Environmental heat stress disrupts cellular homeostasis through coordinated molecular responses involving protein quality control, oxidative stress regulation, inflammatory signaling, and water homeostasis. Although saliva plays an essential role in maintaining oral homeostasis, the molecular pathways underlying salivary adaptation to heat stress remain insufficiently characterized. We hypothesized that integrating the human salivary proteome with systems biology approaches would identify a reproducible heat-stress-responsive molecular signature. Human salivary proteomic datasets retrieved from the Human Salivary Proteome Wiki were integrated into a non-redundant dataset comprising 15,594 protein accessions corresponding to 2540 distinct proteins. Following deduplication, functional annotation, and biological curation, proteins associated with heat stress response, oxidative stress regulation, inflammatory signaling, water homeostasis, salivary secretion, and mucosal protection were assembled into a Salivary Climate Stress Panel (SCSP). Protein–protein interaction and functional enrichment analyses were performed, and the biological relevance of the identified proteins was independently evaluated using a human heat stress transcriptomic meta-analysis comprising 322 comparisons and the GEO dataset GDS3004. Functional filtering identified 2050 heat-stress-associated salivary proteins, from which a curated SCSP of 35 proteins was established. Network analysis identified HSP90AB1, HSP90AA1, and IL1B as the principal hub proteins linking heat stress, oxidative stress, inflammatory signaling, and water homeostasis pathways, while transcriptomic validation confirmed consistent activation of representative SCSP genes under heat stress conditions. These findings provide a reproducible systems-level framework for investigating heat-stress-responsive molecular pathways in the human salivary proteome and support future studies on salivary biomarkers of environmental heat exposure.
Introduction: Congenital heart defects (CHDs) are the most frequent group of major congenital anomalies and impose a disproportionate burden on neonatal services. Antenatal detection determines where and how an affected newborn is delivered, yet reported detection rates differ several-fold between European countries. We aimed to quantify the postnatal occurrence and the antenatal detection of CHDs in a tertiary obstetric center in Western Romania and to place both figures in a comparable international context. Material and Methods: Retrospective observational study of all 10,113 births registered at the “Pius Brînzeu” County Clinical Emergency Hospital, Timișoara, between 2018 and 2022. Newborns with at least one cardiac lesion recorded on indication-based postnatal echocardiography were identified from the hospital electronic record. Interatrial communications and ductal patency recorded at the neonatal-index examination were counted inclusively and are analyzed separately from structural defects. A defect was classified as antenatally detected when it had been reported at any prenatal ultrasound scan and was subsequently confirmed postnatally. Proportions are reported with Wilson score 95% confidence intervals (CIs), separately at the level of the newborn and at the level of the individual lesion. Results: A total of 541 newborns carried at least one recorded cardiac lesion, giving an occurrence of 5.35% of births (95% CI 4.93–5.81); 670 individual lesions were recorded, a mean of 1.24 per affected newborn. Interatrial communication (n = 319; 47.6% of lesions) and ductal patency (n = 90; 13.4%) accounted for 61.0% of lesions; among the 261 structural defects, ventricular-septal defect was the most frequent (n = 121; 46.4%). An antenatal diagnosis had been made in 151 of 541 newborns (27.9%; 95% CI 24.3–31.8). Detection was highest for lesions distorting the four-chamber view, hypoplastic left-heart syndrome 4/5, and ventricular septal defect 80/121 (66.1%; 95% CI 57.3–73.9), and lowest for lesions requiring outflow-tract or arch views, including pulmonary stenosis 3/27 (11.1%; 95% CI 3.9–28.1) and aortic stenosis 0/12. Restricting the count to structural defects gives 13.1 to 25.8 affected newborns per 1000 births, against a EUROCAT total prevalence of 8.0 per 1000. Conclusions: The occurrence recorded here reflects tertiary referral, indication-based echocardiography, and an inclusive case definition rather than a genuine population excess, and is not interchangeable with registry prevalence. The antenatal detection rate of 27.9% sits between European settings without organized screening and those performing two or three routine scans per pregnancy. The detection deficit is concentrated in lesions that require outflow-tract or arch views. Because the views obtained at each scan were not recorded and detection was not stratified by prenatal-care status, the contribution of examination protocol and of access to care is inferred rather than demonstrated; both are testable hypotheses for a prospective, protocolized study.
Background/Objectives: Oral diseases are among the most prevalent non-communicable diseases and impose a substantial public health burden across Europe. Although general total health expenditure may reflect health-system capacity, it does not specifically measure oral healthcare financing, and evidence regarding its association with population-level oral health remains limited. The objective of this study was to assess the association between total health expenditure and oral health outcomes in European countries. The primary focus was on dental caries prevalence, while a secondary exploratory analysis examined edentulism. Methods: Using publicly available international databases, an ecological, unbalanced country-level panel dataset was constructed. The main caries model included 153 country-year observations from 25 European countries during 2015–2021. An extended model incorporating practicing dentist density included 109 observations from 20 countries. Two-way fixed-effects regression models with country and year effects and country-clustered standard errors were applied. Edentulism was examined using exploratory cross-sectional OLS models for 2019. Results: In the main model, higher total health expenditure (β = −0.00305, p = 0.027) and GDP per capita (β = −0.00024, p = 0.021) were associated with lower caries prevalence. In the extended model, only GDP per capita remained statistically significant (β = −0.00028, p = 0.021), whereas total health expenditure, tertiary educational attainment, and practicing dentist density were not significantly associated with caries prevalence. No statistically significant associations were observed in the exploratory edentulism analyses. Conclusions: Total health expenditure and GDP per capita were negatively associated with caries prevalence in the main country-level model, although the expenditure association was not maintained in the restricted extended sample. These ecological findings do not establish causality and require confirmation using more complete, oral-health-specific data.