The accuracy of Hestia and simplified PESI to predict the prognosis in pulmonary embolism: systematic review with meta-analysis

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)Introduction Pulmonary embolism (PE) patients at low risk of early complications may be considered for early discharge or home treatment. Last decades evidence has been growing about the safety of several clinical prediction rules for selecting those patients, such as simplified Pulmonary Embolism Severity Index (sPESI) and Hestia Criteria. The aim of this review was to compare the safety of both strategies regarding 30-days mortality, venous thromboembolism recurrence and major bleeding. Methods A systematic literature search was conducted using MEDLINE, CENTRAL and Web of Science on 6 th January 2022. We searched for studies that applied both Hestia Criteria and sPESI to the same population. Sensitivity, specificity and diagnostic odds ratio were calculated for both stratification rules. Both Hestia and sPESI criteria of low risk were evaluated to set the number of patients that could be misclassified for each 1000 patients with PE. The estimates were reported with their 95% confidence intervals (95%CI). Results This systematic review included 3 studies. Only mortality data was able to be pooled. Regarding mortality, the sensitivity, specificity and diagnostic odds ratio was 0.923 (95%CI: 0.843-0.964), 0.338 (95%CI: 0.262-0.423) and 6.120 (95%CI: 2.905-12.890) for Hestia Criteria; and 0.972 (95%CI: 0.917-0.991), 0.269 (95%CI: 0.209-0.338) and 12.738 (95%CI: 3.979-40.774) for sPESI score. The negative predictive values were higher than 0.977. The risk of misclassification of high-risk patients in low risk was 5 (95%CI: 3-11) with Hestia and 2 (95%CI: 1-6) with sPESI, for each 1000 patients with PE in terms of mortality. Conclusion The risk of misclassification of patients presenting with low-risk pulmonary embolism with the intent of early discharge or home treatment with both Hestia Criteria and sPESI score is low and these data supports methods for this purpose.info:eu-repo/semantics/publishedVersio

Impact of Chromatin Structures on DNA Processing for Genomic Analyses

Chromatin has an impact on recombination, repair, replication, and evolution of DNA. Here we report that chromatin structure also affects laboratory DNA manipulation in ways that distort the results of chromatin immunoprecipitation (ChIP) experiments. We initially discovered this effect at the Saccharomyces cerevisiae HMR locus, where we found that silenced chromatin was refractory to shearing, relative to euchromatin. Using input samples from ChIP-Seq studies, we detected a similar bias throughout the heterochromatic portions of the yeast genome. We also observed significant chromatin-related effects at telomeres, protein binding sites, and genes, reflected in the variation of input-Seq coverage. Experimental tests of candidate regions showed that chromatin influenced shearing at some loci, and that chromatin could also lead to enriched or depleted DNA levels in prepared samples, independently of shearing effects. Our results suggested that assays relying on immunoprecipitation of chromatin will be biased by intrinsic differences between regions packaged into different chromatin structures - biases which have been largely ignored to date. These results established the pervasiveness of this bias genome-wide, and suggested that this bias can be used to detect differences in chromatin structures across the genome

Silent chromatin at the middle and ends: lessons from yeasts

Eukaryotic centromeres and telomeres are specialized chromosomal regions that share one common characteristic: their underlying DNA sequences are assembled into heritably repressed chromatin. Silent chromatin in budding and fission yeast is composed of fundamentally divergent proteins tat assemble very different chromatin structures. However, the ultimate behaviour of silent chromatin and the pathways that assemble it seem strikingly similar among Saccharomyces cerevisiae (S. cerevisiae), Schizosaccharomyces pombe (S. pombe) and other eukaryotes. Thus, studies in both yeasts have been instrumental in dissecting the mechanisms that establish and maintain silent chromatin in eukaryotes, contributing substantially to our understanding of epigenetic processes. In this review, we discuss current models for the generation of heterochromatic domains at centromeres and telomeres in the two yeast species

Histone H4 Lysine 12 Acetylation Regulates Telomeric Heterochromatin Plasticity in Saccharomyces cerevisiae

Recent studies have established that the highly condensed and transcriptionally silent heterochromatic domains in budding yeast are virtually dynamic structures. The underlying mechanisms for heterochromatin dynamics, however, remain obscure. In this study, we show that histones are dynamically acetylated on H4K12 at telomeric heterochromatin, and this acetylation regulates several of the dynamic telomere properties. Using a de novo heterochromatin formation assay, we surprisingly found that acetylated H4K12 survived the formation of telomeric heterochromatin. Consistently, the histone acetyltransferase complex NuA4 bound to silenced telomeric regions and acetylated H4K12. H4K12 acetylation prevented the over-accumulation of Sir proteins at telomeric heterochromatin and elimination of this acetylation caused defects in multiple telomere-related processes, including transcription, telomere replication, and recombination. Together, these data shed light on a potential histone acetylation mark within telomeric heterochromatin that contributes to telomere plasticity

Physical Analyses of E. coli Heteroduplex Recombination Products In Vivo: On the Prevalence of 5′ and 3′ Patches

BACKGROUND: Homologous recombination in Escherichia coli creates patches (non-crossovers) or splices (half crossovers), each of which may have associated heteroduplex DNA. Heteroduplex patches have recombinant DNA in one strand of the duplex, with parental flanking markers. Which DNA strand is exchanged in heteroduplex patches reflects the molecular mechanism of recombination. Several models for the mechanism of E. coli RecBCD-mediated recombinational double-strand-end (DSE) repair specify that only the 3'-ending strand invades the homologous DNA, forming heteroduplex in that strand. There is, however, in vivo evidence that patches are found in both strands. METHODOLOGY/PRINCIPLE FINDINGS: This paper re-examines heteroduplex-patch-strand polarity using phage lambda and the lambdadv plasmid as DNA substrates recombined via the E. coli RecBCD system in vivo. These DNAs are mutant for lambda recombination functions, including orf and rap, which were functional in previous studies. Heteroduplexes are isolated, separated on polyacrylamide gels, and quantified using Southern blots for heteroduplex analysis. This method reveals that heteroduplexes are still found in either 5' or 3' DNA strands in approximately equal amounts, even in the absence of orf and rap. Also observed is an independence of the RuvC Holliday-junction endonuclease on patch formation, and a slight but statistically significant alteration of patch polarity by recD mutation. CONCLUSIONS/SIGNIFICANCE: These results indicate that orf and rap did not contribute to the presence of patches, and imply that patches occurring in both DNA strands reflects the molecular mechanism of recombination in E. coli. Most importantly, the lack of a requirement for RuvC implies that endonucleolytic resolution of Holliday junctions is not necessary for heteroduplex-patch formation, contrary to predictions of all of the major previous models. This implies that patches are not an alternative resolution of the same intermediate that produces splices, and do not bear on models for splice formation. We consider two mechanisms that use DNA replication instead of endonucleolytic resolution for formation of heteroduplex patches in either DNA strand: synthesis-dependent-strand annealing and a strand-assimilation mechanism

Linking Indigenous Peoples’ Health-Related Decision Making to Information Communication Technology: Insights from an Emerging Economy

Indigenous peoples are being marginalised globally from a socioeconomic perspective and are often excluded from mainstream communities for social and/or geographic reasons. Historically, they tend to have lower living standards, including poor health conditions as compared to the rest of the population. Literature suggests that information and communication technologies (ICTs) have the potential to improve awareness about how to improve health and wellbeing. In order to both deepen and broaden the understanding of how ICTs can influence Indigenous peoples’ health-related decision-making, this study has developed a conceptual framework based on the capability approach, focusing on the five dimensions of freedoms suggested by Amartya Sen. Data collected from a sample of members of an Indigenous community in Bangladesh, using a purposive sampling method, were analysed through qualitative techniques to identify ways in which a mobile-based health system have influenced the lives of indigenous people. The findings revealed that the mobile healthcare system explored in this study addressed a number of factors pertaining to indigenous peoples’ quality of life. These findings are useful for policy formulation related to the design and implementation of healthcare strategies in Bangladesh. The conceptual framework, following further validation, could serve as a platform for the advancement of research towards understanding how mobile healthcare systems can improve the wellbeing of individuals in indigenous communities