Breast Cancer Plasticity after Chemotherapy Highlights the Need for Re-Evaluation of Subtyping in Residual Cancer and Metastatic Tissues.

This research paper presents a novel approach to identifying biomarkers that can be used to prognosticate patients with triple-negative breast cancer (TNBC) eligible for neoadjuvant therapy. The study utilized survival and RNA sequencing data from a cohort of TNBC patients and identified 276 genes whose expression was related to survival in such patients. The gene expression data were then used to classify patients into two major groups based on the presence or absence of Wingless/Integrated-pathway (Wnt-pathway) and mesenchymal (Mes) markers (Wnt/Mes). Patients with a low expression of Wnt/Mes-related genes had a favorable outcome, with no deaths observed during follow-up, while patients with a high expression of Wnt/Mes genes had a higher mortality rate of 50% within 19 months. The identified gene list could be validated and potentially used to shape treatment options for TNBC patients eligible for neoadjuvant therapy providing valuable insights into the development of more effective treatments for TNBC. Our data also showed significant variation in gene expression profiles before and after chemotherapy, with most tumors switching to a more mesenchymal/stem cell-like profile. To verify this observation, we performed an in silico analysis to classify breast cancer tumors in Prediction Analysis of Microarray 50 (PAM50) molecular classes before treatment and after treatment using gene expression data. Our findings demonstrate that following drug intervention and metastasis, certain tumors undergo a transition to alternative subtypes, resulting in diminished therapeutic efficacy. This underscores the necessity for reevaluation of patients who have experienced relapse or metastasis post-chemotherapy, with a focus on molecular subtyping. Tailoring treatment strategies based on these refined subtypes is imperative to optimize therapeutic outcomes for affected individuals.

The Fetal Alcohol Spectrum Disorders-An Overview of Experimental Models, Therapeutic Strategies, and Future Research Directions.

Since the establishment of a clear link between maternal alcohol consumption during pregnancy and certain birth defects, the research into the treatment of FASD has become increasingly sophisticated. The field has begun to explore the possibility of intervening at different levels, and animal studies have provided valuable insights into the pathophysiology of the disease, forming the basis for implementing potential therapies with increasingly precise mechanisms. The recent reports suggest that compounds that reduce the severity of neurodevelopmental deficits, including glial cell function and myelination, and/or target oxidative stress and inflammation may be effective in treating FASD. Our goal in writing this article was to analyze and synthesize current experimental therapeutic interventions for FASD, elucidating their potential mechanisms of action, translational relevance, and implications for clinical application. This review exclusively focuses on animal models and the interventions used in these models to outline the current direction of research. We conclude that given the complexity of the underlying mechanisms, a multifactorial approach combining nutritional supplementation, pharmacotherapy, and behavioral techniques tailored to the stage and severity of the disease may be a promising avenue for further research in humans.

Decrease of ESKAPE virulence with a cationic heme-mimetic gallium porphyrin photosensitizer: The Trojan horse strategy that could help address antimicrobial resistance.

INTRODUCTION: Emerging antibiotic resistance among bacterial pathogens has forced an urgent need for alternative non-antibiotic strategies development that could combat drug resistant-associated infections. Suppression of virulence of ESKAPE pathogens' by targeting multiple virulence traits provides a promising approach. OBJECTIVES: Here we propose an iron-blocking antibacterial therapy based on a cationic heme-mimetic gallium porphyrin (GaCHP), which antibacterial efficacy could be further enhanced by photodynamic inactivation. METHODS: We used gallium heme mimetic porphyrin (GaCHP) excited with light to significantly reduce microbial viability and suppress both the expression and biological activity of several virulence traits of both Gram-positive and Gram-negative ESKAPE representatives, i.e., S. aureus and P. aeruginosa. Moreover, further improvement of the proposed strategy by combining it with routinely used antimicrobials to resensitize the microbes to antibiotics and provide enhanced bactericidal efficacy was investigated. RESULTS: The proposed strategy led to substantial inactivation of critical priority pathogens and has been evidenced to suppress the expression and biological activity of multiple virulence factors in S. aureus and P. aeruginosa. Finally, the combination of GaCHP phototreatment and antibiotics resulted in promising strategy to overcome antibiotic resistance of the studied microbes and to enhance disinfection of drug resistant pathogens. CONCLUSION: Lastly, considering high safety aspects of the proposed treatment toward host cells, i.e., lack of mutagenicity, no dark toxicity and mild phototoxicity, we describe an efficient alternative that simultaneously suppresses the functionality of multiple virulence factors in ESKAPE pathogens.

The Impact of Prenatal Alcohol Exposure on the Autonomic Nervous System and Cardiovascular System in Rats in a Sex-Specific Manner.

BACKGROUND: Fetal Alcohol Spectrum Disorder (FASD) is a consequence of prenatal alcohol exposure (PAE) associated with a range of effects, including dysmorphic features, prenatal and/or postnatal growth problems, and neurodevelopmental difficulties. Despite advances in treatment methods, there are still gaps in knowledge that highlight the need for further research. The study investigates the effect of PAE on the autonomic system, including sex differences that may aid in early FASD diagnosis, which is essential for effective interventions. METHODS: During gestational days 5 to 20, five pregnant female Wistar rats were orally administered either glucose or ethanol. After 22 days, 26 offspring were born and kept with their mothers for 21 days before being isolated. Electrocardiographic recordings were taken on the 29th and 64th day. Heart rate variability (HRV) parameters were collected, including heart rate (HR), standard deviation (SD), standard deviation of normal-to-normal intervals (SDNN), and the root mean square of successive differences between normal heartbeats (RMSSD). Additionally, a biochemical analysis of basic serum parameters was performed on day 68 of the study. RESULTS: The study found that PAE had a significant impact on HRV. While electrolyte homeostasis remained mostly unaffected, sex differences were observed across various parameters in both control and PAE groups, highlighting the sex-specific effects of PAE. Specifically, the PAE group had lower mean heart rates, particularly among females, and higher SDNN and RMSSD values. Additionally, there was a shift towards parasympathetic activity and a reduction in heart rate entropy in the PAE group. Biochemical changes induced by PAE were also observed, including elevated levels of alanine transaminase (ALT) and aspartate aminotransferase (AST), especially in males, increased creatinine concentration in females, and alterations in lipid metabolism. CONCLUSIONS: PAE negatively affects the development of the autonomic nervous system, resulting in decreased heart rate and altered sympathetic activity. PAE also induces cardiovascular abnormalities with sex-specific effects, highlighting a relationship between PAE consequences and sex. Elevated liver enzymes in the PAE group may indicate direct toxic effects, while increased creatinine levels, particularly in females, may suggest an influence on nephrogenesis and vascular function. The reduced potassium content may be linked to hypothalamus-pituitary-adrenal axis overactivity.

Deciphering the Dual Role of Heligmosomoides polygyrus Antigens in Macrophage Modulation and Breast Cancer Cell Growth.

In our study, we explored how parasitic nematodes, specifically Heligmosomoides polygyrus, influence the immune response, focusing on their potential role in tumor growth. The study aimed to understand the mechanisms by which these parasites modify immune cell activation, particularly in macrophages, and how this might create an environment conducive to tumor growth. Our methods involved analyzing the effects of H. polygyrus excretory-secretory antigens on macrophage activation and their subsequent impact on breast cancer cell lines EMT6 and 4T1. We observed that these antigens significantly increased the expression of genes associated with both pro-inflammatory and anti-inflammatory molecules, such as inducible nitric oxide synthase, TNF-α, (Tumor Necrosis Factor) Il-6 (Interleukin), and arginase. Additionally, we observed changes in the expression of macrophage surface receptors like CD11b, F4/80, and TLR4 (Toll-like receptor 4). Our findings indicate that the antigens from H. polygyrus markedly alter macrophage behavior and increase the proliferation of breast cancer cells in a laboratory setting. This study contributes to a deeper understanding of the complex interactions between parasitic infections and cancer development, highlighting the need for further research in this area to develop potential new strategies for cancer treatment.

Rosa rugosa Low Caloric Fiber Protein Preparations Rich in Antioxidant Flavanols and Ellagitannins.

Defatted seed residues after the extraction of rose oil have their potential not fully described in the existing literature. The aim of this study was to determine and characterize the components important for the human body that are found in Rosa rugosa defatted seeds, including dietary fibers, proteins, selected minerals, polyphenols and antioxidant activity. Rosa rugosa seeds defatted with CO2 in supercritical conditions are a rich source of dietary fibers (approx. 65%) and proteins (15%); their macronutrients include the following: Ca (175.9), Mg (83.9), K (199.2) and Na (3.5 mg/100 g). They also contain polyphenols, including flavanols (0.9%) and total ellagic acid (0.5%), and they exhibit antioxidant activity (143.8 µM TAEC/g). Tellimagrandin I and II and rugosin A were found in the extracts, and ellagitannins with a yet-indeterminate structure were also present. The seeds also contained ellagitannin derivatives-galloyl-HHDP-glucose and bis-HHDP-glucose-at the same time, and they are characterized by a low-fat content-0.4%. The energy value of defatted rose seeds is about half the energy value of popular seeds used in the food industry. The findings of the present study suggest that defatted rosehip seeds, the by-product of rosehip processing, could be an important source of bioactive components like dietary fibers, flavanols, ellagitannins and mineral compounds. Therefore, defatted rose seeds are very promising and require further research, because they can potentially be used as a natural source of chemopreventive agents.

Novel BTEX-degrading strains from subsurface soil: Isolation, identification and growth evaluation.

Monoaromatic hydrocarbons such as benzene, toluene, ethylbenzene, and o, m, and p-xylenes (BTEX) are high-risk pollutants because of their mutagenic and carcinogenic nature. These pollutants are found with elevated levels in groundwater and soil in Canada at several contaminated sites. The intrinsic microbes present in the subsurface have the potential to degrade pollutants by their metabolic pathways and convert them to non-toxic products. However, the low subsurface temperature (5-10 °C) limits their growth and degradation ability. This study examined the feasibility of subsurface heat augmentation using geothermal heating for BTEX bioremediation. Novel potent BTEX-degrading bacterial strains were isolated from soil at 3.0, 42.6, and 73.2 m depths collected from a geothermal borehole during installation and screened using an enrichment technique. The selected strains were identified with Sanger sequencing and phylogenetic tree analysis, revealing that all the strains except Bacillus subtilis are novel with respective to BTEX degradation. The isolates, Microbacterium esteraromaticum and Bacillus infantis showed the highest degradation with 67.98 and 65.2% for benzene, 72.8 and 71.02% for toluene, 77.52 and 76.44% for ethylbenzene, and 74.58 and 74.04% for xylenes respectively. Further, temperature influence at 15 ± 1 °C, 28 ± 1 °C and 40 ± 1 °C was observed, which showed increased growth by two-fold and on average 35-49% more biodegradation at higher temperatures. Results showed that temperature is a positive stimulant for bioremediation, hence geothermal heating could also be a stimulant for in-situ bioremediation.

Eating habits and nutritional knowledge among amateur ultrarunners.

Introduction: Many studies concerning the diet of physically active people refer to individuals who run; however, the importance of nutrition in professional and amateur sports plays a different role. This study aimed to evaluate the nutritional behavior and knowledge of amateur ultrarunners. This study involved a group of 308 respondents (89 women and 219 men) aged 18 -65. It investigated the influence of the level of knowledge about nutrition, gender, education, and smoking on dietary food habits and eating frequency. Methods: The KomPAN questionnaire was used to determine the dietary habits, diet quality, lifestyle, and nutrition knowledge of ultramarathon runners. The nutrition knowledge influenced the eating habits and frequency of specific meals expressed as the Healthy Diet Index-10 (HDI-10) and Unhealthy Diet Index-14 (UDI-14). Results: In women with sufficient knowledge about nutrition, lower HDI-10 scores were observed compared to those with a good level of knowledge, while men did not show a similar relationship. However, the effect of smoking on the frequency of food intake in men was noted. Interestingly, male smokers had a lower UDI-14 score than non-smokers. Depending on the level of knowledge, female and male ultrarunners more often or less frequently used selected food products. In turn, no effect of education on the frequency of consumption of specific foods was observed. Discussion: Such different results are most likely caused by the specificity of the study group, which consisted of amateur runners. Additionally, the study looked at general eating habits, not those employed when preparing for marathons. In the future, more respondents should be surveyed, also taking into account nutrition during training.

[LC-MS/MS as a method for the determination of isoprostanes: a brief review]. / Technika LC-MS/MS jako metoda oznaczania izoprostanów: krótki przeglad literatury.

Isoprostanes are a large group of compounds formed as products of free radical oxidation of polyunsaturated fatty acids, which are isomers of prostaglandin. They are present in all body tissues and biological fluids in quantifiable concentrations. Since 2018, the determination of isoprostanes by chromatographic technique with mass spectrometry is the golden standard of the oxidative stress markers determination in relation to oxidative damage to lipids. The publication is a synthetic review of recently published articles on the use of isoprostanes as a marker of lipid peroxidation determined with the liquid chromatography with tandem mass spectrometry technique. It presents the results of research using isoprostanes as a marker in medicine, in monitoring people working in exposure to harmful substances and in lifestyle research. Med Pr. 2023;74(2):119-25.

Non-radioactive imaging strategies for in vivo immune cell tracking.

In vivo tracking of administered cells chosen for specific disease treatment may be conducted by diagnostic imaging techniques preceded by cell labeling with special contrast agents. The most commonly used agents are those with radioactive properties, however their use in research is often impossible. This review paper focuses on the essential aspect of cell tracking with the exclusion of radioisotope tracers, therefore we compare application of different types of non-radioactive contrast agents (cell tracers), methods of cell labeling and application of various techniques for cell tracking, which are commonly used in preclinical or clinical studies. We discuss diagnostic imaging methods belonging to three groups: (1) Contrast-enhanced X-ray imaging, (2) Magnetic resonance imaging, and (3) Optical imaging. In addition, we present some interesting data from our own research on tracking immune cell with the use of discussed methods. Finally, we introduce an algorithm which may be useful for researchers planning leukocyte targeting studies, which may help to choose the appropriate cell type, contrast agent and diagnostic technique for particular disease study.

Attitudes Toward Organ Transplantation.

BACKGROUND: The purpose of transplantation is to improve the health or save the life of the recipient. Although organ transplantation is a method generally accepted by society, there are still people who, referring to moral and ethical aspects, reject its validity. A great threat to transplantology is also the lack of knowledge of the society resulting from insufficient education. AIM: The aim of this study was to find out attitudes and opinions about organ transplantation and to determine the level of acceptance of organ and tissue transplantation. METHODS: The tool chosen for the study was a survey questionnaire. The research group consisted of 200 people. Approval from the Bioethics Committee was obtained to conduct the study. RESULTS: The studies showed that more than half of the respondents (57%) would agree to organ donation for transplantation after the death of a loved one. Age was found to be statistically significant (P = .001). Older people showed more doubts about transplantation than people under 30. Over 80% of respondents agreed that initiatives to educate the public about transplantation are needed. CONCLUSIONS: The respondents refer to transplantation positively as a method of treating and saving life, and more than half of respondents would agree to donate their organs for transplant after the death of a loved one. The majority of respondents described their attitude toward transplantation as positive, admitting that the objection to donating is due to the ignorance and too little awareness on the subject.

The spectrum of attitudes towards the spectrum of autism and its relationship to psychological distress in mothers of children with autism.

LAY ABSTRACT: Mothers of children on the autism spectrum experience high levels of emotional distress. Mothers cope with stress by having their own thoughts and opinions about their children. In this study, we tested whether the way mothers perceive autism may contribute to the level of distress they feel. Some mothers see autism as a developmental disorder that needs to be cured, but some see autism as a type of mind that needs to be accepted. Our findings showed that mothers who see autism more as a type of mind are generally less stressed. But we also showed that it matters how severe are the child's symptoms, and how heavy was the perceived burden of caring for the child. These results imply that it is worth working on attitudes towards autism to help mothers cope better. But at the same time, we argue that mothers should not be judged for their perceptions of autism, as there is a huge spectrum of a child's characteristics and family's life circumstances.

Looking through rainbow-rimmed glasses: Taking neurodiversity perspective is related to subjective well-being of autistic adults.

LAY ABSTRACT: Autistic adults experience a high level of distress. Finding new ways to support their well-being is an important goal for researchers and clinicians. We assessed the way autistic adults view their autism, as a disorder or as a type of mind (neurodiversity), and the level they integrate with other autistic people, and we checked how those factors contribute to their well-being. People who see autism rather as a type of mind than as a disorder had higher self-esteem. People who view themselves as more similar to other autistic people felt more stressed, but this result was not accurate for people who view autism as a type of mind. Clinicians should be sensitive to the way autistic people understand autism and to what extent they identify with the autism community, because it may relate to their well-being.

Modulating the activity of fluoropyrimidines against colorectal cancer by Vitamin D and its analogs.

Colorectal cancer (CRC) is the third most common malignancy worldwide and the second most deadly cancer. Scientists have projected that by 2040, the prevalence will reach up to 3.2 million new cases annually due to population aging, disadvantageous diet transformations, and elevated exposure to risk factors. In the past decades, the five-year survival rate in colorectal cancer has significantly increased to 65% due to the development of an early endoscopic diagnosis and new chemotherapeutic approaches. Fluoropyrimidines, such as 5-fluorouracil or capecitabine, are commonly used to treat CRC. One of the most fundamental mechanisms of 5-FU is based on the inhibition of thymidylate synthase. This action is responsible for the therapeutic, but also toxic, effects of the drug. In this short review, we discuss the possible effects of vitamin D activity on colorectal cancer cells in relation to fluoropyrimidines. PubMed, Embase, and Web of Science databases were searched up to January 2022 for studies on vitamin D and 5-fluorouracil interaction mechanisms. Original studies, case reports, and review articles were included. Vitamin D or its analogs target multiple biochemical pathways and modulate numerous pathophysiological mechanisms in the course of colon cancer, including those related to the pharmacological sites of fluoropyrimidines. However, the available data concerning vitamin D-fluoropyrimidine pharmacological interactions are limited, especially regarding patients suffering from colon cancer and being treated with fluoropyrimidines.s.

Development and Assessment of Professional Competences among Polish Nursing Students during a 3-Year Education Cycle Trying.

The essence of the profile of nursing professional competences are basic behavioral characteristics, as well as mastering practical skills. The aim of this study was determination of the development of professional competences of perceiving a patient by first-, second-and third-year students of licentiate nursing study. The study was of a longitudinal character, and lasted for 3 years. The research instrument used was the Ascent to Competence Scale, and traditional assessment of students' knowledge and skills. A statistically significant relationship was observed between the average grade in practical education from all three years, and competences in student-teacher relationship. Higher grades in theoretical education were accompanied by lower results obtained by students in the area of nursing competences. The respondents' opinions concerning the development of knowledge and professional skills were relatively high among first-year students, which may be related with a sharp increase in nursing knowledge, whereas third-year students considered it important to perceive a considerable development of professional competences. The results of this study can help in the design of education programs meeting quality standards, and alignment with students and population health needs, which is adequate to the assumptions of the WHO Global Strategic Directions for Nursing and Midwifery 2021-2025.

Zeolite-Supported Aggregate as Potential Antimicrobial Agents in Gypsum Composites.

Relatively easy treatment of glass aggregates can lead to the formation of a highly porous zeolite aggregate. This study focuses on the possibility of using such an aggregate as an active additive to a gypsum binder. The physical properties of hardened gypsum composites with zeolite fillers doped with various metal ions (Ni2+, Cu2+, and Zn2+) have been compared. In addition to studies of the basic physical properties of the composites, structural and microstructural studies as well as antimicrobial tests were performed. It was found that the parameters of the composites with the addition of various ions do not differ significantly from the reference but modifies the microstructure. Among other things, the ions analyzed reduce the microporosity of gypsum composites. Using all aggregates, a product with adequate strength (above 2 MPa) and thermal conductivity (about 0.35 W/m·K) appropriate for typical lightweight gypsum composites can be obtained. The bacteriostatic effect of formulations with copper and zinc against Escherichia coli and with copper against Staphylococcus aureus was found.

Great Minds Think Alike? Spatial Search Processes Can Be More Idiosyncratic When Guided by More Accurate Information.

Existing research demonstrates that pre-decisional information sampling strategies are often stable within a given person while varying greatly across people. However, it remains largely unknown what drives these individual differences, that is, why in some circumstances we collect information more idiosyncratically. In this brief report, we present a pre-registered online study of spatial search. Using a novel technique that combines machine-learning dimension reduction and sequence alignment algorithms, we quantify the extent to which the shape and temporal properties of a search trajectory are idiosyncratic. We show that this metric increases (trajectories become more idiosyncratic) when a person is better informed about the likely location of the search target, while poorly informed individuals seem more likely to resort to default search routines determined bottom-up by the properties of the search field. This shows that when many people independently attempt to solve a task in a similar way, they are not necessarily "onto something."

Exploring the governing transport mechanisms of corrosive agents in a Canadian deep geological repository.

All nuclear energy producing nations face a common challenge associated with the long-term solution for their used nuclear fuel. After decades of research, many nuclear safety agencies worldwide agree that deep geological repositories (DGRs) are appropriate long-term solutions to protect the biosphere. The Canadian DGR is planned in either stable crystalline or sedimentary host rock (depending on the final site location) to house the used nuclear fuel in copper-coated used fuel containers (UFCs) surrounded by highly compacted bentonite. The copper-coating and bentonite provide robust protection against many corrosion processes anticipated in the DGR. However, it is possible that bisulfide (HS-) produced near the host rock-bentonite interface may transport through the bentonite and corrode the UFCs during the DGR design life (i.e., one million years); although container performance assessments typically account for this process, while maintaining container integrity. Because the DGR design life far exceeds those of practical experimentation, there is a need for robust numerical models to forecast HS- transport. In this paper we present the development of a coupled 3D thermal-hydraulic-chemical model to explore the impact of key coupled physics on HS- transport in the proposed Canadian DGR. These simulations reveal that, although saturation delayed and heating accelerated HS- transport over the first 100s and 10,000s of years, respectively, these times of influence were small compared to the long DGR design life. Consequently, the influence from heating only increased total projected HS- corrosion by <20% and the influence from saturation had a negligible impact (<1%). By comparing the corrosion rate results with a simplified model, it was shown that nearly-steady DGR design parameters governed most of the projected HS- corrosion. Therefore, those parameters need to be carefully resolved to reliably forecast the extent of HS- corrosion.

Association of allelic combinations in selenoprotein and redox related genes with markers of lipid metabolism and oxidative stress - multimarkers analysis in a cross-sectional study.

BACKGROUND: Selenium (Se) and selenoproteins have been shown to be involved in lipid metabolism mainly due to their ability to modulate redox homeostasis in adipose tissue. The underlying mechanisms are yet to be evaluated. In the light of few data related to the association between polymorphic variants of selenoprotein encoding genes and metabolic syndrome or obesity in humans, the role of selenoprotein polymorphisms in lipid metabolism remains unclear. The aim of this study was to investigate the impact of allelic combination within selenoprotein and redox related genes on the markers of lipid metabolism and oxidative stress. METHODS: The study comprised 441 healthy individuals from Poland, in the 18-74 year age group. Allelic combinations were investigated within the polymorphic variants of four selenoprotein encoding genes (GPX1 rs1050450, GPX4 rs713041, SELENOP rs3877899 and SELENOF rs5859) and the redox related gene (SOD2 rs4880). The impact of the most common allelic GPX1-GPX4-SELENOP-SELENOF-SOD2 combinations was assessed on the following markers: triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), glutathione peroxidase activities (GPX1, GPX3), lipid peroxidation (as TBARS), ceruloplasmin (Cp) and superoxide dismutase 1 (SOD1). RESULTS: Multivariable analysis revealed significant associations between three allelic combinations and markers of lipid metabolism, including HDL-C and TC/HDL-C ratio (AAAAa), LDL-C (aaAaa), and triglycerides (aaaaA), whereas two allelic combinations (aAaAA, aaaAA) were associated with GPX3 activity. CONCLUSION: This study confirms the possible implication of selenoproteins in lipid metabolism and warrants further research on specific allele combinations within selenoprotein and redox related genes in order to identify functional genetic combinations linked to metabolic phenotype.