Despite recent advances in the treatment of some forms of leishmaniasis, the available drugs are still far from ideal due to inefficacy, parasite resistance, toxicity and cost. The wide-spectrum ...antimicrobial activity of 2-nitrovinylfuran compounds has been described, as has their activity against Trichomonas vaginalis and other protozoa. Thus, the aim of this study was to test the antileishmanial activities of six 2-nitrovinylfurans in vitro and in a murine model of leishmaniasis. Minimum parasiticide concentration (MPC) and 50% inhibitory concentration (IC50) values for these compounds against the promastigotes of Leishmania amazonensis, Leishmania infantum and Leishmania braziliensis were determined, as were the efficacies of two selected compounds in an experimental model of cutaneous leishmaniasis (CL) caused by L. amazonensis in BALB/c mice. All of the compounds were active against the promastigotes of the three Leishmania species tested. IC50 and MPC values were in the ranges of 0.8-4.7 µM and 1.7-32 µM, respectively. The compounds 2-bromo-5-(2-bromo-2-nitrovinyl)-furan (furvina) and 2-bromo-5-(2-methyl-2-nitrovinyl)-furan (UC245) also reduced lesion growth in vivo at a magnitude comparable to or higher than that achieved by amphotericin B treatment. The results demonstrate the potential of this class of compounds as antileishmanial agents and support the clinical testing of Dermofural(r) (a furvina-containing antifungal ointment) for the treatment of CL.
In the 20th century, research focused on cholesterol and lipoproteins as the key mechanism in establishing atherosclerotic cardiovascular disease (ASCVD). Given that some studies demonstrated ...subclinical atherosclerosis in subjects without conventional cardiovascular risk factors, the elevated low-density lipoprotein (LDL) levels alone cannot account for the entire burden of atherosclerosis. Hence, large-scale clinical trials demonstrated the operation of immune and inflammatory pathways in ASCVD. In this regard, the evidence establishes that cells of the immune system, both the innate (neutrophils, macrophages) and adaptive (T cell and other lymphocytes) limbs, contribute to atherosclerosis and atherothrombosis. Besides, basic science studies have identified proatherogenic cytokines such as interleukin (IL)-1, IL-12, and IL-18. In this regard, some studies showed that antiinflammatory therapy targeting the immune system by modulating or blocking interleukins, also known as anti-cytokine therapy, can reduce the risk of major cardiovascular adverse events. The neutrophils play a key role in the innate immune system, representing the acute phase of an inflammatory response. In contrast, lymphocytes represent the adaptive immune system and promote the induction of autoimmune inflammation, especially in the chronic inflammatory response. Through the literature review, we will highlight the inflammatory pathway for the physiopathology of ASCVD, HF, and COVID-19. In this regard, the neutrophil-to-lymphocyte ratio (NLR) integrates the innate immune and adaptive immune systems, making the NLR a biomarker of inflammation. In addition, we provided an update on the evidence showing that high NLR is associated with worse prognosis in heart failure (HF), ASCVD, and COVID-19, as well as their clinical applications showing that the normalization of NLR after anti-cytokine therapy is a potential predictor of therapy responsiveness and is associated with reduction of major adverse cardiovascular events.
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•Current evidence supports the operation of the immune system and inflammatory pathways in atherosclerotic disease.•High neutrophil-lymphocyte ratio (NLR) is associated with a greater inflammatory response and is a prognostic marker.•Antiinflammatory therapy targeting the immune reduces cardiovascular events in patients with atherosclerotic disease.•A high NLR is a potential marker to select the appropriate candidates that may benefit from anti-cytokine therapy.•Normal NLR after anti-cytokine therapy is a predictor of therapy responsiveness in atherosclerotic and inflammatory diseases.
Bone tissue has the capacity to regenerate under healthy conditions, but complex cases like critically sized defects hinder natural bone regeneration, necessitating surgery, and use of a grafting ...material for rehabilitation. The field of bone tissue engineering (BTE) has pioneered ways to address such issues utilizing different biomaterials to create a platform for cell migration and tissue formation, leading to improved bone reconstruction. One such approach involves 3D‐printed patient‐specific scaffolds designed to aid in regeneration of boney defects. This study aimed to develop and characterize 3D printed scaffolds composed of type I collagen augmented with β‐tricalcium phosphate (COL/β‐TCP). A custom‐built direct inkjet write (DIW) printer was used to fabricate β‐TCP, COL, and COL/β‐TCP scaffolds using synthesized colloidal gels. After chemical crosslinking, the scaffolds were lyophilized and subjected to several characterization techniques, including light microscopy, scanning electron microscopy, and x‐ray diffraction to evaluate morphological and chemical properties. In vitro evaluation was performed using human osteoprogenitor cells to assess cytotoxicity and proliferative capacity of the different scaffold types. Characterization results confirmed the presence of β‐TCP in the 3D printed COL/β‐TCP scaffolds, which exhibited crystals that were attributed to β‐TCP due to the presence of calcium and phosphorus, detected through energy dispersive x‐ray spectroscopy. In vitro studies showed that the COL/β‐TCP scaffolds yielded more favorable results in terms of cell viability and proliferation compared to β‐TCP and COL scaffolds. The novel COL/β‐TCP scaffold constructs hold promise for improving BTE applications and may offer a superior environment for bone regeneration compared with conventional COL and β‐TCP scaffolds.
The establishment of radiofrequency catheter ablation techniques as the mainstay in the treatment of tachycardia has renewed new interest in cardiac anatomy. The interventional arrhythmologist has ...drawn attention not only to the gross anatomic details of the heart but also to architectural and histological characteristics of various cardiac regions that are relevant to the development or recurrence of tachyarrhythmias and procedural related complications of catheter ablation. In this review, therefore, we discuss some anatomic landmarks commonly used in catheter ablations including the terminal crest, sinus node region, Koch’s triangle, cavotricuspid isthmus, Eustachian ridge and valve, pulmonary venous orifices, venoatrial junctions, and ventricular outflow tracts. We also discuss the anatomical features of important structures in the vicinity of the atria and pulmonary veins, such as the esophagus and phrenic nerves. This paper provides basic anatomic information to improve understanding of the mapping and ablative procedures for cardiac interventional electrophysiologists.
Data scientists require rich mental models of how AI systems behave to effectively train, debug, and work with them. Despite the prevalence of AI analysis tools, there is no general theory describing ...how people make sense of what their models have learned. We frame this process as a form of sensemaking and derive a framework describing how data scientists develop mental models of AI behavior. To evaluate the framework, we show how existing AI analysis tools fit into this sensemaking process and use it to design AIFinnity, a system for analyzing image-and-text models. Lastly, we explored how data scientists use a tool developed with the framework through a think-aloud study with 10 data scientists tasked with using AIFinnity to pick an image captioning model. We found that AIFinnity’s sensemaking workflow reflected participants’ mental processes and enabled them to discover and validate diverse AI behaviors.
This study sought to describe, in detail, the angiographic, gross macroscopy, and histological dissection of the conduction axis in humans.
The recent upsurge of interest in specific pacing of the ...atrioventricular conduction axis has emphasized the need for precise knowledge of the location of the atrial and penetrating components of the atrioventricular conduction axis.
A total of 41 human hearts were studied by serial histological sectioning and an additional 3 hearts by gross dissection. One of the hearts studied histologically was also dissected to show the location of the conduction axis prior to serial sectioning. The anatomical findings were then compared with the results of angiography undertaken in the catheter laboratory in 60 patients undergoing electrophysiological studies.
Marked variation of the location of the transition from atrioventricular conduction axis to the penetrating atrioventricular bundle, or the bundle of His, relative to the landmarks of the triangle of Koch was observed. In just over one-half of both the specimens and the patients, the site of penetration was on the atrial aspect of the hinge of the septal leaflet of the tricuspid valve, with further variation noted relative to the apex of the triangle of Koch. Based on measurements of the histological sections, marked variation in the dimensions of the axis and its adjacency to the right-sided endocardium were also found. In almost three-fifths of hearts, an interventricular component of the fibrous membranous septum was not able to be identified. The significance of these findings to those who seek to perform selective pacing of the atrioventricular conduction axis are discussed.
Marked variability of the location of the conduction axis within the triangle of Koch is reported. In three-fifths of hearts, the interventricular component of the fibrous membranous septum is nonexistent.
Chemical carcinogenicity is of primary interest, because it drives much of the current regulatory actions regarding new and existing chemicals. This paper reports a QSAR study for predicting ...carcinogenic potency of nitrocompounds. Several different theoretical molecular descriptors, calculated only on the basis of knowledge of the molecular structure and an efficient variable selection procedure led to models with satisfactory predictive ability.
Chemical carcinogenicity is of primary interest, because it drives much of the current regulatory actions regarding new and existing chemicals, and its conventional experimental test takes around three years to design, conduct, and interpret as well as the costs of hundreds of millions of dollars, millions of skilled personnel hours, and several animal lives. Both academia and private companies are actively trying to develop alternative methods, such as QSAR models. This paper reports a QSAR study for predicting carcinogenic potency of nitrocompounds bioassayed in female rats. Several different theoretical molecular descriptors, calculated only on the basis of knowledge of the molecular structure and an efficient variable selection procedure, such as Genetic Algorithm, led to models with satisfactory predictive ability. But the best-final QSAR model is based on the GEometry, Topology, and Atom-Weights AssemblY (GETAWAY) descriptors capturing a reasonable interpretation. In fact, structural features such as molecular shape—linear, branched, cyclic, and polycyclic—and bond length are some of the key factors flagging the carcinogenicity of this set of nitrocompounds. This QSAR model, after removal of one identified nitrocompound outlier, is able to explain around 86% of the variance in the experimental activity and manifest good predictive ability as indicated by the higher
q
2s of cross- and external-validations, which demonstrate the practical value of the final QSAR model for screening and priority testing. This model can be applied to nitrochemicals different from the studied nitrocompounds (even those not yet synthesized) as it is based on theoretical molecular descriptors that might be easily and rapidly calculated.
The attractiveness of airlines is a topic of great interest to researchers and professionals wishing to understand the ability of airlines to attract and satisfy air passengers. However, there is a ...lack of consensus on which attributes of the airline are important for attracting and satisfying passengers. In general, previous studies have mostly focused on a limited number of attributes affecting a passenger's choice of airline, satisfaction, behaviour and loyalty. This study aims to develop a model to measure the importance of airline attributes, a model which could be adopted by future research on airline attractiveness. Besides a review of previous empirical research on the topic, an empirical study was conducted among air passengers at a major international airport in Spain. Results revealed the existence of eight categories of attributes that are important for airline passengers. The most important categories were: ‘safety and punctuality’, ‘ticket price’, and ‘attention and service during the customer journey’. In addition, air travel frequency and socio-demographic characteristics affected the perceived importance of the categories of attributes. For instance, air travel frequency had a positive influence on the importance passengers attach to ‘safety and punctuality’, ‘flight schedule and connections’, and ‘in-flight space’.
•Eight categories of important airline attributes that are important for passengers when selecting and evaluating an airline.•A validated scale to measure the attractiveness of airlines.•Socio-demographic characteristics, except age, affected the importance passengers attached to airline attributes.•Air travel frequency affected the perceived importance of categories of attributes.
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