Cardiovascular complications after radiotherapy

Over the past decades, effective cancer therapies have resulted in a significant improvement in thesurvival rates for a number of cancers and an increase in the number of cancer survivors. Radiationtherapy is widely used in the treatment of cancer, and it can induce various cardiotoxicities that differconsiderably from chemotherapy-induced cardiotoxicity. They occur primarily as late radiation-inducedcomplications, several years from the end of anticancer treatment and present as coronary artery disease,heart failure, pericardial disease, valvular heart disease and arrhythmias. Patients who recoveredfrom cancer disease suffer from cardiac complications of anticancer treatment, it affects the quality oftheir lives and life expectancy, especially if the diagnosis is delayed. These patients may present distinctsymptoms of cardiac injury, resulting from radiation-induced neurotoxicity and altered pain perception,which makes diagnosis difficult. This review highlights the need for a screening programme for patientswho have undergone radiation therapy and which will subsequently have a potentially profound impacton morbidity and mortality

In vitro interaction network of a synthetic gut bacterial community

A key challenge in microbiome research is to predict the functionality of microbial communities based on community membership and (meta)-genomic data. As central microbiota functions are determined by bacterial community networks, it is important to gain insight into the principles that govern bacteria-bacteria interactions. Here, we focused on the growth and metabolic interactions of the Oligo-Mouse-Microbiota (OMM12) synthetic bacterial community, which is increasingly used as a model system in gut microbiome research. Using a bottom-up approach, we uncovered the directionality of strain-strain interactions in mono- and pairwise co-culture experiments as well as in community batch culture. Metabolic network reconstruction in combination with metabolomics analysis of bacterial culture supernatants provided insights into the metabolic potential and activity of the individual community members. Thereby, we could show that the OMM12 interaction network is shaped by both exploitative and interference competition in vitro in nutrient-rich culture media and demonstrate how community structure can be shifted by changing the nutritional environment. In particular, Enterococcus faecalis KB1 was identified as an important driver of community composition by affecting the abundance of several other consortium members in vitro. As a result, this study gives fundamental insight into key drivers and mechanistic basis of the OMM12 interaction network in vitro, which serves as a knowledge base for future mechanistic in vivo studies

Bi incorporation and segregation in the MBE-grown GaAs-(Ga,Al)As-Ga(As,Bi) core–shell nanowires

Incorporation of Bi into GaAs-(Ga,Al)As-Ga(As,Bi) core–shell nanowires grown by molecular beam epitaxy is studied with transmission electron microscopy. Nanowires are grown on GaAs(111)B substrates with Au-droplet assisted mode. Bi-doped shells are grown at low temperature (300 °C) with a close to stoichiometric Ga/As flux ratio. At low Bi fluxes, the Ga(As,Bi) shells are smooth, with Bi completely incorporated into the shells. Higher Bi fluxes (Bi/As flux ratio ~ 4%) led to partial segregation of Bi as droplets on the nanowires sidewalls, preferentially located at the nanowire segments with wurtzite structure. We demonstrate that such Bi droplets on the sidewalls act as catalysts for the growth of branches perpendicular to the GaAs trunks. Due to the tunability between zinc-blende and wurtzite polytypes by changing the nanowire growth conditions, this effect enables fabrication of branched nanowire architectures with branches generated from selected (wurtzite) nanowire segments

How are "teaching the teachers" courses in evidence based medicine evaluated? A systematic review

Background Teaching of evidence-based medicine (EBM) has become widespread in medical education. Teaching the teachers (TTT) courses address the increased teaching demand and the need to improve effectiveness of EBM teaching. We conducted a systematic review of assessment tools for EBM TTT courses. To summarise and appraise existing assessment methods for teaching the teachers courses in EBM by a systematic review. Methods We searched PubMed, BioMed, EmBase, Cochrane and Eric databases without language restrictions and included articles that assessed its participants. Study selection and data extraction were conducted independently by two reviewers. Results Of 1230 potentially relevant studies, five papers met the selection criteria. There were no specific assessment tools for evaluating effectiveness of EBM TTT courses. Some of the material available might be useful in initiating the development of such an assessment tool. Conclusion There is a need for the development of educationally sound assessment tools for teaching the teachers courses in EBM, without which it would be impossible to ascertain if such courses have the desired effect

Pharmacotherapy of heart failure A.D. 2023. Expert opinion of Working Group on Cardiovascular Pharmacotherapy, Polish Cardiac Society

Heart failure (HF) remains one of the most common causes of hospitalization and mortality among Polish patients. The position of the Section of Cardiovascular Pharmacotherapy presents the currently applicable options for pharmacological treatment of HF based on the latest European and American guidelines from 2021–2022 in relation to Polish healthcare conditions. Treatment of HF varies depending on its clinical presentation (acute/chronic) or left ventricular ejection fraction. Initial treatment of symptomatic patients with features of volume overload is based on diuretics, especially loop drugs. Treatment aimed at reducing mortality and hospitalization should include drugs blocking the renin-angiotensin-aldosterone system, preferably angiotensin receptor antagonist/neprilysin inhibitor, i.e. sacubitril/valsartan, selected beta-blockers (no class effect — options include bisoprolol, metoprolol succinate, or vasodilatory beta-blockers — carvedilol and nebivolol), mineralocorticoid receptor antagonist, and sodium-glucose cotransporter type 2 inhibitor (flozin), constituting the 4 pillars of pharmacotherapy. Their effectiveness has been confirmed in numerous prospective randomized trials. The current HF treatment strategy is based on the fastest possible implementation of all four mentioned classes of drugs due to their independent additive action. It is also important to individualize therapy according to comorbidities, blood pressure, resting heart rate, or the presence of arrhythmias. This article emphasizes the cardio- and nephroprotective role of flozins in HF therapy, regardless of ejection fraction value. We propose practical guidelines for the use of medicines, profile of adverse reactions, drug interactions, as well as pharmacoeconomic aspects. The principles of treatment with ivabradine, digoxin, vericiguat, iron supplementation, or antiplatelet and anticoagulant therapy are also discussed, along with recent novel drugs including omecamtiv mecarbil, tolvaptan, or coenzyme Q10 as well as progress in the prevention and treatment of hyperkalemia. Based on the latest recommendations, treatment regimens for different types of HF are discussed

Integrative inference of gene-regulatory networks in Escherichia coli using information theoretic concepts and sequence analysis

<p>Abstract</p> <p>Background</p> <p>Although <it>Escherichia coli </it>is one of the best studied model organisms, a comprehensive understanding of its gene regulation is not yet achieved. There exist many approaches to reconstruct regulatory interaction networks from gene expression experiments. Mutual information based approaches are most useful for large-scale network inference.</p> <p>Results</p> <p>We used a three-step approach in which we combined gene regulatory network inference based on directed information (DTI) and sequence analysis. DTI values were calculated on a set of gene expression profiles from 19 time course experiments extracted from the Many Microbes Microarray Database. Focusing on influences between pairs of genes in which one partner encodes a transcription factor (TF) we derived a network which contains 878 TF - gene interactions of which 166 are known according to RegulonDB. Afterward, we selected a subset of 109 interactions that could be confirmed by the presence of a phylogenetically conserved binding site of the respective regulator. By this second step, the fraction of known interactions increased from 19% to 60%. In the last step, we checked the 44 of the 109 interactions not yet included in RegulonDB for functional relationships between the regulator and the target and, thus, obtained ten TF - target gene interactions. Five of them concern the regulator LexA and have already been reported in the literature. The remaining five influences describe regulations by Fis (with two novel targets), PhdR, PhoP, and KdgR. For the validation of our approach, one of them, the regulation of lipoate synthase (LipA) by the pyruvate-sensing pyruvate dehydrogenate repressor (PdhR), was experimentally checked and confirmed.</p> <p>Conclusions</p> <p>We predicted a set of five novel TF - target gene interactions in <it>E. coli</it>. One of them, the regulation of <it>lipA </it>by the transcriptional regulator PdhR was validated experimentally. Furthermore, we developed DTInfer, a new R-package for the inference of gene-regulatory networks from microarrays using directed information.</p

Metabolic disorders/obesity is a primary risk factor in hidradenitis suppurativa : an immunohistochemical real-world approach

Background: Hidradenitis suppurativa (HS) is an inflammatory, potentially scarring disease of the hair follicle, affecting the apocrine gland-bearing skin areas. The major comorbid disorders associated with the occurrence or the aggravation of the disease are obesity and smoking. Numerous efforts to dissociate these factors led to controversial results. Objectives: To assess the importance of metabolic disorders/obesity, smoking/environmental toxins, and inflammation in HS by utilizing the differential expression of major relevant protein markers in lesional skin of obese/smoking versus non-obese/non-smoking HS patients. Methods: Lesional skin specimens deriving from two groups of HS patients (BMI &#x3e;30 and smokers, n = 12 vs. BMI &#x3c;30 and non-smokers, n = 10) were stained with antibodies raised against irisin, PPARγ, and IGF-1R, which correlate with metabolic disorders/obesity, EGFR and AhR, associated with smoking, and IL-17, IL-17R, and S100A8, as markers of inflammation. Results: Metabolic disorders/obesity-related markers exhibited marked differential expression between the two groups, while smoking-associated markers a limited one. IL-17R expression was stronger in obese/smokers, and S100A8 staining exhibited intense strong immunoreactivity in both groups without significant difference. Conclusions: The notion that obesity plays a role in HS development appears to be supported by the prominent regulation of the associated lesional biomarkers. Tobacco smoking might contribute less to HS than previously suspected

Comparison of clinical and echocardiographic parameters in patients with hypertrophic cardiomyopathy under and over 60 years of age

Background: Hypertrophic Cardiomyopathy (HCM) is one of the most common genetic myocardial diseases. Transthoracic echocardiography which includes speckle tracking technique is tool for HCM diagnosis and monitoring the course of the disease. The aim of this study was to compare clinical and echocardiographic parameters in HCM patients older and younger than 60 years old (yo). Material and methods: We prospectively enrolled 53 HCM patients, who were divided into two groups: younger and older than 60 yo. Clinical parameters, standard echocardiographic indices, as well as strain parameters were assessed and compared between the groups. Results: The older subgroup was characterized by a higher prevalence of coronary artery disease. In the younger subgroup the incidence of atrial fibrillation was quite high, which occurs far more often than in the general population. Echocardiographic analysis showed worse diastolic function in older, as well as lower volume of the LV. The global longitudinal strain was worse in <60 patients. The 3D strain parameters differed significantly between the groups: the area and radial strains were worse in younger patients. Conclusions: HCM patients older and younger than 60 yo differ significantly in terms of clinical and echocardiographic parameters