Mapping Early Childhood Caries Prevention Programmes in Scotland and South-Eastern Europe

Background: Early Childhood Caries (ECC) is a recognised global public health challenge, and the World Health Organisation (WHO) has set out preventive approaches in an implementation manual. Scotland has an established information-sharing partnership with countries in South-Eastern Europe, where the ECC burden is substantial. Aim: This project aimed to map ECC and preventive programmes in Scotland and South-Eastern Europe against WHO criteria and to facilitate discussion, drawing from recent research and assessment of international consensus, to agree on priority interventions. Methods: A dedicated pro-forma gathered structured information on: population statistics; disease burden; workforce capacity; interventions in dental practice, early years education and the community. A recorded online workshop involved presentations and discussions of policy and practice in relation to current and future ECC prevention plans. Workshop discussions were transcribed and analysed using thematic theory-based implementation frameworks, facilitated by QSR NVivo12.0 software. Results: Data were received from Albania, Bulgaria, Croatia, Romania, Scotland and Serbia. The child population and birth rate are generally declining. In 2019, ECC prevalence among 5–6-year-olds was 80% to 84% in South-Eastern Europe countries, while in Scotland, less than a third (26%) of those children had obvious decay experience in their primary teeth in 2020, compared with more than half (55%) in 2003. A key barrier for implementing ECC prevention is a lack of political prioritisation and funding. Further barriers identified included a lack of integration of public and private preventive programmes, low engagement of professional dental associations, and a lack of population knowledge/awareness of the issue. Implementation might be facilitated through wider universal child health initiatives (e.g. vaccination and maternal health programmes). Conclusion: Mapping disease and oral health prevention activities in Scotland and South-Eastern Europe has allowed for assessment of progress and identified barriers and facilitators for future implementation in line with WHO ECC prevention guidelines

Photosynthesis-dependent H₂O₂ transfer from chloroplasts to nuclei provides a high-light signalling mechanism

Chloroplasts communicate information by signalling to nuclei during acclimation to fluctuating light. Several potential operating signals originating from chloroplasts have been proposed, but none have been shown to move to nuclei to modulate gene expression. One proposed signal is hydrogen peroxide (H2O2) produced by chloroplasts in a light-dependent manner. Using HyPer2, a genetically encoded fluorescent H2O2 sensor, we show that in photosynthetic Nicotiana benthamiana epidermal cells, exposure to high light increases H2O2 production in chloroplast stroma, cytosol and nuclei. Critically, over-expression of stromal ascorbate peroxidase (H2O2 scavenger) or treatment with DCMU (photosynthesis inhibitor) attenuates nuclear H2O2 accumulation and high light-responsive gene expression. Cytosolic ascorbate peroxidase over-expression has little effect on nuclear H2O2 accumulation and high light-responsive gene expression. This is because the H2O2 derives from a sub-population of chloroplasts closely associated with nuclei. Therefore, direct H2O2 transfer from chloroplasts to nuclei, avoiding the cytosol, enables photosynthetic control over gene expression

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Linking Hsp90 function to micro-environmental and stochastic variation in floralorgans of Iris pumila L.

Hsp90 is an environmentally responsive molecular chaperone that was found to play a key role in buffering against genetic and non-genetic perturbations in the model organisms Arabidopsis and Drosophila. Here we analyzed the buffering capacity of Hsp90 against two kinds of non-genetic factors - stochastic noise and micro-environmental varia­tion of floral organ traits in naturally growing Iris pumila plants. We found no statistical association between the endog­enous level of Hsp90 and the floral organ radial symmetry produced by stochastic developmental noise. Conversely, floral organ plasticity in response to micro-environmental variation tended to be greater with decrease in Hsp90b isoform expression

Linking Hsp90 function to micro-environmental and stochastic variation in floralorgans of Iris pumila L.

Hsp90 is an environmentally responsive molecular chaperone that was found to play a key role in buffering against genetic and non-genetic perturbations in the model organisms Arabidopsis and Drosophila. Here we analyzed the buffering capacity of Hsp90 against two kinds of non-genetic factors - stochastic noise and micro-environmental varia­tion of floral organ traits in naturally growing Iris pumila plants. We found no statistical association between the endog­enous level of Hsp90 and the floral organ radial symmetry produced by stochastic developmental noise. Conversely, floral organ plasticity in response to micro-environmental variation tended to be greater with decrease in Hsp90b isoform expression

Linking Hsp90 function to micro-environmental and stochastic variation in floral organs of Iris pumila L.

Abstract — Hsp90 is an environmentally responsive molecular chaperone that was found to play a key role in buffering against genetic and non-genetic perturbations in the model organisms Arabidopsis and Drosophila. Here we analyzed the buffering capacity of Hsp90 against two kinds of non-genetic factors – stochastic noise and micro-environmental variation of floral organ traits in naturally growing Iris pumila plants. We found no statistical association between the endogenous level of Hsp90 and the floral organ radial symmetry produced by stochastic developmental noise. Conversely, floral organ plasticity in response to micro-environmental variation tended to be greater with decrease in Hsp90b isoform expression

Characterisation of antioxidants in photosynthetic and non-photosynthetic leaf tissues of variegated Pelargonium zonale plants

Hydrogen peroxide is an important signalling molecule, involved in regulation of numerous metabolic processes in plants. The most important sources of H2O2 in photosynthetically active cells are chloroplasts and peroxisomes. Here we employed variegated Pelargonium zonale to characterise and compare enzymatic and non-enzymatic components of the antioxidative system in autotrophic and heterotrophic leaf tissues at (sub)cellular level under optimal growth conditions. The results revealed that both leaf tissues had specific strategies to regulate H2O2 levels. In photosynthetic cells, the redox regulatory system was based on ascorbate, and on the activities of thylakoid-bound ascorbate peroxidase (tAPX) and catalase. In this leaf tissue, ascorbate was predominantly localised in the nucleus, peroxisomes, plastids and mitochondria. On the other hand, non-photosynthetic cells contained higher glutathione content, mostly located in mitochondria. The enzymatic antioxidative system in non-photosynthetic cells relied on the ascorbate-glutathione cycle and both Mn and Cu/Zn superoxide dismutase. Interestingly, higher content of ascorbate and glutathione, and higher activities of APX in the cytosol of non-photosynthetic leaf cells compared to the photosynthetic ones, suggest the importance of this compartment in H2O2 regulation. Together, these results imply different regulation of processes linked with H2O2 signalling at subcellular level. Thus, we propose green-white variegated leaves as an excellent system for examination of redox signal transduction and redox communication between two cell types, autotrophic and heterotrophic, within the same organ