Objectives:The study aimed to provide a comparative analysis of HRQoL and its health-related and socio-demographic correlates among Ukrainian refugees and general population in Estonia. Methods:Study used age and sex matched data (1249 pairs) from two representative cross-sectional surveys covering Ukrainian refugees aged 18-64 years residing in Estonia (n = 1,430), and the general population (n = 2007) of Estonia in 2024. Tobit-regression was used to compare the EQ-5D-3L index values in both groups while controlling for wide range of socio-demographic and health indicators. Results:Refugees reported less restrictions in mobility, self-care or in performing usual activities, whereas higher prevalence of pain/discomfort and anxiety/depression was found for refugees compared to control group. Refugees had slightly lower EQ-5D index score (estimate -0.017, p = 0.029) compared to population controls after adjustment for socio-demographic and health-related covariates. Conclusion:Variations in EQ-5D-3L dimensions and index scores between refugees and population controls contribute to the literature on refugee HRQoL and extend the knowledge on HRQoL of Ukrainian refugees in the context of ongoing refugee crisis in Europe while also improving knowledge for support provision to this refugee group in Estonia.
Longitudinal studies on population representative samples offer unique insights. The Estonian Children Personality Behaviour and Health Study (ECPBHS; EstChild) was launched in 1998 on two birth cohort samples at age 9 or 15 with an exceptional participation rate, has been monitored at ages 15, 18, 25 and 33, and also recruited parents of the target subjects. This multidisciplinary investigation has been focused on behavioural neuroscience, illuminating findings on what could be discerned from biomarkers, candidate genes, gene × environment interactions, and epigenetic markers in representative samples, and in birth cohorts living through societal transformation. ECPBHS analysed how biomarkers and lifestyle are associated with real-life behaviours and developmental trajectories, phenotypes such as neuroticism, bulimia, aggressiveness or attention deficit, and outcomes from incidence of psychiatric disorders to the obtaining of university education. Novel evidence has been observed on clustering of fears and the inner structure of impulsivity and reward sensitivity, together with clues how these may have co-emerged with metabolic types. New insights have been provided to understand the classic biomarkers, cholesterol and platelet monoamine oxidase activity, as well as several functional gene variants. Hypotheses how to synthetise molecular genetics and sociology, how sex or gender matters in the light of gene × environment interactions and how family and parental roles shape the behaviour of offspring have been put forward. The ECPBHS has offered clues on why in biological psychiatry many replication attempts are predestined to fail, and how to learn from such failures.
Effective cervical cancer screening and progress toward WHO elimination targets depend on complete follow-up for women with positive primary screening tests. However, real-world data on this critical step in hrHPV-based screening programs in Eastern Europe are scarce. We conducted a nationwide, population-based retrospective cohort study in Estonia, analyzing records from the Estonian Health Insurance Fund and Population Register. We included 44,282 women aged 30-65 who were invited to hrHPV-based screening between January 1, 2021, and December 31, 2022, with follow-up through March 31, 2024. Screening attendance was 45.7% (n = 20,242; 95% CI: 45.2%-46.2%), with 8.0% (n = 1615; 95% CI: 7.6%-8.4%) testing hrHPV-positive. A substantial loss to follow-up was observed: 57.7% of hrHPV-positive women did not undergo repeat hrHPV testing, colposcopy, or any post-colposcopy care within 12 months. Among those referred for further diagnosis, colposcopy was performed in 77.9% within 6 months. Treatment for High-Grade Squamous Intraepithelial Lesion (HSIL) cases was high (85.5%; n = 124; 95% CI: 78.7%-90.5%), mostly within 3 months. Predictors of lower follow-up adherence included older age and residence in South Estonia. Suboptimal screening uptake and high loss to follow-up among hrHPV-positive women are significant barriers to effective cervical cancer prevention in Estonia. These challenges mirror those seen in many organized screening programs globally. Prioritizing strategies to enhance follow-up adherence is critical for timely diagnosis and treatment, ultimately accelerating global efforts toward cervical cancer elimination.
Immune checkpoint inhibitors (ICIs) combined with chemotherapy represent a standard first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). While their clinical benefit is well established, the tumour-intrinsic effects of ICIs on chemotherapy responses remain incompletely understood. Given the biological differences between HPV-positive and HPV-negative HNSCC, including divergent TP53 status and stress-response signalling, we investigated whether ICIs directly modulate chemotherapeutic efficacy in tumour cells independent of immune components. Two well-characterized HNSCC cell lines were used: FaDu (HPV-negative, TP53-mutant) and SCC090 (HPV-positive, TP53 wild-type). Cells were treated with clinically relevant concentrations of pembrolizumab or nivolumab in combination with cisplatin, 5-fluorouracil (5-FU), paclitaxel, docetaxel, or etoposide and viability was assessed using resazurin-based assay. Both ICIs significantly altered the potency of several chemotherapeutic agents in a drug- and cell line-dependent manner. Validation of the selected trends by immunofluorescence analysis of TP53 and phospho-Ser10 histone H3 (pS10H3) revealed that paclitaxel potentiation by nivolumab in FaDu cells was associated with reduced TP53 and pS10H3 levels, whereas 5-FU depotentiation by both ICIs correlated with increased TP53 and shifts in the cell cycle. Additionally, spheroid formation assay demonstrated enhanced disruption of cell-cell adhesion for paclitaxel combination with nivolumab compared to the cytostatic drug alone. Together, these findings suggest that ICIs modulate tumour-intrinsic stress responses involving TP53 signalling, cell cycle regulation, replication stress, and adhesion dynamics. These interactions are context-dependent and appear to vary according to drug class, TP53 status, and HPV background. Our findings underscore the importance of integrating HPV status and TP53 biology into future precision treatment strategies.
Recent studies have suggested the involvement of brain RNA m(6)A methylation in stress response. One of the key players in the RNA m(6)A regulation is the demethylation catalysed by the fat mass and obesity-associated protein FTO, encoded by the fat mass and obesity-associated gene. Based on findings that experimental manipulation of the RNA m(6)A methylation in animal experiments can affect anxiety, and given that the C-allele of FTO rs1421085 had a significant association with indicators of overweight and obesity in our previous study, we have examined the possible association of FTO rs1421085 genotype with neuroticism in the same longitudinally observed sample. Data analysis included both birth cohorts of the Estonian Children Personality, Behaviour and Health Study (ECPBHS) that started in 1998/1999 when participants were 9 or 15 years old, respectively. Follow-ups were conducted at age 15, 18 and 25. Neuroticism at different ages was assessed with questionnaires of the five factor model. Statistically significant assocation between the FTO rs1421085 genotype and neuroticism emerged by age 25, with an additive effect of each T-allele. This association was largely based on females and was prominent in the older birth cohort at age 25, sampled during the Great Recession of 2007-2009. Conclusively, an overweight and obesity-related variant of FTO, the gene encoding an RNA m(6)A demethylase, was associated with lower neuroticism, this association being subject to gender and cohort effects.
