Use of cangrelor in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Study design and interim analysis of the ARCANGELO study

BackgroundThe itAlian pRospective Study on CANGrELOr (ARCANGELO) was aimed to assess the safety of using cangrelor during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) in the daily practice.HypothesisThe safety of cangrelor after the transition to oral P2Y12 inhibitors was evaluated as the incidence of bleeding outcomes in the 30 days following PCI according to postauthorization safety study guidelines.MethodsAdults with ACS who were treated with cangrelor in one of the 28 centers involved in the study. Patients who consented to participate were followed in the 30 days following their PCI. Bleedings (Bleeding Academic Research Consortium [BARC] classification), major adverse cardiac events (MACEs), and adverse events were recorded. The interim results at two‐thirds of the enrollment period are presented.ResultsA total of 17 bleedings were observed in the 320 patients who completed the study at this stage. All bleedings were classified as BARC Type 1–2, except for one case of Type 3a (vessel puncture site hematoma). Four patients experienced MACEs (2 acute myocardial infarctions, 1 sudden cardiac death, 1 noncardiovascular death due to respiratory distress, and multiorgan failure). None of the bleedings was rated as related to cangrelor.ConclusionsThe interim results of the ARCANGELO study provide a preliminary confirmation that the use of cangrelor on patients with ACS undergoing PCI is not associated with severe bleedings.     

Development of a Portland Cement-Based Material with Agave salmiana Leaves Bioaggregate

Depending on the morphology of the natural fibers, they can be used as reinforcement to improve flexural strength in cement-based composites or as aggregates to improve thermal conductivity properties. In this last aspect, hemp, coconut, flax, sunflower, and corn fibers have been used extensively, and further study is expected into different bioaggregates that allow diversifying of the raw materials. The objective of the research was to develop plant-based concretes with a matrix based on Portland cement and an aggregate of Agave salmiana (AS) leaves, obtained from the residues of the tequila industry that have no current purpose, as a total replacement for the calcareous aggregates commonly used in the manufacturing of mortars and whose extraction is associated with high levels of pollution, to improve their thermal properties and reduce the energy demand for air conditioning in homes. Characterization tests were carried out on the raw materials and the vegetal aggregate was processed to improve its compatibility with the cement paste through four different treatments: (a) freezing (T/C), (b) hornification (T/H), (c) sodium hydroxide (T/NaOH), and (d) solid paraffin (T/P). The effect of the treatments on the physical properties of the resulting composite was evaluated by studying the vegetal concrete under thermal conductivity, bulk density, and compressive strength tests with a volumetric ratio between the vegetal aggregate and the cement paste of 0.36 and a water/cement ratio of 0.35. The hornification treatment showed a 15.2% decrease in the water absorption capacity of the aggregate, resulting in a composite with a thermal conductivity of 0.49 W/mK and a compressive strength of 8.66 MPa, which allows its utilization as a construction material to produce prefabricated blocks.     

Patient-Factors Influencing the 2-Year Trajectory of Mental and Physical Health in Prostate Cancer Patients

This study aimed to examine the physical and mental Quality of Life (QoL) trajectories in prostate cancer (PCa) patients participating in the Pros-IT CNR study. QoL was assessed using the Physical (PCS) and Mental Component Score (MCS) of Short-Form Health Survey upon diagnosis and two years later. Growth mixture models were applied on 1158 patients and 3 trajectories over time were identified for MCS: 75% of patients had constantly high scores, 13% had permanently low scores and 12% starting with low scores had a recovery; the predictors that differentiated the trajectories were age, comorbidities, a family history of PCa, and the bowel, urinary and sexual functional scores at diagnosis. In the physical domain, 2 trajectories were defined: 85% of patients had constantly high scores, while 15% started with low scores and had a further slight decrease. Two years after diagnosis, the psychological and physical status was moderately compromised in more than 10% of PCa patients. For mental health, the trajectory analysis suggested that following the compromised patients at diagnosis until treatment could allow identification of those more vulnerable, for which a level 2 intervention with support from a non-oncology team supervised by a clinical psychologist could be of help.     

In vitro activity of Tridax procumbens against promastigotes of Leishmania mexicana

Ethnopharmacological relevance

Tridax procumbens is an active herb against leishmaniasis.

Aim of the study

Leishmaniasis is a group of diseases caused by Leishmania protozoa. We investigated the antileishmanial activity of Tridax procumbens extracts and a pure compound against promastigotes of Leishmania mexicana, the causative agent of cutaneous leishmaniasis in the New World.

Materials and methods

Extracts and (3S)-16,17-didehydrofalcarinol (1) were obtained by chromatographic methods from Tridax procumbens, and the latter identified by spectroscopic analysis. The effect of these extracts and 1 on the growth inhibition of promastigotes of Leishmania mexicana was evaluated. In order to test the safety of extracts and 1, mammalian cells were treated with them, and cell viability was assessed using trypan blue and MTT.

Results

We demonstrated that extracts of Tridax procumbens and 1 showed a pronounced activity against Leishmania mexicana. The methanol extract inhibited promastigotes growth of Leishmania mexicana with a 50% inhibitory concentration (IC₅₀) of 3 μg/ml, while oxylipin 1 exhibited the highest inhibition at IC₅₀ = 0.478 μg/ml.

Conclusions

In this study we report the biological activity of extracts and (3S)-16,17-didehydrofalcarinol (1), obtained from Tridax procumbens, on the promastigote form of Leishmania mexicana, with no effect upon mammalian cells.     

O Uso da Escala de Borg na Percepção do Esforço em Manobras de Reanimação Cardiopulmonar

BackgroundA cardiopulmonary arrest is a critical event whose survival rate is related to the quality of resuscitation maneuvers combined with the use of technology. It is important to understand the perception of fatigue during this procedure, aiming to improve the effectiveness of compressions to increase the chances of survival.ObjectivesTo apply the Borg rating of perceived exertion scale (Borg scale) to analyze the exertion perceived by nurses during cardiopulmonary resuscitation maneuvers using a feedback device.MethodsExperimental study with a randomized distribution of nurses in a teaching hospital. Perceived exertion during simulated cardiopulmonary resuscitation with/without a feedback device was assessed using the Borg scale. The statistical significance level of 5% was adopted.Results69 nurses working in critical and non-critical adult care units were included. Perceived exertion and heart rate were lower in the intervention group (p<0.001), influenced by the feedback device, with no significant difference between critical and non-critical units.ConclusionsThe Borg scale proved to be adequate for the proposed objectives. The feedback device contributed to lower exertion and heart rate reduction during resuscitation maneuvers. The low cost and ease of application favor its use during training and real-time resuscitation attempts to assess performance using a feedback device to reduce exertion and perception of fatigue. It allows reflection on the intervening factors and resources that can influence the quality of resuscitation attempts and the chances of survival.     

Robust analysis of prokaryotic pangenome gene gain and loss rates with Panstripe

Horizontal gene transfer (HGT) plays a critical role in the evolution and diversification of many microbial species. The resulting dynamics of gene gain and loss can have important implications for the development of antibiotic resistance and the design of vaccine and drug interventions. Methods for the analysis of gene presence/absence patterns typically do not account for errors introduced in the automated annotation and clustering of gene sequences. In particular, methods adapted from ecological studies, including the pangenome gene accumulation curve, can be misleading as they may reflect the underlying diversity in the temporal sampling of genomes rather than a difference in the dynamics of HGT. Here, we introduce Panstripe, a method based on generalized linear regression that is robust to population structure, sampling bias, and errors in the predicted presence/absence of genes. We show using simulations that Panstripe can effectively identify differences in the rate and number of genes involved in HGT events, and illustrate its capability by analyzing several diverse bacterial genome data sets representing major human pathogens.

Genetic variation within microbial populations is shaped by both the accumulation of variation from point mutations as well as by the acquisition and loss of genetic material through horizontal gene transfer (HGT). HGT can occur via the uptake of DNA from the environment, with the help of mobile genetic elements (MGEs; phages, integrative conjugative elements, and plasmids), or from direct contact between bacterial cells (Thomas and Nielsen 2005). Genes are also frequently duplicated and lost vertically upon cell division (Arnold et al. 2022). The influence of these sources of variation varies by species. Clonal species such as Mycobacterium tuberculosis (Mtb) typically accumulate variation nearly entirely through point mutations, whereas naturally transformable species such as Streptococcus pneumoniae and Neisseria meningitidis have very high rates of homologous recombination (Dubnau 1999). In other species such as Salmonella enterica, horizontal exchange is generally restricted to the movement of MGEs (Harris et al. 2010). Although HGT does not always have an impact on a microbe''s fitness, it can lead to critical phenotypic changes such as the acquisition of antimicrobial resistance, virulence factors, and vaccine escape (Croucher et al. 2013; Wyres et al. 2019).A common approach to analyzing horizontal exchange in microbial genomics is to group homologous gene sequences into orthologous and paralogous gene clusters. The union of these clusters within a particular species or group is commonly referred to as the pangenome (Medini et al. 2005). Genes are often further classified into either the “core” genome, which is found in almost all members of the group, or the “accessory” genome, which is only found in a subset of genomes. Species with a limited accessory genome such that all genes are likely to have already been observed are often described as “closed,” whereas species with a diverse accessory genome are described as “open.”A number of tools have been developed to infer a pangenome given a collection of annotated genomes (Page et al. 2015; Ding et al. 2018; Bayliss et al. 2019; Gautreau et al. 2020; Tonkin-Hill et al. 2020; Zhou et al. 2020). A common output of these algorithms is a binary gene presence/absence matrix where genomes are represented by rows and orthologous gene clusters by columns. After generating a gene presence/absence matrix, researchers are often interested in comparing the size of pangenomes between data sets, determining the rate of horizontal gene exchange as well as identifying whether a pangenome is “open” or “closed.”A gene accumulation curve, as is often performed in ecological studies of species diversity, is often used to investigate these questions (Ugland et al. 2003; Medini et al. 2005). Here, the number of unique gene clusters identified is plotted against the number of genomes. Random permutations are often used to account for the variation caused by the order in which genomes are considered in the plot. In some cases, a power law such as Heaps’ or Zipf''s law is fit to this curve to give a parameter estimate of the diminishing number of new genes found with each additional genome and to determine whether the pangenome is open or closed (Tettelin et al. 2008).A neglected problem with this approach is that it fails to account for the underlying diversity of the set of sampled genomes. For example, a set of genomes taken from within an outbreak is likely to involve far fewer gene exchange events than a diverse sample from a species with thousands of years of evolution separating isolates. Methods that make use of a phylogeny constructed from the genetic diversity present in genes found in all the genomes (the “core” genome) help to address this issue by controlling for the underlying diversity of the sample. The branch lengths of the core genome phylogeny indicate the evolutionary time over which gene gain and loss events could have occurred. Shorter branch lengths separating more closely related taxa would be expected to have fewer associated gene exchange events. Methods that rely on the construction of such a phylogeny include those based on maximum parsimony (Mirkin et al. 2003), maximum likelihood (Hao and Golding 2006; Cohen and Pupko 2010; Han et al. 2013), and Bayesian phylogenetics (Liu et al. 2011). Two notable models that use this approach are the infinitely many genes (IMG) model and the finitely many genes (FMG) model (Baumdicker et al. 2010, 2012; Collins and Higgs 2012; Zamani-Dahaj et al. 2016). The IMG model assumes an infinite pool of genes and that a particular gene can only be gained once, whereas the FMG model assumes that genes belong to a finite pool and that multiple gene gain and loss events of the same gene can occur. Many models also collapse paralogous clusters into gene families before the inference of gene gain and loss rates (Mirkin et al. 2003; Cohen and Pupko 2010; Han et al. 2013).A significant limitation of these approaches is that they generally assume that there is no error in the inferred pangenome presence/absence matrix. We and others have shown that gene annotation errors and the complexities of clustering genes into orthologous families can introduce substantial numbers of erroneous gene clusters (Han et al. 2013; Salzberg 2019; Tonkin-Hill et al. 2020; Zhou et al. 2020). Although a subset of models do account for errors in the predicted presence/absence of genes, these have mostly been optimized for the analysis of eukaryotes and focus on a small number of gene families involving multiple genes (Han et al. 2013). Most models also make the simplifying assumption that genes are gained or lost individually, which can significantly bias estimates of the rate of gene exchange, particularly when the exchange of MGEs is frequent (Baumdicker et al. 2012; Zamani-Dahaj et al. 2016).To address these limitations, we have developed Panstripe, an approach that compares the rates of core and accessory genome evolution to account for both population structure and errors in the pangenome gene presence/absence matrix. Using extensive simulations and by analyzing a diverse range of bacterial genome data sets, we show that Panstripe can effectively identify the rate of gene exchange in pangenomes, detect the presence of a temporal signal in the accessory genome, and discern whether the size of gene exchange events varies between pangenomes.