Veterinary medicine - Repository of PHD, master's thesis

Veterinary medicine - Repository of PHD, master's thesis
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    The effect of inflammation on apoptotic cell death after ischemic lesion of the mouse brain

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    Postishemijska upala značajan je faktor u razvoju ozljede nakon moždanog udara, a TLR2 receptor jedan je od njezinih glavnih medijatora. Glavni cilj ovog doktorata bio je odrediti utjecaj upale posredovane TLR2 receptorom na apoptozu u ishemijskom okolišu. Utjecaj TLR2 receptora istražen je na modelu ishemijskog oštećenja mišjeg mozga u životinja s normalnim (CAG-luc) i onih s onemogućenim Tlr2 genom (CAG-luc-Tlr2-/-). Oba soja ubikvitarno su izražavala luciferazni transgen. Razmjer apoptoze pratio se bioluminiscencijom zatočenim Z-DEVD-aminoluciferinom koji se cijepa i postaje bioluminiscentno aktivan nakon interakcije s pocijepanom kaspazom-3. Ishemijska ozljeda bila je uzrokovana okluzijom srednje moždane arterije, a njena progresija praćen je magnetskom rezonancom. Stanična smrt je potvrđena metodama imunofluorescencije pocijepanom kaspazom-3, protočne citometrije aneksinom-V i TUNEL esejom. Funkcionalno oštećenje izmjereno je testom neurološkog deficita. Zatočeni Z-DEVD-aminoluciferin validiran je i procijenjen kao adekvatan supstrat za praćenje apoptoze. Longitudinalno in vivo mjerenje apoptoze izazovno je te zahtijeva kvalitetnu validaciju i normalizaciju. Nije bilo ukupne razlike u apoptozi između sojeva, ali u nedostatku TLR2 receptora postojao je izraženiji mehanizam nekroze. U akutnom periodu, CAG-luc- Tlr2-/- miševi bolje su preživljavali od CAG-luc miševa, dok u kroničnom periodu nije bilo razlike u preživljenju. Ipak, magnetna rezonanca je pokazala kako su CAG-luc-Tlr2-/- miševi su u kroničnom periodu izgubili više tkiva ipsilateralne hemisfere od CAG-luc miševa. Stoga, iako smanjena upala u akutnom periodu može biti protektivna, dugoročno narušava oporavak.Postischemic inflammation is a significant contributor to ischemic injury development. The TLR2 receptor is one of its main mediators. The main aim of this thesis was to determine the effect of TLR2-mediated inflammation on apoptotic cell death in the ischemic environment. The effect of TLR2 was investigated on the ischemic injury model in animals with normal Tlr2 (CAG-luc) and those with knock-out Tlr2 gene (CAG-luc-Tlr2-/-). Both strains expressed the firefly luciferase transgene ubiquitously. The scope of apoptosis was determined by the utilization of bioluminescence imaging with caged Z-DEVD-aminoluciferin, which becomes available for the bioluminescence reaction after cleavage with activated caspase-3. Middle cerebral artery occlusion was performed to produce the ischemic injury. Its progression was followed with magnetic resonance imaging. Cell death was further confirmed using immunofluorescence with activated caspase-3, flow cytometry with annexin-V and the TUNEL assay. Functional outcomes were assessed using a neurological deficit test. Caged Z-DEVD-aminoluciferin was validated and assessed as an adequate tool for monitoring apoptosis. Longitudinal in vivo measurement of apoptosis is challenging and requires thorough validation and normalization. No total difference in apoptosis between the used strains was found. However, in the absence of the TLR2 receptor, a more pronounced mechanism of necrosis arose. In the acute period, CAG-luc-Tlr2-/- mice had better survival than CAG-luc mice. In the chronic period, there was no difference in survival between the strains. However, magnetic resonance imaging showed that CAG-luc-Tlr2-/- lost more ipsilateral hemisphere tissue than CAG-luc mice during the chronic period. Therefore, although lower levels of inflammation may be protective in the acute period post-stroke, long-term recovery is impaired

    Zdravstveni inspektorat kao alat za poboljšanje kvalitete zdravstvene zaštite u javnim ustanovama primarne zdravstvene zaštite na Kosovu

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    Kosovo applies a healthcare organization quality model based on an internal mechanism - Quality Coordinators (QC), and the external mechanism - Health Inspectorate of the Ministry of Health. The hypothesis of this research was that the Health Inspectorate is an efficient regulatory tool for quality improvement in public institutions of primary healthcare (PHC) in Kosovo. Purposefully selected 14 PHC organisations were subjected to initial, follow-up, and final inspections to monitor adherence to 32 basic standards of healthcare quality (BSHQ). QC from the same institutions were tested for healthcare quality knowledge. The lowest scores of both provided selection for seven QC who were subjected to training, and focus group discussion on motivation to serve, experiences, factors that impact quality and suggestions for improvement. Results showed that over the years, adherence to 32 BSHQ and QC knowledge improved. QC believed that the Health Inspectorate positively influences healthcare quality. Suggestions for improvement included QC role, Health Inspectorate and healthcare in general. In conclusion, the research hypothesis was confirmed. The Health Inspectorate can use its formal power to foster a culture of healthcare quality in everyday practices by requesting authorities to provide resources as a prerequisite for quality enhancement.Kosovo primjenjuje model kvalitete zdravstvene organizacije koji se temelji na internom mehanizmu - Koordinatorima kvalitete (QC) i vanjskom mehanizmu - Zdravstvenoj inspekciji Ministarstva zdravlja. Hipoteza ovog istraživanja bila je da je zdravstvena inspekcija učinkovit regulatorni alat za poboljšanje kvalitete javnih ustanova primarne zdravstvene zaštite (PZZ) na Kosovu. Svrhovito odabranih 14 organizacija PZZ-a podvrgnuto je početnim, naknadnim i završnim inspekcijama kako bi se pratilo pridržavanje 32 temeljna standarda zdravstvene kvalitete (BSHQ). QC iz istih ustanova testirani su na poznavanju kvalitete zdravstvene zaštite. Najniže ocjene obje dale su odabir za sedam QC-a koji su bili podvrgnuti obuci i diskusiji u fokusnoj grupi o motivaciji za služenje, iskustvima, čimbenicima koji utječu na kvalitetu i prijedlozima za poboljšanje. Rezultati su pokazali da se tijekom godina poštivanje 32 BSHQ i QC znanja poboljšalo. QC smatra da zdravstvena inspekcija pozitivno utječe na kvalitetu zdravstvene zaštite. Prijedlozi za poboljšanje uključivali su ulogu QC-a, zdravstvene inspekcije i zdravstva općenito. Zaključno, hipoteza istraživanja je potvrđena. Zdravstvena inspekcija može koristiti svoje formalne ovlasti za njegovanje kulture kvalitete zdravstvene skrbi u svakodnevnoj praksi tražeći od vlasti da osiguraju resurse kao preduvjet za poboljšanje kvalitete

    Association of plasma levels of chemokines with metabolic complications of type 1 diabetes and obesity in children

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    U djece sa šećernom bolešću tipa 1 i pretilošću, dobi 12 do 18 godina, analizirali smo profil kemokina i kemokinskih receptora u perifernoj krvi s ciljem usporedbe sa zdravim ispitanicima te utvrđivanja povezanosti s kardiometaboličkim čimbenicima rizika. Koncentracija kemokina CCL2 povišena je u djece s loše reguliranim šećernom bolešću, kemokina CXCL11 snižena je u značajno pretilih, dok je kemokina CXCL12 snižena u obje skupine bolesnika. Uočene su brojne značajne korelacije kemokina i kemokinskih receptora s kardiometaboličkim i upalnim parametrima. U šećernoj bolesti se izdvaja pozitivna korelacija monocita CCR2+ s krvnim tlakom, limfocita B CCR2+ i CXCR3+ s trigliceridima, kemokina CCL2 s udjelom HbA1c i kemokina CXCL12 s omjernom albumina i kreatinina u urinu (ACR), uz negativnu povezanost subpopulacija CCR2+ s ACR. U pretilih dominira pozitivna povezanost kemokina CXCL12 s više metaboličkih parametara, negativna povezanost monocita CCR4+ i CXCR3+ s omjerom ACR te monocita s vrijednostima HOMA-IR. U obje bolesti nalazimo negativnu povezanost subpopulacija CXCR4+ s omjerom ACR i limfocita T CXCR3+ s lipidogramom te pozitivnu povezanost limfocita T CCR4+ s krvnim tlakom. Iako različiti rezultati sugeriraju imunoregulaciju specifičnu za pojedinu bolest, između šećerne bolesti i pretilosti postoje i preklapajući obrasci koji povezuju kemokinske signale s metaboličkom i vaskularnom disfunkcijom te predstavljaju moguće zajedničke terapijske ciljeve.We compared peripheral blood chemokine/receptor profiles in children and adolescents (12-18 years) with type 1 diabetes mellitus (T1D) or obesity to healthy controls and analyzed associations of chemokine network with cardiometabolic risk factors. The level of CCL2 was higher in poorly controlled T1D, CXCL11 was lower in severe obesity and CXCL12 was lower in both diseases. Numerous significant associations were found for chemokine/receptor profiles and cardiometabolic/inflammatory parameters. In T1D we can emphasize positive associations of CCR2+ monocytes with blood pressure, CCR2+ and CXCR3+ B lymphocytes with triglycerides, CCL2 levels with HbA1c and CXCL12 levels with urine albumin-to-creatinine ratio (ACR), and inverse association of CCR2+ subsets with ACR. Major findings in obesity are positive associations of CXCL12 with metabolic parameters, inverse association of CCR4+ and CXCR3+ monocytes with ACR, and CXCR4+ monocytes with HOMA-IR. Both diseases share inverse associations of CXCR4+ subsets with ACR and CXCR3+ T lymphocytes with lipid profile, and positive associations of CCR4+ T lymphocytes with blood pressure. Although different results indicate disease-specific immunoregulation, overlapping patterns found in T1D and obesity suggest shared associations of chemokine axes with metabolic and vascular disfunction. Thus, chemokine axes might present potential common therapeutic targets for disease-related morbidity

    Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)

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    Backgrounds/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of 0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions: Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model

    Bacterial sexually transmitted diseases in the first two years of pre-exposure prophylaxis use for HIV in Croatia

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    Uvod. Korištenje antiretrovirusnih lijekova je dio kombinirane prevencije HIV-infekcije. Najčešće se koristi tenofovir dizoproksil fumarat/emtricitabin i generičke formulacije (TDX/FTC). Dosadašnja istraživanja o pojavnosti spolno prenosivih bolesti (SPB) u korisnika predekspozicijske profilakse (PrEP) pokazala su različite rezultate. Cilj. Procjena incidencije bakterijskih SPB tijekom prve dvije godine korištenja PrEP-a u muškaraca koji imaju odnose s muškarcima (MSM) u Hrvatskoj. Procijeniti prevalenciju SPB kod započinjanja PrEP-a te čimbenike povezane s pojavom nove SPB tijekom praćenja. Metode. Radi se o retrospektivnom i dijelom prospektivnom opservacijskom kohortnom istraživanju s početkom u rujnu 2018. godine koje se provodilo u Referentnom centru za dijagnostiku i liječenje zaraze HIV-om u Klinici za infektivne bolesti u Zagrebu do prosinca 2022. Ispitanici su bili MSM ≥18 godina koji su koristili TDX/FTC i kod kojih su provedena testiranja na SPB: gonoreju, klamidijsku infekciju i sifilis. Ispitanici su na prvom pregledu ispunjavali upitnik kojim su ispitane njihove sociodemografske karakteristike i spolno ponašanje, a na kontrolnom pregledu su ispunjavali upitnik kojim se ispitivalo korištenje PrEP-a te spolno ponašanje. Izračunata je stopa incidencije za bakterijske SPB. Promjene u incidenciji bakterijskih SPB u prvoj i drugoj godini korištenja PrEP-a su iskazane omjerom stopa incidencije uz 95% intervale pouzdanosti (IP). Za longitudinalnu analizu korištena je Poissonova metoda opće procjene jednadžbe. Svi testovi provedeni su na razini statističke značajnosti od 5%. Od statističkih alata korišten je SAS 9.4 (SAS Institute, Cary, NC). Rezultati. U istraživanje je uključeno ukupno 570 ispitanika uz medijan dobi od 33,1 godinu. Prilikom uključenja u skrb za PrEP bakterijska SPB dijagnosticirana je u 146 (25,6%) ispitanika. Sifilis je dijagnosticiran u 35/570 (6,1%) ispitanika, gonoreja u 82/509 (16,1%) i klamidijska infekcija u 54/509 (10,6%) ispitanika. Ukupno je 331 ispitanik praćen tijekom prve godine korištenja PrEP-a, od čega je njih 220 praćeno i tijekom druge godine. Tijekom razdoblja praćenja zabilježeno je ukupno 335 epizoda bakterijskih SPB uz 456,9 osoba-godina praćenja (stopa incidencije: 73,3/100 osoba-godina [95%IP, 65,9-81,6]). U 176/331 (53,2%) ispitanika dijagnosticirana je neka bakterijska SPB (gonoreja: 106, klamidijska infekcija: 93 ispitanika i sifilis: 55 osoba). Stopa incidencije bakterijskih SPB u drugoj godini korištenja PrEP-a nije bila značajno viša u odnosu na prvu godinu (81,3/100 osoba-godina [95%IP, 68,8-96,0] vs. 68,6/100 osoba-godina [95%IP, 59,7-78,9]). Omjer stopa incidencije svih bakterijskih SPB tijekom druge i prve godine korištenja PrEP-a bio je 1,15 (95%IP, 0,92-1,44). Multivarijatna analiza pokazala je značajnu povezanost s pojavom bilo koje bakterijske SPB tijekom razdoblja praćenja za dob, broj učinjenih testova, nezaposlenost, ≥3 spolna partnera u posljednjih godinu dana, nekorištenje kondoma za vrijeme uzimanja PrEP-a te dijagnosticiranu bakterijsku SPB na inicijalnom pregledu. Sifilis je bio dijagnosticiran značajno češće 2020. i 2021. godine u odnosu na 2019., dok za druge SPB nisu utvrđene značajne razlike u odnosu na kalendarsku godinu. Zaključak. U istraživanju je utvrđeno da je stopa incidencije bakterijskih SPB u drugoj godini korištenja PrEP-a bila slična kao u prvoj godini. U više od polovice ispitanika je tijekom praćenja zabilježena neka SPB, najčešće gonoreja.Introduction. The use of antiretroviral drugs is part of the combined prevention strategy for HIV infection. The most commonly used drugs are tenofovir disoproxil fumarate/emtricitabine and generic formulations (TDX/FTC). Previous research on the incidence of sexually transmitted diseases (STDs) among pre-exposure prophylaxis (PrEP) users has shown different results. Aim. To assess the incidence of bacterial STDs during the first two years of PrEP use among men who have sex with men (MSM) in Croatia. The study also aimed to evaluate the prevalence of STDs at the initiation of PrEP and the factors associated with the occurrence of new STDs during the follow-up period. Methods. This is a retrospective and partially prospective observational cohort study conducted at the Reference Center for HIV Diagnosis and Treatment at the University Hospital for Infectious Diseases in Zagreb from September 2018 to December 2022. The study included MSM ≥18 years old who used TDX/FTC and were tested for STDs, including gonorrhea, chlamydia, and syphilis. At the initial visit, participants completed a questionnaire about their sociodemographic characteristics and sexual behavior. At the follow-up visit, they filled out a questionnaire regarding PrEP use and sexual behavior. The incidence rate of bacterial STDs was calculated. Changes in the incidence of bacterial STDs between the first and second year of PrEP use were expressed as incidence rate ratios with 95% confidence intervals (CIs). For longitudinal analysis, the Poisson generalized estimating equation method was used. All tests were conducted at a 5% level of statistical significance. SAS 9.4 (SAS Institute, Cary, NC) was used for statistical analysis. Results. A total of 570 participants were included in the study, with a median age of 33.1 years. At the initiation of PrEP care, bacterial STDs were diagnosed in 146 (25.6%) participants. Syphilis was diagnosed in 35/570 (6.1%) participants, gonorrhea in 82/509 (16.1%), and chlamydia in 54/509 (10.6%) participants. A total of 331 participants were followed during the first year of PrEP use, of which 220 were also followed during the second year. During the follow-up period, a total of 335 episodes of bacterial STDs were recorded, with 456.9 person-years of follow-up (incidence rate: 73.3/100 person-years [95% CI, 65.9-81.6]). A bacterial STD was diagnosed in 176/331 (53.2%) participants during the follow-up period (gonorrhea: 106, chlamydia: 93, and syphilis: 55 cases). The incidence rate of bacterial STDs in the second year of PrEP use was not significantly higher compared to the first year (81.3/100 person-years [95% CI, 68.8-96.0] vs. 68.6/100 person-years [95% CI, 59.7-78.9]). The incidence rate ratio of all bacterial STDs during the second year compared to the first year of PrEP use was 1.15 (95% CI, 0.92-1.44). Multivariate analysis showed a significant association with the occurrence of any bacterial STD during the follow-up period for age, the number of tests performed, unemployment, having ≥3 sexual partners in the past year, not using condoms while on PrEP, and a bacterial STD diagnosed at the initial visit. Syphilis was diagnosed significantly more often in 2020 and 2021 compared to 2019, while no significant differences were found for other STDs concerning the calendar year. Conclusion. The study found that the incidence rate of bacterial STDs in the second year of PrEP use was similar to that in the first year. More than half of the participants were diagnosed with an STD during the follow-up period, with gonorrhea being the most common

    Infections and sepsis in cardiac surgery patients

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    Infekcije i sepsa predstavljaju jedan od najsloženijih i najopasnijih izazova u skrbi za kardiokirurške bolesnike. Iako se teže infekcije javljaju kod relativno malog postotka pacijenata, značajno pogoršavaju ishode liječenja. Brojni čimbenici rizika, uključujući komorbiditete poput dijabetesa melitusa, prirodu samog kirurškog zahvata, primjenu izvantjelesnog krvotoka te nužnu imunosupresiju kod transplantacija srca doprinose njihovom nastanku. U prevenciji infekcija ključnu ulogu imaju strogo pridržavanje načela asepse, pravovremena primjena antibiotske profilakse i perioperativna kontrola glikemije. Među najčešćim uzročnicima dominiraju gram-pozitivne bakterije poput Staphylococcus aureus i koagulaza-negativni stafilokoki koji imaju sposobnost stvaranja biofilma na ugrađenim stranim materijalima. Značajnu ulogu imaju i gram-negativni patogeni poput Pseudomonas aeruginosa koji su često povezani s bolničkim okruženjem. Najčešće kliničke manifestacije uključuju infekcije sternalne rane i medijastinitis, infekcije povezane s intravaskularnim kateterima i uređajima za mehaničku cirkulacijsku potporu, pneumoniju povezanu s mehaničkom ventilacijom te urinarne infekcije. Sepsa, kao deregulirani odgovor domaćina na infekciju, dovodi do teške disfunkcije organa kroz složene patofiziološke mehanizme. Ovaj proces pokreće oslobađanje proupalnih medijatora, poznato kao ''citokinska oluja'', koja uzrokuje sistemsko oštećenje endotela i kapilarno popuštanje. Dijagnoza se temelji na ranom prepoznavanju kliničkih znakova, primjeni biomarkera, mikrobiološkoj te radiološkoj obradi, pri čemu ultrazvuk ima ključnu ulogu u procjeni hemodinamske nestabilnosti. Za objektivnu procjenu težine bolesti i disfunkcije organa koriste se standardizirane ljestvice poput SOFA bodovnog sustava. Liječenje zahtijeva brzu primjenu antimikrobne terapije, kontrolu izvora infekcije i hemodinamsku potporu. Ishod liječenja stoga ne ovisi samo o terapiji infekcije, već o primjeni preventivnih strategija i brzini prepoznavanja prvih znakova komplikacija.Infections and sepsis represent one of the most complex and dangerous challenges in the care of cardiac surgery patients. Although severe infections occur in a relatively small percentage of patients, they significantly worsen treatment outcomes. Numerous risk factors contribute to their development, including comorbidities such as diabetes mellitus, the nature of the surgical procedure itself, the use of cardiopulmonary bypass, and the necessary immunosuppression in heart transplantation. Strict adherence to aseptic principles, timely administration of antibiotic prophylaxis, and perioperative glycemic control play a key role in preventing infections. The most common causative agents are predominantly Gram-positive bacteria, such as Staphylococcus aureus and coagulase-negative staphylococci, which have the ability to form biofilms on implanted foreign materials. Gram-negative pathogens like Pseudomonas aeruginosa, often associated with the hospital environment, also play a significant role. The most common clinical manifestations include sternal wound infections and mediastinitis, infections related to intravascular catheters and mechanical circulatory support devices, ventilator-associated pneumonia, and urinary tract infections. Sepsis, as a dysregulated host response to infection, leads to severe organ dysfunction through complex pathophysiological mechanisms. This process triggers the release of pro-inflammatory mediators, known as a "cytokine storm," which causes systemic endothelial damage and capillary leak. Diagnosis is based on the early recognition of clinical signs, the use of biomarkers, microbiological and radiological workups, with ultrasound playing a key role in assessing hemodynamic instability. Standardized scales, such as the SOFA score, are used for the objective assessment of disease severity and organ dysfunction. Treatment requires the prompt administration of antimicrobial therapy, source control, and hemodynamic support. The treatment outcome, therefore, depends not only on the therapy of an established infection but crucially on the application of preventive strategies and the speed of recognition of the first signs of complications

    Epidemiology of myopia in the youth population

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    Kratkovidnost predstavlja najčešću refrakcijsku pogrešku kod djece i adolescenata te sve izraženiji globalni javnozdravstveni izazov. Nastaje kao posljedica nemogućnosti oka da fokusira paralelne svjetlosne zrake na mrežnicu, najčešće zbog aksijalne elongacije, a njezina učestalost u populaciji bilježi stalan porast, osobito u urbanim i visokorazvijenim sredinama. Etiologija kratkovidnosti je multifaktorijalna i uključuje genetske predispozicije te brojne okolišne čimbenike, među kojima se osobito ističu produljeni rad na blizinu, smanjena izloženost prirodnom svjetlu, prekomjerna uporaba digitalnih uređaja, nedostatak tjelesne aktivnosti i poremećaji u obrascima spavanja. Epidemiološki podaci ukazuju na značajne razlike u prevalenciji kratkovidnosti ovisno o dobi, spolu, geografskoj regiji i stupnju urbanizacije, pri čemu djeca školskog uzrasta predstavljaju skupinu najvišeg rizika za razvoj i progresiju bolesti. Dijagnostički pristup uključuje procjenu vidne oštrine, objektivna i subjektivna refrakcijska mjerenja, cikloplegičnu refrakciju, biometrijsko mjerenje aksijalne duljine te slikovne metode vizualizacije stražnjeg segmenta oka. Liječenje i kontrola progresije kratkovidnosti obuhvaćaju primjenu optičkih metoda poput multifokalnih naočala i kontaktnih leća, farmakološke intervencije niskim dozama atropina te modifikaciju životnih navika usmjerenih na povećanje boravka na otvorenom i smanjenje vremena provedenog pred ekranima. Posebna pozornost posvećena je važnosti ranog prepoznavanja rizičnih čimbenika i provođenju javnozdravstvenih strategija koje uključuju preventivne programe, edukaciju roditelja i učitelja te uspostavu sustavnog praćenja refrakcijskog statusa djece, s ciljem smanjenja budućeg opterećenja visokim stupnjem kratkovidnosti i njezinim ozbiljnim komplikacijama poput ablacije mrežnice, glaukoma i miopijske makulopatije. Pravodobno prepoznavanje problema i integracija učinkovitih preventivnih i terapijskih mjera ključni su za očuvanje vidne funkcije i smanjenje dugoročnog tereta bolesti u populaciji djece i mladih.Myopia is the most common refractive error among children and adolescents and represents an increasingly significant global public health challenge. It occurs as a result of the eye’s inability to focus parallel light rays onto the retina, most commonly due to axial elongation, and its prevalence continues to rise, particularly in urban and highly developed regions. The etiology of myopia is multifactorial, involving genetic predisposition and numerous environmental factors, with prolonged near work, reduced exposure to natural light, excessive use of digital devices, lack of physical activity, and sleep pattern disturbances being especially prominent. Epidemiological data indicate substantial differences in the prevalence of myopia depending on age, gender, geographical region, and degree of urbanization, with school-age children representing the highest-risk group for the development and progression of the condition. Diagnostic approaches include assessment of visual acuity, objective and subjective refraction measurements, cycloplegic refraction, biometric measurement of axial length, and imaging techniques for visualization of the posterior segment of the eye. Treatment and control of myopia progression encompass the use of optical methods such as multifocal spectacles and contact lenses, pharmacological interventions with low-dose atropine, and lifestyle modifications aimed at increasing outdoor activities and reducing screen time. Particular attention is given to the importance of early identification of risk factors and the implementation of public health strategies, including preventive programs, education of parents and teachers, and the establishment of systematic monitoring of children's refractive status, with the goal of reducing the future burden of high myopia and its serious complications such as retinal detachment, glaucoma, and myopic maculopathy. Timely recognition of the problem and the integration of effective preventive and therapeutic measures are crucial for preserving visual function and reducing the long-term burden of disease among children and young people

    What do we know about COVID vaccines

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    Pandemija COVID-19, uzrokovana virusom SARS-CoV-2, zahtijevala je brzi razvoj cjepiva. Razvijene su različite vrste cjepiva, sve s ciljem poticanja imunološkog odgovora. mRNA cjepiva, poput Pfizera i Moderne, pokazala su najveću učinkovitost. Cijepljenje je preporučeno svim osobama starijim od 6 mjeseci, osobito rizičnim skupinama. Unatoč mogućim nuspojavama, korist od cijepljenja višestruko nadmašuje potencijalne rizike te značajno smanjuje smrtnost i težinu bolesti. Centar za kontrolu i prevenciju bolesti preporučuje da se djeca mlađa od 5 godina, ukoliko prethodno nisu cijepljena, cijepe mRNA cjepivima – Moderna u dvije, a Pfizer u tri doze, s propisanim razmacima. Za djecu od 5 do 11 godina dovoljna je jedna doza, bez obzira na prethodnu imunizaciju. Osobe od 12 do 64 godine primaju jednu dozu, dok se starijima od 65 preporučuju dvije. Imunokompromitirani trebaju tri doze, uz najnoviju formulaciju cjepiva. Hrvatski zavod za javno zdravstvo preporučuje slične smjernice, uz naglasak na docjepljivanje starijih, kroničnih bolesnika i imunokompromitiranih, s razmacima prilagođenima dobi i zdravstvenom statusu. Cjepiva protiv SARS-CoV-2 mogu uzrokovati blage i prolazne lokalne i sistemske nuspojave poput boli na mjestu uboda, umora, glavobolje i vrućice. Rijetko se javljaju ozbiljne reakcije poput vazovagalne sinkope i anafilaksije, koja je jedina apsolutna kontraindikacija za daljnje cijepljenje. Alergije na sastojke poput polietilen glikola ili polisorbata zahtijevaju individualan pristup. Učinkovitost cjepiva slabi s vremenom i novim varijantama. Booster doze djelomično vraćaju zaštitu. Miokarditis je rijetka nuspojava mRNA cjepiva, a češća je kod mladih muškaraca. Neka cjepiva (AstraZeneca, Janssen) povučena su zbog slučajeva tromboze. Pandemija je istaknula važnost povjerenja u znanost, borbe protiv dezinformacija i daljnjeg razvoja sezonskih cjepiva.The COVID-19 pandemic, caused by the SARS-CoV-2 virus, required the rapid development of vaccines, all aimed at stimulating an immune response. mRNA vaccines, such as Pfizer and Moderna, proved to be the most effective. Vaccination is recommended for all individuals over 6 months of age, especially those in high-risk groups. Despite possible side effects, the benefits of vaccination far outweigh the potential risks and significantly reduce mortality and disease severity. Centers for Disease Control and Prevention recommends that children under 5 years of age who have not been previously vaccinated receive mRNA vaccines – two doses of Moderna or three doses of Pfizer, with prescribed intervals. For children aged 5 to 11, a single dose is sufficient, regardless of prior immunization. Individuals aged 12 to 64 receive one dose, while those over 65 are advised to get two. Immunocompromised persons should receive three doses, using the latest vaccine formulation. Croatian Institute of Public Health issues similar guidelines, emphasizing booster doses for the elderly, chronically ill, and immunocompromised, with dosing schedules adjusted by age and health status. SARS-CoV-2 vaccines may cause mild and temporary local or systemic side effects, such as injection site pain, fatigue, headache, and fever. Serious reactions, e.g. vasovagal syncope and anaphylaxis, are rare; anaphylaxis remains the only absolute contraindication for further vaccination. Allergies to components like polyethylene glycol or polysorbate require an individualized approach. Vaccine effectiveness decreases over time and with the emergence of new variants, but booster doses help restore some protection. Myocarditis is a rare side effect of mRNA vaccines, more commonly seen in young males. Some vaccines (AstraZeneca, Janssen) were withdrawn due to cases of thrombosis. The pandemic highlighted the importance of trust in science, combating misinformation, and continuing the development of seasonal vaccines

    Basal insulin treatment in type 2 diabetes

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    Šećerna bolest tipa 2 jedna je od najčešćih kroničnih bolesti suvremenog doba, čineći otprilike 90–95 % svih slučajeva šećerne bolesti. Temeljni mehanizmi uključuju inzulinsku rezistenciju i neadekvatan odgovor β-stanica gušterače. Epidemiološki podaci pokazuju stalan porast prevalencije, osobito u razvijenim zemljama, ali i u onima u razvoju. Liječenje u ranoj fazi bolesti temelji se na promjenama životnog stila i primjeni oralnih antidijabetika. Međutim, zbog progresivne prirode bolesti, često je potrebno uvesti inzulinsku terapiju, pri čemu bazalni inzulin predstavlja temelj liječenja tipa 2 šećerne bolesti. Prednost primjene bazalnog inzulina u odnosu na druge terapijske pristupe leži u jednostavnosti režima, mogućnosti samostalne titracije doze od strane pacijenta, rijetkoj pojavi hipoglikemije te minimalnom povećanju tjelesne mase. Bazalni inzulin prvenstveno djeluje na suzbijanje prekomjerne hepatičke proizvodnje glukoze, čime se postiže stabilizacija glikemije između obroka i tijekom noći. Postoje različiti tipovi bazalnih inzulina - od NPH inzulina, preko dugodjelujućih pripravaka poput glargina U100 i detemira, do novijih formulacija poput glargina U300, degludeka i icodeca - koji se razlikuju po farmakokinetici, farmakodinamici, trajanju i profilu djelovanja te potrebi za titracijom. Prednost dugodjelujućih bazalnih inzulina u odnosu na druge vrste inzulina leži u postizanju stabilnije kontrole glikemije, uz smanjen rizik od hipoglikemije i manjim utjecajem na porast tjelesne mase. Titracija doze ključna je za postizanje i održavanje optimalne glikemijske kontrole, uz istodobnu prevenciju hipoglikemija. Edukacija pacijenata koji su na inzulinskoj terapiji iznimno je važna jer doprinosi boljoj regulaciji glikemije, povećava adherenciju te smanjuje rizik od komplikacija, uključujući lipohipertrofiju.Type 2 diabetes is one of the most prevalent chronic diseases of modern times, accounting for approximately 90–95% of all diabetes cases. It is primarily driven by insulin resistance and an inadequate response of pancreatic β-cells. Epidemiological data show a steady increase in disease prevalence, especially in developed countries and developing regions. Initial treatment focuses on lifestyle modifications and oral antidiabetic medications. However, due to the progressive nature of the disease, insulin therapy is often required over time, with basal insulin forming the cornerstone of treatment in type 2 diabetes. The advantage of using basal insulin over other types of therapy lies in the simplicity of the regimen, the possibility of self-titration by the patient, the lower risk of hypoglycemia, and minimal weight gain. Basal insulin primarily works by suppressing excessive hepatic glucose production, thereby regulating blood glucose levels between meals and overnight. Various types of basal insulins are available - from NPH insulin and long-acting analogues such as glargine U100 and detemir, to advanced formulations like glargine U300, degludec, and icodec - each offering unique pharmacokinetic and pharmacodynamic characteristics, including action duration and titration needs. Long-acting basal insulins have advantages over other insulin types, including more stable glycemic control, reduced risk of hypoglycemia, and less weight gain. Dose titration is crucial for achieving and maintaining optimal glycemic control while minimizing the risk of hypoglycemia. Patient education is a key component of care for those on insulin therapy, as it leads to improved glycemic outcomes, better adherence, and a lower incidence of complications such as lipohypertrophy

    Neuropsychiatric manifestations in patients with systemic lupus erythematosus

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    Sustavni eritemski lupus (SLE) kronična je autoimunosna bolest vezivnoga tkiva koja može zahvatiti bilo koji organski sustav ili tkivo. Neuropsihijatrijski SLE (NPSLE) pojam je koji se odnosi na direktno zahvaćanje živčanoga sustava sistemskim lupusom. Manifestira se kao neki od 19 sindroma opisanih od Američkog reumatološkog društva (ACR, prema eng. American College of Rheumatology) 1999. godine. Najčešće je zahvaćen središnji živčani sustav što se manifestira kao glavobolja, kognitivna disfunkcija, anksiozni poremećaj, poremećaj raspoloženja, cerebrovaskularna bolest, epilepsija, psihoza, akutno konfuzno stanje, demijelinizacijski poremećaj, mijelopatija, aseptički meningitis ili poremećaj pokreta. Zahvaćenost perifernog živčanog sustava očituje se kao polineuropatija, mononeuropatija, kranijalna neuropatija, autonomni poremećaj, Guillain-Barréov sindrom, mijastenija gravis ili pleksopatija. NPSLE je, zbog manjka saznanja o njegovoj patogenezi, nedostatka specifičnih biomarkera, složene kliničke slike i nedovoljnoga broja kliničkih studija, izazov za dijagnosticiranje i liječenje.Systemic lupus erythematosus (SLE) is a chronic autoimmune connective tissue disease that affects various organ systems and tissues. Neuropsychiatric SLE (NPSLE) refers to the direct involvement of the nervous system in SLE, manifesting as one of 19 syndromes identified by the American College of Rheumatology (ACR) in 1999. The central nervous system is most frequently affected, with presentations including headache, cognitive dysfunction, anxiety disorders, mood disorders, cerebrovascular disease, seizure disorder, psychosis, acute confusional state, demyelinating syndromes, myelopathy, aseptic meningitis and movement disorders. Peripheral nervous system involvement may present as polyneuropathy, mononeuropathy, cranial neuropathy, autonomic disorders, Guillain-Barré syndrome, myasthenia gravis and plexopathy. Due to limited understanding of its pathogenesis, a lack of specific biomarkers, complex clinical manifestations, and a limited number of clinical studies, NPSLE remains a significant challenge for diagnosis and treatment

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