Institute for Medical Research and Occupational Health

We present the report of disease in a child with severe restrictive cardiomyopathy (RCM) resulting in the development of veno-occlusive pulmonary arterial hypertension (PAH) and cardiopulmonary insufficiency with NYHA II-III. Due to borderline criteria for heart transplantation (HT), it was difficult to find justification for the procedure, although it was the only way to save the child’s life. The boy was monitored for hepatomegaly one year before admission. At the age of 11, significant dilatation in both atria, accompanied by a reduced cavity of both ventricles led to the recognition that the clinical symptoms were attributed to restrictive cardiomyopathy (RCM) with preserved left ventricular ejection fraction (LVpEF – LV with preserved EF). Because of the evidence suggesting that it is a secondary development of veno-occlusive PAH, before the HT decision it was required to clarify distinguish from reactive PH, in accordance with the latest 6WSPH criteria (6th World Symposium on pulmonary hypertension) [1]. Pulmonary hypertension is considered when the mean pulmonary artery pressure (mPA) is >20 mmHg, transcapillary gradient (PAWP) > 15 mmHg and pulmonary vascular resistance (PVR) ≥ 3 iWJ. Since the patient did not meet the criteria for passive (isolated) precapillary PAH (mPA>20 mmHg, PAWP >15 mmHg and PVR < 3iWJ) with preserved LVEF /IpcPH/LVpEF=Isolated precapillary PH with LVpEF/, but according to the same criteria, he had reactive, or combined veno-occlusive pulmonary hypertension (PVR ≥ 3iWJ) /CpcPH/LVpEF= Combined precapillary PH with LV preserved EF)/. Diagnosis indicated that it was a contraindication for HT. This position is valid only if the discussion about possible reversible changes in PAS (Pulmonary artery small – the former name of arteriole) are ignored. Aware of the fact that HT is risky, but also of the probability that changes caused by the Kitajew phenomenon are reversible [2] contrary to precapillary PH caused by CHD (Euler Ljiljestrand fenomen) [3], we decided to proceed with HT. We are predicting a difficult postoperative course but which can be overcome with adequate measures (strict supervision of the Frank-Starling law) [4] with mechanical and pharmacology support. Encouraged by reports from the literature indicating a significantly higher incidence of passive postcapillary than reactive pulmonary hypertension as well as rapid regression of pulmonary hypertension after elimination of the cause of PAS self perpetuation [5-7], we decided on HT as the only perspective for the survival of a severely ill child. Our arguments also included a discussion on the irreversibility of PAH before the development of Eisenman’s syndrome (ES) (“gray area”, 6-8 iWJ) [8,9]. HT decision despite the inconsistency of the criteria for defining pulmonary hypertension and the type of pulmonary vascular resistance according to the previous international criteria’s [10-13], including the 6WSPH criteria [1,8,14,15]. Our arguments were accepted by the EUROTRANSPLANT committee. A HT was successfully performed and boy was discharged home with good follow up more than > 10 years in good condition (NYHA I).

Machine learning (ML) models can complement traditional measurement-based approaches by supporting large-scale screening, spatial analysis, and prioritization of buildings for testing of indoor radon, a leading cause of lung cancer among non-smokers. Originating from uranium decay in soil and rock, radon enters homes via foundation cracks and accumulates indoors, influenced by building characteristics, ventilation, urbanization, and geogenic factors. As part of the Zagreb pilot within the “Evidence Driven Indoor Air Quality Improvement” (EDIAQI) project, this is the first ML application for indoor radon analysis in Croatia. This research evaluates residential indoor radon concentrations in Zagreb using ML applied to a dataset of 80 households. Several linear regression and tree-based ensemble methods were tested. The best-performing model (GBR) achieved an R2 of 0.99 on the training set and 0.57 on the test set, with an RMSE of 33 Bq/m3 and MAE of 26 Bq/m3. Although predictive performance was moderate and generalization limited, key building characteristics such as construction year, dwelling type, occupancy details, and floor level were identified as relevant variables. The results suggest that machine learning may support radon risk prioritization in urban environments, but cannot replace direct measurements for regulatory purposes.

Toxic heavy metals, including cadmium (Cd) and lead (Pb), can build up in placental tissue or pass through the placental barrier, potentially harming fetal development. Therefore, the placenta can serve as a useful tool for assessing prenatal exposure to these harmful substances. Over the past several decades, Croatia has implemented a range of environmental and public health measures aimed at reducing exposure to Cd and Pb, including ratification of the World Health Organization Framework Convention on Tobacco Control (FCTC), ban on smoking in public places, intensified health education campaigns, and the complete phase-out of leaded gasoline in 2006. As a result, smoking prevalence among women and Pb levels in ambient air have declined substantially. This study reviews and analyzes existing literature on Cd and Pb levels in placental tissue of women in Zagreb, Croatia, in order to evaluate the effectiveness of these health and environmental policies and to identify persistent or emerging risks associated with toxic metal exposure during pregnancy by comparing placental Cd and Pb levels between smokers and nonsmokers across several time periods.

BackgroundPrevious research has identified that, in individuals with lower folate and/or vitamin B12 levels, homocysteine is associated with specific elements, while amino acids are associated with folate, thereby influencing folate availability during supplementation. This study investigates the impact of the MTHFR 677C/T polymorphism on levels of these compounds in individuals with differing meat consumption preferences, non-vegetarians and vegetarians.MethodsThe study was conducted on 162 Croatian subjects. MTHFR gene polymorphism was determined by PCR-RFLP, elements by ICP-QQQ, amino acids by GC–MS, and biochemical parameters by chemiluminescent immunoassay and enzymatic methods. Differences between the groups were tested by ANOVA, while associations between the parameters were examined by multiple regression analyses.ResultsThe CT + TT genotype had lower folate levels in comparison to the CC genotype. The influence of MTHFR 677C/T polymorphism on element levels was limited to Al and Ca: individuals with the CT + TT genotype exhibited higher plasma Ca levels than the wild-type (CC) genotype, while lower plasma Al values were observed only in vegetarians with the CT + TT genotype. The CT + TT genotype was also associated with higher levels of glutamic acid, proline, glycine (only in vegetarians), and aspartic acid.ConclusionAlthough we observed an effect of the MTHFR 677C/T polymorphism on folate, certain elements and amino acid levels, further research is required to validate our findings and establish a more comprehensive understanding of the link between elements, amino acids and the MTHFR gene polymorphism.

One of the major hallmarks of Alzheimer’s disease (AD), deposition of amyloid plaques in the brain, arises from the proteolytic processing of the amyloid precursor protein (APP), a process in which the rate-limiting step is carried by β-secretase (BACE1). Due to this essential role in the development of AD, BACE1 has become a widely studied drug target for the development of new drugs aimed at blocking amyloid β peptide formation and aggregation through inhibition of BACE1 activity. The development of the first BACE1 inhibitors allowed the determination of its crystal structure and description of its active site, confirming the existence of eleven well-defined subsites able to accommodate a range of substrates, which enabled BACE1 to participate in a number of biological processes. For this reason, the study of BACE1 structure and determination of specific structural motifs responsible for the accommodation of known substrates could enable defining drugs with very specific targets, as well as provide insight into the mode of action of BACE1 itself. This review will focus on the overall structure of BACE1 and its active site, as well as on the effect of genetic polymorphisms and isoforms on its activity.

HighlightsWhat are the main findings?The prevalence of overweight (including obesity) steadily increased over time, particularly until the mid-2010s, whereas the prevalence of severe obesity had the opposite trend throughout.The lowest prevalence rates of overweight and obesity were observed in the capital, with other regions exhibiting significantly higher risks.What is the implication of the main finding?Despite a slowdown in the growth of overweight (including obesity) prevalence in recent years, Croatia has yet to reach the plateau observed in some other European countries.Regional differences in the overweight and obesity risk require a follow-up.Background: Childhood obesity remains a significant public health challenge globally. Croatia ranks among the leading European countries in terms of childhood overweight and obesity prevalence. Methods: The present cross-sectional study analysed overweight and obesity prevalence trends from 2003 to 2022 on a nationally representative sample containing data from five studies, two independent studies and three WHO COSI rounds. Data from a total of 11,817 children aged 7.00–8.99 were analysed. Weight categories were defined using the IOTF and WHO cut-offs. Overweight and obesity prevalence rates and trends overall and by sex and region were calculated, and binary regression models applied to investigate the relationship between the risk of overweight and several variables. p-value < 0.05 was used to define statistical significance. Results: Temporal trends and associations were investigated using the IOTF reference values. The prevalence of overweight (including obesity) had increased steadily from 2003 to 2015, thereafter continuing to increase at a slower rate, whereas the prevalence of severe obesity reduced over time. Even though boys had slightly higher prevalence rates of overweight, the growth in overweight prevalence in girls over time was significant. At the regional level, the lowest prevalence rates were detected in the capital (City of Zagreb region). The risk of overweight was at least 50% higher in all the other regions in Croatia, and a rising trend in overweight risk with time was particularly high among children in the Adriatic and Northern regions. Conclusions: Despite a deceleration in the rate of increase in overweight (including obesity) prevalence, Croatia is yet to reach a plateau observed in some other European countries. Unearthed regional differences warrant further investigation.

Young people often use headphones or speakers and most visit noisy places recreationally. The aim of this cross-sectional study was to determine the relationship between exposure to recreational noise and hearing in 108 young Croatian participants aged 18–28 years. Hearing was assessed with audiometry and noise exposure by measuring the headphone volume to which each participant was accustomed while listening to music. Data on the daily use of headphones/speakers, visits to recreational noisy places, self-assessment of hearing, and health and demographics data were obtained with a questionnaire developed for this purpose. Mild sensorineural hearing loss was found in 5.5 % of participants (one man and six women). While all men reported their hearing as good, 13.9 % of women (n=9) described their hearing as average. Those women had significantly higher hearing thresholds than women who rated their hearing as good (p=0.036). Men spent significantly more time using headphones/speakers than women (1.9±1.2 vs 1.3±0.8 hours, p=0.002). Both men and women spent similar amount of time in recreational noisy venues, averaging 12.0 hours per month. More men used headphones at volumes exceeding 70 dB than women (52.2 % vs 27.7 %, p=0.009). Participants who self-reported hearing loss had significantly higher hearing thresholds than those who did not (p=0.036). Although we found no clear link between recreational noise and hearing loss, elevated thresholds in participants who reported hearing difficulties highlight the need for targeted hearing loss prevention.