Empagliflozin in Heart Failure With Predicted Preserved Versus Reduced Ejection Fraction: Data From the EMPA-REG OUTCOME Trial

Background: In the EMPA-REG OUTCOME trial, ejection fraction (EF) data were not collected. In the subpopulation with heart failure (HF), we applied a new predictive model for EF to determine the effects of empagliflozin in HF with predicted reduced (HFrEF) vs preserved (HFpEF) EF vs no HF. / Methods and Results: We applied a validated EF predictive model based on patient baseline characteristics and treatments to categorize patients with HF as being likely to have HF with mid-range EF (HFmrEF)/HFrEF (EF <50%) or HFpEF (EF ≥50%). Cox regression was used to assess the effect of empagliflozin vs placebo on cardiovascular death/HF hospitalization (HHF), cardiovascular and all-cause mortality, and HHF in patients with predicted HFpEF, HFmrEF/HFrEF and no HF. Of 7001 EMPA-REG OUTCOME patients with data available for this analysis, 6314 (90%) had no history of HF. Of the 687 with history of HF, 479 (69.7%) were predicted to have HFmrEF/HFrEF and 208 (30.3%) to have HFpEF. Empagliflozin's treatment effect was consistent in predicted HFpEF, HFmrEF/HFrEF and no-HF for each outcome (HR [95% CI] for the primary outcome 0.60 [0.31–1.17], 0.79 [0.51–1.23], and 0.63 [0.50–0.78], respectively; P interaction = 0.62). / Conclusions: In EMPA-REG OUTCOME, one-third of the patients with HF had predicted HFpEF. The benefits of empagliflozin on HF and mortality outcomes were consistent in nonHF, predicted HFpEF and HFmrEF/HFrEF

Comparison of four different treatment strategies in teeth with molar-incisor hypomineralization-related enamel breakdown–A retrospective cohort study

Background There is little information available on the longevity of non-invasive glass ionomer cement (GIC) and composite restorations as well as conventional composite and ceramic restorations placed on permanent teeth with enamel breakdowns due to molar-incisor hypomineralization (MIH). Aim To compare the longevity of the abovementioned treatment procedures. Design Of 377 identified MIH patients, 118 individuals received restorative treatment and were invited for clinical examination, including caries and MIH status. Finally, survival data from 204 MIH-related restorations placed on 127 teeth were retrospectively collected from 52 children, monitored between 2010 and 2018. Descriptive and explorative analyses were performed, including Kaplan-Meier estimators and the Cox regression model. Results The mean patient observation time was 42.9 months (SD = 35.1). The cumulative survival probabilities after 36 months—7.0% (GIC, N = 28), 29.9% (non-invasive composite restoration, N = 126), 76.2% (conventional composite restoration, N = 27) and 100.0% (ceramic restoration, N = 23)—differed significantly in the regression analysis. Conclusions Conventional restorations were associated with moderate-to-high survival rates in MIH teeth. In contrast, non-invasive composite restorations, which were predominately used in younger or less cooperative children, were linked to lower survival rates

Mass Spectrometric Analyses of Organophosphate Insecticide Oxon Protein Adducts

OBJECTIVE: Organophosphate (OP) insecticides continue to be used to control insect pests. Acute and chronic exposures to OP insecticides have been documented-to cause adverse health effects, but few OP-adducted proteins have been correlated with these illnesses at the molecular level. Our aim was to review the literature covering the current state of the art in mass spectrometry (MS) used to identify OP protein biomarkers. DATA SOURCES AND EXTRACTION: We identified general and specific research reports related to OP insecticides, OP toxicity, OP structure, and protein MS by searching PubMed and Chemical Abstracts for articles published before December 2008. DATA SYNTHESIS: A number of OP-based insecticides share common structural elements that result in predictable OP-protein adducts. The resultant OP-protein adducts show an increase in molecular mass that can be identified by MS and correlated with the OP agent. Customized OP-containing probes have also been used to tag and identify protein targets that can be identified by MS. CONCLUSIONS: MS is a useful and emerging tool for the identification of proteins that are modified by activated organophosphate insecticides. MS can characterize the structure of the OP adduct and also the specific amino acid residue that forms the key bond with the OP. Each protein that is modified in a unique way by an OP represents a unique molecular biomarker that with further research can lead to new correlations with exposure

Benchmarking of cell type deconvolution pipelines for transcriptomics data

Many computational methods have been developed to infer cell type proportions from bulk transcriptomics data. However, an evaluation of the impact of data transformation, pre-processing, marker selection, cell type composition and choice of methodology on the deconvolution results is still lacking. Using five single-cell RNA-sequencing (scRNA-seq) datasets, we generate pseudo-bulk mixtures to evaluate the combined impact of these factors. Both bulk deconvolution methodologies and those that use scRNA-seq data as reference perform best when applied to data in linear scale and the choice of normalization has a dramatic impact on some, but not all methods. Overall, methods that use scRNA-seq data have comparable performance to the best performing bulk methods whereas semi-supervised approaches show higher error values. Moreover, failure to include cell types in the reference that are present in a mixture leads to substantially worse results, regardless of the previous choices. Altogether, we evaluate the combined impact of factors affecting the deconvolution task across different datasets and propose general guidelines to maximize its performance. Inferring cell type proportions from transcriptomics data is affected by data transformation, normalization, choice of method and the markers used. Here, the authors use single-cell RNAseq datasets to evaluate the impact of these factors and propose guidelines to maximise deconvolution performance

A concept for integrated care pathways for atopic dermatitis-A GA2 LEN ADCARE initiative

INTRODUCTION: The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. METHODS: The GA2 LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2 EN ADCARE centres. RESULTS: The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. CONCLUSION: The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD

Deterministic Chaos and Fractal Complexity in the Dynamics of Cardiovascular Behavior: Perspectives on a New Frontier

Physiological systems such as the cardiovascular system are capable of five kinds of behavior: equilibrium, periodicity, quasi-periodicity, deterministic chaos and random behavior. Systems adopt one or more these behaviors depending on the function they have evolved to perform. The emerging mathematical concepts of fractal mathematics and chaos theory are extending our ability to study physiological behavior. Fractal geometry is observed in the physical structure of pathways, networks and macroscopic structures such the vasculature and the His-Purkinje network of the heart. Fractal structure is also observed in processes in time, such as heart rate variability. Chaos theory describes the underlying dynamics of the system, and chaotic behavior is also observed at many levels, from effector molecules in the cell to heart function and blood pressure. This review discusses the role of fractal structure and chaos in the cardiovascular system at the level of the heart and blood vessels, and at the cellular level. Key functional consequences of these phenomena are highlighted, and a perspective provided on the possible evolutionary origins of chaotic behavior and fractal structure. The discussion is non-mathematical with an emphasis on the key underlying concepts