Impact of lipidation site on the activity of α-helical antimicrobial peptides.

Antimicrobial peptides (AMPs) display advantages over traditional antibiotics due to their broad spectrum of activity against various pathogens, and may even overcome bacterial drug resistance. However, despite their potential therapeutic benefits, widespread application of AMPs is limited by their instability, sensitivity to high salt concentrations, toxicity, and immunogenicity. Lipidation is a promising strategy in overcoming these drawbacks and potential problems for drug candidates. While N-terminal lipidation is a well-studied form of acylation of biologically active peptides, fatty acylation of the lysine side chain has still been poorly explored. In this study, we examined systematic introduction of octanoic (C8) or decanoic (C10) acid into the sequences of three antimicrobial α-helical peptides, namely LL-I, LK6, and ATRA-1, by acylation of subsequent lysine residues, resulting in 17 lipopeptides. Fatty acid lengths optimal for antimicrobial activity were selected based on a previous study on the N-terminal lipidated counterparts of these peptides. Shuffling the position of the fatty acid tails in the sequences of the peptides preserved high activity against Gram-positive bacteria, increased activity against Gram-negative strains and reduced cytotoxicity, compared to the N-terminal acylated counterparts. In the case of the LL-I and LK6 conjugates, the interactions with artificial negatively charged membranes induced formation of an α-helical structure but without a direct correlation between helicity and amphipathicity. Unexpectedly, the ATRA-1 derivatives showed only a small tendency, if any, to adopt a helical structure upon binding to POPG vesicles, which may indicate a non-helical active conformation. A more detailed study of the selected analogues, namely LL-I-4C8, LK6-7C8, and ATRA-1-11C10, provided evidence of a tendency to self-assemble into clumped and/or isolated fibrils, micelles or clusters of micelles, and proved that the lipid bilayer is the main target of action of the tested lipopeptides. In summary, the results of the present study highlight that alternative conjugation sites for lipid modification of AMPs, rather than the commonly applied N-terminal conjugation site, may improve the selectivity of action and be feasible in testing for the development of new lipid-peptide conjugates.

Opinions of Polish postgraduate nursing students on medical humanization courses in relation to age, years of service, and nursing specialty.

BACKGROUND: The Polish educational system for nurses has undergone a substantial transformation over the past two decades, with the introduction of a mandatory university education that encompasses humanization in medicine. Consequently, nurses who had been licensed to practice before the implementation of the reform returned to universities to pursue master's degrees alongside their younger colleagues who had only recently obtained bachelor's degrees. This distinctive learning environment, in which nurses of varying ages and years of practice study together, offers an opportunity to gain insight into their perspectives on the educational process. Accordingly, the present study aims to examine the opinions of Polish postgraduate nursing students at one university regarding medical humanization courses, focusing on the extent to which these opinions are shaped by age, years of service, and specialty of nursing care. METHODS: From February to June 2023, an anonymous survey was conducted on the university's online platform, involving 89 out of 169 participants in the master's degree nursing program. The newly designed questionnaire comprised 15 primary questions and 11 metric questions. RESULTS: The study population consisted of registered nurses with a mean age of 35 years (ranging from 22 to 54 years). The majority of participants were women (97.8%). The analysis revealed that older students (Spearman's rho 0.480, p < 0.001) and those with more years of professional experience (Spearman's rho 0.377, p < 0.001) perceived humanizing classes as a vital component of nurse training and work. Younger and less experienced students did not share this perspective. Specialization status was also identified as a differentiating factor (Chi² = 10.830, p < 0.05). However, other characteristics, including the number of positions held during the survey, the type of position, the primary employer, and the nature of work (shift or non-shift), did not exhibit statistically significant differentiation among participants. CONCLUSIONS: This study found age- and work-experience-related differences in nursing students' opinions toward courses teaching humanization in health care. The results suggest that changing the teaching format and involving older and more experienced students in sharing experiences with younger and less experienced students could potentially improve the implementation of learned skills in clinical practice.

Expectations of Polish undergraduate medical students for medical humanities classes: a survey-based pilot study.

BACKGROUND: Medical schools teach Medical Humanities (MH) to provide students with knowledge about the human experience related to health, illness, disease, medicine, and healthcare. Due to the previously observed negative opinions about MH courses, we examined the expectations of medical students in Poland toward humanities subjects. METHODS: We conducted a voluntary, anonymous electronic survey in one medical school (single-center study) and collected data from 166 medical students. The results were analyzed by comparing continuous and categorical variables between groups (gender, year of study, previous participation in MH classes). RESULTS: The students expected to learn how to communicate with patients and their families, especially about difficult topics. They also expected the classes to be active, stress-free, and without passing grades. The preferred MH teacher was a physician, although choosing a psychologist or other qualified person as an MH teacher was also popular. Previous participants in MH courses were more likely to expect such a course to be compulsory than those who had yet to attend it. CONCLUSION: Considering the students' expectations when designing MH classes could increase students' satisfaction with MH courses.

Lipidation of Naturally Occurring α-Helical Antimicrobial Peptides as a Promising Strategy for Drug Design.

In this paper, we describe the chemical synthesis, preliminary evaluation of antimicrobial properties and mechanisms of action of a novel group of lipidated derivatives of three naturally occurring α-helical antimicrobial peptides, LL-I (VNWKKVLGKIIKVAK-NH2), LK6 (IKKILSKILLKKL-NH2), ATRA-1 (KRFKKFFKKLK-NH2). The obtained results showed that biological properties of the final compounds were defined both by the length of the fatty acid and by the structural and physico-chemical properties of the initial peptide. We consider C8-C12 length of the hydrocarbon chain as the optimal for antimicrobial activity improvement. However, the most active analogues exerted relatively high cytotoxicity toward keratinocytes, with the exception of the ATRA-1 derivatives, which had a higher selectivity for microbial cells. The ATRA-1 derivatives had relatively low cytotoxicity against healthy human keratinocytes but high cytotoxicity against human breast cancer cells. Taking into account that ATRA-1 analogues carry the highest positive net charge, it can be assumed that this feature contributes to cell selectivity. As expected, the studied lipopeptides showed a strong tendency to self-assembly into fibrils and/or elongated and spherical micelles, with the least cytotoxic ATRA-1 derivatives forming apparently smaller assemblies. The results of the study also confirmed that the bacterial cell membrane is the target for the studied compounds.

A study of opinions about the Polish constitutional tribunal's judgement strengthening Polish abortion laws.

OBJECTIVE: In October 2020, the Polish Constitutional Tribunal (CT) ruled that in cases where there are indications of irreversible impairments of a foetus or incurable life-threatening diseases, abortions violate the Polish Constitution. Despite the fact that it was issued during the second wave of the SARS-CoV-2 pandemic in Poland, this judgement caused numerous protests. The current study sought to ascertain Poles' opinions regarding the CT's judgement, and the ensuing threat to public health presented by the protests against it. MATERIAL AND METHODS: An online survey was conducted on a quota sample of adult Poles (N = 1072). The sample reflected the population structure of Poland. RESULTS: Only 15.5% of the people surveyed agreed that the CT's judgement was correct. Logistic regression analysis showed that support for the CT's ruling could be predicted by male gender, more frequent participation in religious practices, and the presence of a greater number of children in household. The majority of people (65.1%) considered protests to be necessary despite the ongoing pandemic. Cluster analysis distinguished between two groups of people, which were labelled "moderate liberals" (43.9%) and "moderate conservatives" (56.1%). There were no extreme groups - neither one that supported the CT's judgement and condemned the protesters, nor one that supported protesters unconditionally and disagreed with the judgement. CONCLUSIONS: Undoubtedly, there is no consensus among Poles on the issue of abortion, but the CT's judgement, resulted in a high level of agreement between people with different views.

Double-Headed Cationic Lipopeptides: An Emerging Class of Antimicrobials.

Antimicrobial peptides (AMPs) constitute a promising tool in the development of novel therapeutic agents useful in a wide range of bacterial and fungal infections. Among the modifications improving pharmacokinetic and pharmacodynamic characteristics of natural AMPs, an important role is played by lipidation. This study focuses on the newly designed and synthesized lipopeptides containing multiple Lys residues or their shorter homologues with palmitic acid (C16) attached to the side chain of a residue located in the center of the peptide sequence. The approach resulted in the development of lipopeptides representing a model of surfactants with two polar headgroups. The aim of this study is to explain how variations in the length of the peptide chain or the hydrocarbon side chain of an amino acid residue modified with C16, affect biological functions of lipopeptides, their self-assembling propensity, and their mode of action.

[Characteristic of AMP and the effects of chemical modifications on the modulation of their antimicrobial properties]. / Charakterystyka peptydów przeciwdrobnoustrojowych oraz wplyw modyfikacji chemicznych na modulowanie ich aktywnosci biologicznej.

Antibiotics have revolutionized the pharmacology market but their "golden area" passed away. The urgent need to develop new medicins with the mechanism of action different than those already used is constantly growing because of the drug-resistance of pathogenic microorganisms. The observed increasing resistance of microbes motivates scientists to design innovative strategies based on the natural peptides that exhibit antimicrobial activity. In this article we present general characterization of antimicrobial peptides and effects of chemical modifications on the modulation of their antimicrobial properties.

Does growing up with a physician influence the ethics of medical students' relationships with the pharmaceutical industry? The cases of the US and Poland.

BACKGROUND: Medical schools have a major impact on future doctors' ethics and their attitudes towards cooperation with the pharmaceutical industry. From childhood, medical students who are related to a physician are exposed to the characteristics of a medical career and learn its professional ethics not only in school but also in the family setting. The present paper sought to answer the research question: 'How does growing up with a physician influence medical students' perceptions of conflicts of interest in their relationships with industry?' METHODS: An anonymous questionnaire was completed by 451 medical students from four Philadelphia medical schools and 554 medical students from Warsaw Medical University during 2013. Medical schools in these two cities were chosen because they are both university cities with similar population sizes. Students who had and who did not have a family member working as a physician were compared using chi-square analysis. Data were analysed for each country separately. RESULTS: For both the US and Poland, there were statistically significant differences (p < .05) between medical students with a physician as a family member and other students with respect to views regarding relationship with the pharmaceutical industry. In both groups, this difference occurred for three important dimensions: students' relationship with the pharmaceutical industry; students' views on physicians' rights to cooperate with the pharmaceutical industry; trust in the pharmaceutical industry. In the US, students related to a doctor were characterized by more restrictive opinions on all three dimensions than other students (e.g., 27.8% of the former students vs. 31.4% of the latter students thought doctors had unrestricted rights to cooperate with the industry). However, the contrary was observed in Poland: students with a physician in the family had less strict views than their colleagues (e.g., 56.8% of the former vs. 39.7% of the latter thought that doctors should have unrestricted rights of cooperation). CONCLUSIONS: In Poland, a former communist country, physicians transmit a more liberal approach towards collaboration with the pharmaceutical industry to their student relatives than those in the US.

[The role of proprotein convertases in cancer diseases with particular focus on PACE4]. / Rola konwertaz probialkowych w chorobach nowotworowych ze szczególnym uwzglednieniem enzymu PACE4.

Cancer is one of the most common cause of death nowadays. Thorough knowledge of the mechanisms of tumorigenesis and invasiveness of tumor cells is crucial for the development of molecular targeted therapies, which are believed to be future treatment of this type of diseases. Proteolytic enzymes are one of the factors involved in the development of cancer cells, very often used as markers of tumor progression. In this paper we describe the role of enzymes termed proprotein convertases (PCs) in pathogenesis and progress of cancer diseases. Furthermore, we indicate potential directions for the development of therapeutic strategies designed based on PCs inhibitors.

TELEVISION ADVERTISING OF SELECTED MEDICINAL PRODUCTS IN POLAND AND IN THE UNITED STATES - A COMPARATIVE ANALYSIS OF SELECTED TELEVISION COMMERCIALS.

The aim of the analysis was to establish the differences between television commercials of OTC drugs broadcast in Poland and in the U.S. The study covered 100 commercials of medicinal products of various producers applied to treat a variety of symptoms and diseases. The analysis demonstrated that there are both similarities and differences. The differences concerned e.g., spot length, the time of placement of a brand name and the diversity of advertising slogans. The most significant similarities concerned applied manipulation techniques, locations featured in commercials and the choice of actors.

Interactions between doctors and pharmaceutical sales representatives in a former communist country. The ethical issues.

An anonymous survey distributed to doctors in Poland revealed the troublesome relationship between physicians and pharmaceutical sale representatives in terms of the frequency of visits, the trust of physicians in information supplied by sales reps, gifts accepted, and the general influence of marketing strategies on physician decisions. Challenges remain, despite laws enacted to address the problem.

Generational Differences in Food Choices and Consumer Behaviors in the Context of Sustainable Development.

(1) Background: This study examines diverse food choices and sustainable consumption behavior across four generations of Poles: Baby Boomers, Generation X, Generation Y, and Generation Z. (2) Methods: The research employed an online survey with a quota sample of 1000 individuals, representing the Polish population in terms of gender, residence, and education (categorized into two groups). (3) Results: For Poles, the crucial factors in food selection were product quality (69.0%), price (68.6%), and information about the product's composition (41.0%). Older cohorts (Baby Boomers and Generation X) prioritized food quality, while younger generations (Generation Y and Generation Z) emphasized price. Statistically significant differences emerged between generations regarding the product's country of origin, with older generations emphasizing its importance more. The oldest group (Baby Boomers) considered ecological certification most important. As much as 85.9% of Poles checked product expiration dates while buying products, and 82.8% bought only as much as they needed. Baby Boomers most often exhibited these two behaviors and can be considered the most responsible among all generations. (4) Conclusions: This article highlights the importance of comprehensive sustainability efforts in the context of food choices. It takes into account the socio-cultural and historical circumstances of each generation that influence their consumer habits.

What can public endorsement for a smoking ban policy mean? Preliminary findings from a qualitative study.

OBJECTIVES: The aim of the study is to describe attitudes which underlie Pole's declarations of support for a smoking ban in public places. METHODS: The qualitative study using semi-structured individual in-depth interviews was conducted. The 30 IDI-s (in depth interviews) being a part of a larger research project entitled 'Lay meanings of health and life orientation of Polish society versus prevention and health promotion attitudes' were realized between 2007-2009. People belonging to all key socio-demographic categories identified by variables such as sex, age, education, and place of domicile were interviewed. The resulting material was subjected to content analysis. In the study the structural concept of 'attitude' was adopted. In order to identify the attitudes towards smoking bans in public places statements related to all three components of attitudes were analysed, but the typology of attitudes was constructed mainly on the basis of the emotional-evaluative component. RESULTS: The study identified as many as four attitudes behind the declared support for a smoking ban in public places. Those attitudes were labelled 'supportive', 'accepting', 'conditionally accepting', and 'ambivalent'. They differ as regards degree of acceptance for the ban, conviction about harmfulness of passive smoking, setting great store by other regulators of smoking like cultural norms or healthy consciousness, and propensity to observe and execute the smoking ban. The 'supportive' attitude can be characterized not only by total support for the smoking ban in public places but also by insistence on the need for its extension. The 'accepting' attitude means approval for the smoking ban, and the 'conditionally accepting' attitude is distinguished from the others by the stress put on the right of smokers to have an access to places where smoking is permitted. The 'ambivalent' attitude can be typified by underlining other than legal ways of influencing smoking in public places. CONCLUSIONS: The study suggests that the attitudes underlying the Pole's declarations of support for a smoking ban in public places can be differentiated. However, because of the low number of participants in the study the results should be verified thus the further research is needed. Therefore, there is a need not only to study people's declaration of support or objection for the smoking ban in public places but also to examine their attitudes including cognitive and behavioural components using both qualitative and quantitative methods of social research.

How Polish medical students are socialised to cooperate with the pharmaceutical industry: a focus group study of the importance of informal, hidden and null curricula.

This study analysed how Polish medical students are socialised to cooperate with the pharmaceutical industry via informal, hidden, and null curricula. Nine focus groups were run with medical students in their second year and upwards at three Polish medical universities. Initially, most students had difficulty in discerning pharmaceutical companies' presence in their education, but on reflection they all recognised this presence. Students said that they were surrounded by small medical gifts provided by companies, met pharmaceutical representatives, and took part in events for physicians organised and/or sponsored by the pharmaceutical industry. Nevertheless, they did not think they were the main target of the industry's marketing activities, saying that these were largely aimed at practicing doctors, and that they were only targeted as opportunities arose. Students' statements make it clear that their socialisation takes place within a culture which consents to medical professionals' cooperation with the industry. Medical students come to perceive cooperation with the industry as natural, and benefits from the industry as a privilege of doctors. Medical schools can prevent this by introducing guidelines, conflict of interest polices, and changing the formal curriculum, but the need for such measures is not currently recognised in Poland.

Changes in intensification of religious involvement during the COVID-19 pandemic in Poland.

INTRODUCTION: The emergence of the virus Sars-CoV-2, and subsequent COVID-19 pandemic, caused a global threat to public health. In such challenging and worrying situations it can be expected that people will seek comfort in religion. However, before the pandemic there were never such wide world disruptions of religious practice-because of social distancing regulations, religiosity cannot be practiced in the same way as it was before the pandemic. METHODS: Two anonymous online surveys were conducted of adult Poles, one during the second wave (N = 1072; November 2020) and one during the third wave of the pandemic (N = 1080; April 2021). The survey samples of participants reflected the Polish population structure in terms of age, sex, size of place of residence, education, and province. RESULTS: Participation in institutional religious practices fell threefold to 11.9% during the pandemic, as compared to pre-pandemic times (31.2%). The number of people who did not go to church at all increased from 23.1% to 57.0%. Between the second and third waves, there was a small return to regular practice (from 10.1% to 14.1%). Based on the subjective assessment of the amount of time devoted to prayer, fewer people reporting an increase (10.6%) than a decrease (20.1%) in religious commitment during the pandemic. Logistic regressions showed that an increase in religious commitment can be predicted by older age, more frequent participation in religious practices before the pandemic, and higher life satisfaction. A decrease in religious commitment can be predicted by younger age, less frequent participation in religious practices before the pandemic, and greater number of children in the household. CONCLUSION: Our research indicates a deintensification of religious practices during the COVID-19 pandemic in Poland. The pandemic has accelerated process of polarization of Polish religiosity.

Transparency or restricting gifts? Polish medical students' opinions about regulating relationships with pharmaceutical sales representatives.

Relationships between physicians and pharmaceutical sales representatives (PSRs) often create conflicts of interest, not least because of the various benefits received by physicians. Many countries attempt to control pharmaceutical industry marketing strategies through legal regulation, and this is true in Poland where efforts are underway to eliminate any practices that might be considered corrupt in medicine. The present research considered Polish medical students' opinions about domestic laws restricting doctors' acceptance of expensive gifts from the industry, the idea of compulsory transparency, and the possibility of introducing a Polish Sunshine Law. A qualitative, focus group-based, interview method was used. Data were gathered from nine focus groups involving 92 medical students from three universities located in major Polish cities. The article presents a classification of opposing student views with regard to the consequences of introducing different legal solutions; this should be useful for policy makers deliberating on how to optimally regulate pharmaceutical marketing. The study's results are discussed in the context of the public bioethical debate in Poland.

Trust in Medicine as a Factor Conditioning Behaviors Recommended by Healthcare Experts during the COVID-19 Pandemic in Poland.

OBJECTIVE: Due to the COVID-19 pandemic, public health experts have faced the challenge of convincing people to change their everyday habits. This study aims to evaluate the impact of trust in medicine on Polish citizens' adherence to recommended behaviors. METHODS: An online survey was conducted on a quota sample of adult Poles (n = 1072) during the second wave of COVID-19. RESULTS: The trust-in-medicine index was created from statements relating to trust in healthcare professionals, vaccines, and medicines. This index showed that 27.1% of respondents expressed low trust, 36.7% expressed moderate trust, and 36.3% expressed high trust. The recommended behavior index was created from nine statements. This index showed that 15.8% of respondents had low adherence, 38.2% had moderate adherence, and 46.0% had high adherence to the healthcare experts' recommendations. One-way analysis of variance showed that people with a high trust had significantly higher scores on the recommended behavior index when compared to people with a moderate or low trust. CONCLUSIONS: This study suggests that those responsible for health policy should put more effort into building trust not only in health professionals, but also in pharmaceutical companies. We also determined the socio-demographic features of people to whom such actions of trust building should be directed.

Perception of Medical Humanities among Polish Medical Students: Qualitative Analysis.

Medical humanities (MH) courses are a critical element of the medical curriculum influencing the establishment of a physician in the medical profession. However, the opinion about MH among medical students remains unknown. Interviews from seven focus groups were analysed. The students attended one of three Polish medical schools in Gdansk, Krakow, and Warsaw and were recruited to the discussion focused on the impact of drug manufacturers' presence at medical universities on socialization in the medical profession. Thematic analysis was conducted using the theoretical framework of social constructivism. The students' opinions about the MH classes arose during the analysis. In six groups, students thought that MH courses would be helpful in their future medical practice. However, in four groups, different opinion was expressed that MH courses were unnecessary or even "a waste of time". Factors discouraging students from the MH classes included poorly taught courses (monotonous, uninteresting, unrelated to medical practice, taught by unsuitable lecturers). Secondly, students thought that the time investment in the MH was too extensive. Furthermore, curriculum problems were identified, reflecting the incompatibility between the content of MH courses and teaching semesters. Lastly, some students stated that participation in MH courses should be elective and based on individual interests. Addressing problems recognized in this work could improve the training of future Polish physicians.

A Qualitative Study of the Mistreatment of Medical Students by Their Lecturers in Polish Medical Schools.

OBJECTIVE: To describe experiences of mistreatment among Polish medical students. METHODS: Nine focus groups were carried out with 92 students from three medical universities in Poland (in Gdansk, Krakow, and Warsaw). RESULTS: The mistreatment of medical students included verbal abuse, disregard, and obstacles to pass exams. Students experienced humiliation, belittlement, insults, criticism, shouting, and indecent comments. The lecturers did not respect the students' time; they did not show understanding for their absences; sometimes, they came to class unprepared while other times, they showed indifference regarding the well-being of students. Respondents stated that they were given enormous amounts material such that they found it far beyond their ability to learn; they were not given information about which textbooks were to be used; exams were incredibly detailed and difficult; and the grading system was unfair. In general, most students did not report the mistreatment. The respondents noticed the negative consequences of their mistreatment, which included a decrease in self-esteem and increased levels of anxiety and stress. This may translate into a lack of empathetic approach to patients. CONCLUSIONS: The phenomenon of the mistreatment of medical students requires more attention in Poland. It is important to raise awareness of the significant consequences of this.

A Typology of Poles' Attitudes toward COVID-19 during the First Wave of the Pandemic.

(1) Objective: To explore Poles' attitudes during the first wave of COVID-19 pandemic in 2020 as a contribution toward the creation of effective health policies. (2) Method: Computer-assisted web interviewing (CAWI) was used to survey a sample of 1001 Poles selected using quota sampling. (3) Results: Using cluster analysis, three types of attitudes were distinguished, people being classified as "involved" (48.1%), "cautious" (27.4%), or "indifferent" (24.6%). The result of greatest interest was the absence of any attitude indicating an extremely dismissive posture toward COVID-19. Three logistic regression analyses, comparing people displaying each attitude with those comparing the other two attitudes combined, showed that an involved attitude was likely to be associated with being female, being in a poorer financial situation, but having relatively high life satisfaction. A cautious attitude was more likely to appear in places with fewer residents and among people in a favorable financial situation, and that an indifferent attitude was more likely to be associated with being male and having lower life satisfaction. (4) Conclusions: The attitudes identified may help to explain why, during the spring of 2020, the virus was spreading slightly more slowly, and on a narrower scale, in Poland than in other countries.