (TRM), relapse (R), and overall survival (OS) in 317 patients [296 adults, 21 pediatrics (<12 years of age)] who underwent their first allo-HSCT in 2017.
Results: The CI of laGvHD was 10.5% in adults and 4.8% in pediatrics, and the CI of cGvHD was 43.0% in all adult transplant patients and 50.2% in the adult at-risk cohort at the study end. The onset of cGvHD was de novo in 42.0% of patients, quiescent in 52.1%, and progressive in 5.9%. In adults, prophylactic use of antithymocyte globulin or posttransplant cyclophosphamide was associated with a significantly lower incidence of cGvHD (28.7%) vs. standard prophylaxis with calcineurin inhibitors (30.6%) and methotrexate/mycophenolate mofetil (58.4%) (all p < 0.01). TRM was significantly higher in patients with aGvHD (31.8%) vs. cGvHD (12.6%) and no GvHD (6.3%) (all p = 0.0001). OS in the adult at-risk cohort was significantly higher in patients with cGvHD (78.9%) vs. without (66.2%; p = 0.0022; HR 0.48) due to a significantly lower relapse rate (cGvHD: 14.5%; without cGvHD: 27.2%; p = 0.00016, HR 0.41). OS was also significantly higher in patients with mild (80.0%) and moderate (79.2%) cGvHD vs. without cGvHD (66.2%), excluding severe cGvHD (72.7%) (all p = 0.0214).
Discussion: The negative impact of severe cGvHD on OS suggests a focus on prevention of severe forms is warranted to improve survival and quality of life
Improving blood pressure and dyslipidemia control by increasing health literacy in Croatia-missions 70/26 & Do you know what is your number
No full textPurpose: In 2022 hypertensive disease was the second cause of death in Croatia. The crude prevalence of hypertension is increasing and still majority of hypertensive patients did not reach blood pressure and cholesterol goals Low awareness, and small number of treated and controlled patients point on poor adherence and even worse clinical inertia.
Materials and methods: Croatian Hypertension League (CHL) has started the permanent public health action Hunting the Silent Killer aiming to increase health literacy. In 2023 we decided to intensify program with two missions - '70/26', and 'Do you know what is your number?' aiming to achieve target values in 70% and in 50% of patients treated for hypertension and dyslipidaemia, respectively, by 2026. For the health care workers, the program will primarily involve digital education, and 'School of Communication in Hypertension'. In the second arm of the program, we will advise patients and general population to visit our educational website with important and useful information on how to improve bad lifestyle, how to proper measure blood pressure, why is it important to sustain in taking drugs etc. In 2026, the CHL will organise field research to assess the success of programs using the same methodology as we used in previous EH-UH studies.
Conclusion: We will monitor and analyse trends in the management and control of patients treated for hypertension and dyslipidaemia. This will enable us to make an evidence-based conclusion how successful we were in increasing health literacy
Exploring the accessibility of primary health care data in Europe's COVID-19 response: developing key indicators for managing future pandemics (Eurodata study)
No full textBackground: Primary Health Care (PHC) plays a crucial role in managing the COVID-19 pandemic, with only 8% of cases requiring hospitalization. However, PHC COVID-19 data often goes unnoticed on European government dashboards and in media discussions. This project aims to examine official information on PHC patient care during the COVID-19 pandemic in Europe, with specific objectives: (1) Describe PHC's clinical pathways for acute COVID-19 cases, including long-term care facilities, (2) Describe PHC COVID-19 pandemic indicators, (3) Develop COVID-19 PHC activity indicators, (4) Explain PHC's role in vaccination strategies, and (5) Create a PHC contingency plan for future pandemics.
Methods: A mixed-method study will employ two online questionnaires to gather retrospective PHC data on COVID-19 management and PHC involvement in vaccination strategies. Validation will occur through focus group discussions with medical and public health (PH) experts. A two-wave Delphi survey will establish a European PHC indicators dashboard for future pandemics. Additionally, a coordinated health system action plan involving PHC, secondary care, and PH will be devised to address future pandemic scenarios.
Analysis: Quantitative data will be analysed using STATA v16.0 for descriptive and multivariate analyses. Qualitative data will be collected through peer-reviewed questionnaires and content analysis of focus group discussions. A Delphi survey and multiple focus groups will be employed to achieve consensus on PHC indicators and a common European health system response plan for future pandemics. The Eurodata research group involving researchers from 28 European countries support the development.
Discussion: While PHC manages most COVID-19 acute cases, data remains limited in many European countries. This study collects data from numerous countries, offering a comprehensive perspective on PHC's role during the pandemic in Europe. It pioneers the development of a PHC dashboard and health system plan for pandemics in Europe. These results may prove invaluable in future pandemics. However, data may have biases due to key informants' involvement and may not fully represent all European GP practices. PHC has a significant role in the management of the COVID-19 pandemic, as most of the cases are mild or moderate and only 8% needed hospitalization. However, PHC COVID-19 activity data is invisible on governments' daily dashboards in Europe, often overlooked in media and public debates
Methylation of RB1, H19 genes and LINE 1 repetitive sequence during fetal development of testis in man and in rat
No full textNeki od uzroka muške neplodnost mogu imati ishodište u epigenetičkim poremećajima tijekom prenatalnog života. Cilj disertacije bio je istražiti DNA metilaciju LINE-1 transpozonskih ponavljajućih sljedova i diferencijalno metilirane regije (DMR) utisnutog gena H19 u tkivu fetalnog sjemenika čovjeka i štakora te RB1 tumorsupresorskog gena u čovjeka usporedno sa staničnom proliferacijom i izražajem tumor supresora RB1 te njegovih fosforiliranih oblika. DNA metilacija u fetalnom štakorskom sjemeniku značajno raste za LINE-1 od 16.5 do 21.5 dpc, a za H19 do 17.5 dpc. Analiza ljudskih uzoraka pokazuje visoku razinu metilacije LINE-1 tijekom trudnoće te značajno sniženje u pubertetu, a za H19 rast do kraja trudnoće, dok je RB1 tijekom trudnoće hipometiliran (ispod 5%). Izražaj biljega proliferacije Ki-67 u štakorskom sjemeniku značajno se smanjuje od 16.5 do 19.5 dpc kao i izražaj fosforiliranih RB1 proteina u odnosu na ukupan broj stanica i promjer kanalića, a zatim se povisuje (19.5 - 20.5 dpc). U ljudskim sjemenicima izražaj Ki-67 i fosforiliranih oblika RB1 u odnosu na ukupan broj stanica i promjer kanalića pada od prvog prema drugom tromjesječju, a od drugog prema trećem raste ukupni RB1 i dio fosforiliranih formi. Rezultati ovog rada značajni su kao baza za daljnje istraživanje uzroka neplodnosti ili tumora sjemenika koji mogu biti uzrokovani promjenom metilacije gena koji djeluju na stabilnost genoma, genomsko utiskivanje i regulaciju staničnog ciklusa.Some of the causes of male infertility may have their origin in epigenetic disorders during prenatal life. The aim of the study was to investigate DNA methylation of LINE-1 transposon repetitive sequences and the imprinted differentially methylated region (DMR) of H19 gene in human and rat fetal testis and the RB1 tumor supressor gene in humans in parallel with the expression of RB1 protein and its phosphorylated forms. DNA methylation in the fetal rat testis increases significantly for LINE-1 from 16.5 to 21.5 dpc, and for H19 to 17.5 dpc. Analysis of human samples showed a high level of LINE-1 methylation during pregnancy with a significant decrease in puberty, and for H19 an increase until the end of pregnancy, while RB1 was hypomethylated during pregnancy (below 5%). The expression of Ki-67 proliferation marker in the rat testis is significantly reduced from 16.5 to 19.5 dpc as well as the expression of phosphorylated RB1 proteins from 16.5 and 19.5 relative to total cell number and tubular diameter, and is increased from 19.5 to 20.5. In human testes, the expression of Ki-67 and phosphorylated RB1 in relation to the total number of cells and the diameter of the tubules decreases from the first to the second trimester, and from the second to the third the total RB1 and a part of the phosphorylated forms increase. The results of this work are important as a basis for further research into the causes of infertility or testicular tumors that may be caused by altered methylation of genes that affect genome stability, genomic imprinting, and cell cycle regulation
The effects of diabetes mellitus on edema development and microglial response in a mouse model of cerebral and retinal ischemia via modulation of bradykinin receptors expression
No full textŠećerna bolest, kao učestali komorbiditet u podlozi ishemije mozga i mrežnice, mijenja izražaj bradikininskih receptora uključenih u postishemijski upalni odgovor. Cilj ovog istraživanja bio je odrediti kako šećerna bolest utječe na ulogu signalnog puta bradikinina u razvoju edema te aktivaciji i migraciju mikroglije u mišjem modelu ishemijske ozljede mozga i mrežnice. Miševima s dijabetesom tipa 1, dijabetičnim miševima s onemogućenim genom za bradikininski receptor tipa 2 te njihovim nedijabetičnim kontrolama inducirana je ishemija simultanom okluzijom srednje moždane i pterigopalatine arterije. Rezultati pokazuju uključenost bradikininskog receptora tipa 2 u metabolizam glukoze i razvoj očne hipertenzije u dijabetičnih miševa. Pokazuju i da šećerna bolest različito modulira izražaj bradikinskih receptora u mozgu i mrežnici, pojačava razvoj moždanog i mrežničnog edema, postishemijsku aktivaciju stanica mikroglije i gubitak istih, dok nedostatak bradikininskog receptora tipa 2 u šećernoj bolesti smanjuje odgovor mikroglije, progresiju neurološkog deficita i edem mrežnice. U odsutnosti šećerne bolesti, nedostatak bradikininskog receptora tipa 2 smanjuje vaskularnu propusnost mozga i pospješuje preživljenje mikroglije, ali istovremeno pojačava postishemijski edem mrežnice i aktivaciju mikroglije. Ovim radom je pokazano da šećerna bolest mijenja ulogu bradikinskog receptora tipa 2 u postishemijskom upalnom odgovoru mozga i mrežnice te ukazuje na važnost uključenja komorbiditeta u pretklinička istraživanja ishemijskog moždanog udara.Diabetes mellitus, underlying brain and retinal ischemia, changes the expression of bradykinin receptors in the postischemic inflammatory response. The aim of this research was to determine how diabetes modulates the role of bradykinin signalling pathway in edema development and microglial response in a mouse model of cerebral and retinal ischemia. Ischemia was induced by simultaneous occlusion of the middle cerebral and pterygopalatine arteries in type 1 diabetic mice, bradykinin receptor type 2 knock-out diabetic mice, and their non-diabetic controls. The results show the involvement of bradykinin receptor type 2 in glucose metabolism and ocular hypertension development in diabetic mice. Diabetes changes the expression of bradykinin receptors in the brain and retina differently, enhances brain and retinal edema development, postischemic activation and loss of microglia, while bradykinin receptor type 2 deficiency in diabetes reduces the microglial response, retinal edema, and progression of neurological deficit. In normoglycemia, bradykinin receptor deficiency reduces cerebral vascular permeability and promotes microglial survival, but at the same time enhances retinal edema formation and microglial activation. This work has shown that diabetes changes the role of bradykinin receptor type 2 in postischemic inflammatory response and underlines the importance of the inclusion of comorbidities in preclinical stroke research