Estrogen Receptor Signaling in Breast Cancer.

Estrogen receptor (ER) signaling is a critical regulator of cell proliferation, differentiation, and survival in breast cancer (BC) and other hormone-sensitive cancers. In this review, we explore the mechanism of ER-dependent downstream signaling in BC and the role of estrogens as growth factors necessary for cancer invasion and dissemination. The significance of the clinical implications of ER signaling in BC, including the potential of endocrine therapies that target estrogens' synthesis and ER-dependent signal transmission, such as aromatase inhibitors or selective estrogen receptor modulators, is discussed. As a consequence, the challenges associated with the resistance to these therapies resulting from acquired ER mutations and potential strategies to overcome them are the critical point for the new treatment strategies' development.

The Role of Sirtuin 6 in the Deacetylation of Histone Proteins as a Factor in the Progression of Neoplastic Disease.

SIRT6 is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, predominantly located in the nucleus, that is involved in the processes of histone modification, DNA repair, cell cycle regulation, and apoptosis. Disturbances in SIRT6 expression levels have been observed in the development and progression of various types of cancer. Therefore, it is important to better understand the role of SIRT6 in biochemical pathways and assign it specific biological functions. This review aims to summarize the role of SIRT6 in carcinogenesis and tumor development. A better understanding of the factors influencing SIRT6 expression and its biological role in carcinogenesis may help to develop novel anti-cancer therapeutic strategies. Moreover, we discuss the anti-cancer effects and mechanism of action of small molecule SIRT6 modulators (both activators and inhibitors) in different types of cancer.

The role of life skills in developing an authentic leadership attitude in public health students: a multicenter cross-sectional study in Poland.

BACKGROUND: Decision-making skills are considered crucial life skills that condition proper social functioning within groups (i.e., support authentic leadership skills and increasing one's chances of success and wellbeing in life). Nonetheless, the number of scientific papers addressing the role of life skills in developing authentic leadership skills in public health students is limited. The aim of the present study was to develop a theoretical model to determine the role of selected life skills in developing authentic leadership skills in public health students. METHODS: The study was conducted from January 16 through February 28, 2018. In total, 653 students undertaking in-service training in Master's degree programs qualified for the study, and complete data sets were obtained from 329 students (response rate 50.38%). The data were collected by means of a paper questionnaire. Four research tools were used in the study: The Authentic Leadership Self-Assessment Questionnaire, The Moral Foundations Questionnaire, The General Self-Efficacy Scale, and The Youth Leadership Life Skills Development Scale. RESULTS: Two subgroups were identified among the public health students in the study: 1) the extra life skills training group (N = 113) and 2) the no extra life skills training group (N = 216). Both groups of study participants did not differ significantly in terms of age (M (SD): 25.0 (3.89) vs. 25.0 (3.66); t = 0.068, P = 0.946). On the other hand, clear differences were observed in the case of the respondents' participation in voluntary service. The respondents from the extra life skills training group declared participation in voluntary activities less frequently than the respondents from the second identified group (48.7 vs. 31.9%). CONCLUSIONS: A verified theoretical model showed that course aimed at strengthening authentic leadership competences should be modular, should focus on self-improvement and critical reflection, and should be spread over time to enable and encourage each participant to grow and flourish at their own pace.

Antagonistic Interaction between Histone Deacetylase Inhibitor: Cambinol and Cisplatin-An Isobolographic Analysis in Breast Cancer In Vitro Models.

Breast cancer (BC) is the leading cause of death in women all over the world. Currently, combined chemotherapy with two or more agents is considered a promising anti-cancer tool to achieve better therapeutic response and to reduce therapy-related side effects. In our study, we demonstrated an antagonistic effect of cytostatic agent-cisplatin (CDDP) and histone deacetylase inhibitor: cambinol (CAM) for breast cancer cell lines with different phenotypes: estrogen receptor positive (MCF7, T47D) and triple negative (MDA-MB-231, MDA-MB-468). The type of pharmacological interaction was assessed by an isobolographic analysis. Our results showed that both agents used separately induced cell apoptosis; however, applying them in combination ameliorated antiproliferative effect for all BC cell lines indicating antagonistic interaction. Cell cycle analysis showed that CAM abolished cell cycle arrest in S phase, which was induced by CDDP. Additionally, CAM increased cell proliferation compared to CDDP used alone. Our data indicate that CAM and CDDP used in combination produce antagonistic interaction, which could inhibit anti-cancer treatment efficacy, showing importance of preclinical testing.

Magnoflorine-Isolation and the Anticancer Potential against NCI-H1299 Lung, MDA-MB-468 Breast, T98G Glioma, and TE671 Rhabdomyosarcoma Cancer Cells.

Magnoflorine (MGN) is a quaternary aporphine alkaloid that exhibits numerous therapeutic properties, including neuropsychopharmacological, anti-anxiety, immunomodulatory, anti-inflammatory, antioxidant, or antifungal activities. The aim of the present study was an investigation of the influence of MGN on viability, proliferation, induction of apoptosis, and cell cycle arrest in NCI-H1299 lung, MDA-MB-468 breast, T98G glioma, and TE671 rhabdomyosarcoma cancer cells. MGN was isolated from the roots of Berberis cretica L. by counter-current partition chromatography (CPC). Cell viability and proliferation assessments were performed by means of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and 5-bromo-2'-deoxyuridine (BrDU) assays, respectively. The induction of apoptosis and cell cycle progression was measured using fluorescence-activated cell sorting analysis. MGN in high doses inhibits proliferation, induces apoptosis, and inhibits cell cycle in S/G2 phases in a dose-dependent manner. MGN seems to be a promising anti-cancer compound in therapy of some types of lung, breast, glioma, and rhabdomyosarcoma cancers, for which current standard therapies are limited or have severe strong side effects.

Socioeconomic correlates and biochemical profiles of smokers in Poland: a cross-sectional study.

INTRODUCTION: Epidemiological studies have shown a fairly constant association between the socioeconomic status and smoking. However, associations between smoking and the biological indicators of health status have not been well described yet. OBJECTIVES: This study aimed to determine the relationship among smoking, biochemical risk factors, and sociodemographic characteristics in the Polish population. PATIENTS AND METHODS: A survey was carried out in a representative sample of Polish residents aged 18 to 79 years. A total of 2413 randomly selected subjects participated in the survey. Logistic regression analysis as well as parametrical and nonparametrical tests were performed. RESULTS: Significantly higher cholesterol, apolipoprotein B, and potassium levels were observed in smoking women and men compared with the nonsmoking population. Significantly lower bilirubin levels were noted in smoking individuals. Higher C­reactive protein and lower creatinine levels were reported only in the smoking male population compared with nonsmokers. There was a significant inverse gradient in the relationship between income and smoking. Single women and men were at greater risk of being smokers (odds ratio [OR], 1.9 and 2.39, respectively). Individuals from small towns (less than 50 000 inhabitants) were at significantly greater risk of smoking compared with those living in rural areas (OR, 1.45 and 1.64 in women and men, respectively). CONCLUSIONS: We found differences regarding socioeconomic characteristics and major biochemical parameters between smokers and nonsmokers in Poland. However, it is difficult to establish which associations are causal for cardiovascular risk owing to the cross­sectional design of this study.

Cost-Effectiveness of an Obesity Management Program for 6- to 15-Year-Old Children in Poland: Data from Over Three Thousand Participants.

BACKGROUND: Obesity and overweight, including childhood obesity and overweight, pose a public health challenge worldwide. According to the available research findings, long-term interventions focusing on dietary behavior, physical activity, and psychological support are the most effective in reducing obesity in children aged 6-18 years. There are limited studies showing the financial effectiveness of such interventions. OBJECTIVE: The objective of the present study was to evaluate cost-effectiveness of the 6-10-14 for Health weight management program using pharmacoeconomic indicators, i.e., cost-effectiveness analysis using the incremental cost-effectiveness ratio. METHODS: We used anthropometric data of 3,081 children included in a 1-year-long intervention with a full financial cost assessment. RESULTS: The cost of removing a child from the overweight group (BMI >85th percentile) was PLN 27,758 (EUR 6,463), and the cost of removing a child from the obese group (BMI >95th percentile) was slightly lower, i.e., PLN 23,601 (EUR 5,495). Given the obesity-related medical costs calculated in the life-long perspective, these results can be considered encouraging. At the same time, when comparing the total costs per participant with the costs of other interventions, it can be noted that they are similar to the costs of school programs containing more than 1 type of intervention. CONCLUSIONS: The 6-10-14 for Health program can be considered cost-effective. As a result of committing financial resources in the approximate amount of EUR 1,790 per child, around half of the children participating in the program have improved their weight indicators.

Development of small-molecule inhibitors of fatty acyl-AMP and fatty acyl-CoA ligases in Mycobacterium tuberculosis.

Lipid metabolism in Mycobacterium tuberculosis (Mtb) relies on 34 fatty acid adenylating enzymes (FadDs) that can be grouped into two classes: fatty acyl-CoA ligases (FACLs) involved in lipid and cholesterol catabolism and long chain fatty acyl-AMP ligases (FAALs) involved in biosynthesis of the numerous essential and virulence-conferring lipids found in Mtb. The precise biochemical roles of many FACLs remain poorly characterized while the functionally non-redundant FAALs are much better understood. Here we describe the systematic investigation of 5'-O-[N-(alkanoyl)sulfamoyl]adenosine (alkanoyl adenosine monosulfamate, alkanoyl-AMS) analogs as potential multitarget FadD inhibitors for their antitubercular activity and biochemical selectivity towards representative FAAL and FACL enzymes. We identified several potent compounds including 12-azidododecanoyl-AMS 28, 11-phenoxyundecanoyl-AMS 32, and nonyloxyacetyl-AMS 36 with minimum inhibitory concentrations (MICs) against M. tuberculosis ranging from 0.098 to 3.13 µM. Compound 32 was notable for its impressive biochemical selectivity against FAAL28 (apparent Ki = 0.7 µM) versus FACL19 (Ki > 100 µM), and uniform activity against a panel of multidrug and extensively drug-resistant TB strains with MICs ranging from 3.13 to 12.5 µM in minimal (GAST) and rich (7H9) media. The SAR analysis provided valuable insights for further optimization of 32 and also identified limitations to overcome.

Cost-Effectiveness Analysis of Integrated Care in Management of Advanced Chronic Obstructive Pulmonary Disease (COPD).

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a common disease that occurs all over the world. Models of care, initially accessed from the clinical point of view, must also be evaluated in terms of their economic effectiveness, as health care systems are limited. The Integrated Care Model (ICM) is a procedure dedicated to patients suffering from advanced COPD that offers home-oriented support from a multidisciplinary team. The main aim of the present study was to evaluate the cost-effectiveness of the ICM. MATERIAL AND METHODS We included 44 patients in the study (31 males, 13 females) with an average age 72 years (Me=71). Costs of care were estimated based on data received from public payer records and included general costs, COPD-related costs, and exacerbation-related costs. To evaluate cost-effectiveness, cost-effectiveness analysis (CEA) was used. The incremental cost-effectiveness ratio (ICER) was calculated based on changes in health care resources utilization and the value of costs observed in 2 consecutive 6-month periods before and after introducing ICM. RESULTS Costs of care of all types decreased after introducing ICM. Demand for ambulatory visits changed significantly (p=0.037) together with a substantial decrease in the number of emergency department appointments and hospitalizations (p=0.033). ICER was more profitable for integrated care than for standard care when assessing costs of avoiding negative parameters such as hospitalizations (-227 EUR), exacerbations-related hospitalizations (-312 EUR), or emergency procedures (-119 EUR). CONCLUSIONS ICM is a procedure that meets the criteria of cost-effectiveness. It allows for avoiding negative parameters such as unplanned hospitalizations with higher economic effectiveness than the standard type of care used in managing COPD.

Ocena gminnego programu ochrony zdrowia psychicznego. / Ocena gminnego programu ochrony zdrowia psychicznego.

OBJECTIVES: The aim of this article was to assess the structure of municipal Mental Health Program. METHODS: The subject of the analysis was the Gdansk Mental Health Program for the years 2016-2023. The program was verified through comparison with the model of health policy program, developed by the Agency for Health Technology Assessment and Tariff System. Particular attention was paid to the presence of all recommended components of a program and the precise definition of terminology, especially the formulated goals, expected results and efficiency measures. RESULTS: The evaluated program does not contain required components of the health policy program. Unfortunately, this affects its quality. The document reveals a lack of estimation of the program implementation costs. The main goals and specific objectives do not meet the SMART criteria. Among the measures of effectiveness included in the program, the product indicators of quantitative nature have the largest share. Additionally, there is a lack of information on how to measure quality results and determine impact indicators. Regarding the evaluation, the assessment of the quality of services, their effectiveness and durability of the intended effects were not taken into account. CONCLUSIONS: Structural recommendations for mental health programs are needed. They would increase the effectiveness of the planned activities. Such effect could be achieved by use of criteria for health policy programs expressed in the Act of 27 August 2004 on health care benefits financed from public funds. Mental health programs would benefit if they were consulted by public health specialists.

Impact of Integrated Care Model (ICM) on Direct Medical Costs in Management of Advanced Chronic Obstructive Pulmonary Disease (COPD).

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a commonly diagnosed condition in people older than 50 years of age. In advanced stage of this disease, integrated care (IC) is recommended as an optimal approach. IC allows for holistic and patient-focused care carried out at the patient's home. The aim of this study was to analyze the impact of IC on costs of care and on demand for medical services among patients included in IC. MATERIAL AND METHODS The study included 154 patients diagnosed with advanced COPD. Costs of care (general, COPD, and exacerbations-related) were evaluated for 1 year, including 6-months before and after implementing IC. The analysis included assessment of the number of medical procedures of various types before and after entering IC and changes in medical services providers. RESULTS Direct medical costs of standard care in advanced COPD were 886.78 EUR per 6 months. Costs of care of all types decreased after introducing IC. Changes in COPD and exacerbation-related costs were statistically significant (p=0.012492 and p=0.017023, respectively). Patients less frequently used medical services for respiratory system and cardiovascular diseases. Similarly, the number of hospitalizations and visits to emergency medicine departments decreased (by 40.24% and 8.5%, respectively). The number of GP visits increased after introducing IC (by 7.14%). CONCLUSIONS The high costs of care in advanced COPD indicate the need for new forms of effective care. IC caused a decrease in costs and in the number of hospitalization, with a simultaneous increase in the number of GP visits.

Factors Associated With Quitting Among Smoking Pregnant Women From Small Town and Rural Areas in Poland.

INTRODUCTION: Smoking rates among women in Poland are high, and access to specialized smoking cessation services in rural areas are limited. The aim of this study was to assess factors related to quitting among pregnant women who smoke in rural areas of Poland. METHODS: Data were collected during interviews conducted by midwives among 4512 women at various stages of their pregnancy. The interviews took place in small towns with populations having less than 8000 residents, located within 12 out of 16 voivodships (provinces). We used exhaled carbon monoxide to verify self-reported smoking status. RESULTS: Overall, 38% of women interviewed (n = 1578) smoked before they found out they were pregnant. Among these women, 33% quit just after they had become aware of their pregnancy. The main predictors of early quitting were: higher educational attainment among pregnant women (adjusted odds ratio [AOR] 3.21; 95% confidence interval [CI] = 1.81-5.68), secondary educational attainment among their partners (AOR 1.63; 95% CI = 1.06-2.48), and not having children (AOR 1.71; 95% CI = 1.31-2.24). The main barriers to early quitting were: living with at least one current smoker (AOR 0.55, 95% CI = 0.39-0.76), being single (AOR 0.45; 95% CI = 0.29-0.71), and having both parents smoke cigarettes (AOR 0.67; 95% CI = 0.46-0.97). CONCLUSIONS: A modest proportion of women included in this study quit after they became aware of their pregnancy. However, women faced multiple barriers to quitting, including the smoking status of their family members. The factors identified in the study can inform the design of tailored interventions for pregnant women in rural areas. IMPLICATIONS: Smoking rates among women in Poland are high, and access to specialized smoking cessation services in rural areas are limited. This study found that women were motivated to quit smoking, and many quit after they had become aware of their pregnancy. However, women faced multiple barriers to quitting, including the smoking status of their family members. The factors identified in the study can inform the design of tailored interventions for pregnant women in rural areas.

Wards in Opinion of Patients - A Comparative Study on the Quality of Nursing Care.

AIM: The aim of this study was to evaluate the quality of nursing care in psychiatric wards and compare it between hospitals of different types. RESULTS: Significant differences between hospitals were found in: personnel benevolence (p=0,006219) and response to patient needs (p=0,011446) as well as patients' sense of safety (p=0,020042). In both hospitals, patients were equally dissatisfied with the quality of information concerning treatment side effects (p=0,207804). In both hospitals patients were equally satisfied regarding the level of respect for their dignity and psychological support (p=0,176928). CONCLUSION: General patient perception of nursing care in psychiatry wards seems to be positive. Some tasks carried out by nurses in psychiatric care still require improvement, especially regarding providing information to patients.

Studies on novel pyridine and 2-pyridone derivatives of N-arylpiperazine as α-adrenoceptor ligands.

This paper describes the synthesis of a series of new N-arylpiperazine derivatives of pyridine and 2-pyridone. The in vitro pharmacological study indicated that all of the compounds possess affinity towards α1-adrenoceptors, with exception of 6d, and are selective over α2 receptor. The most potent compound 5f displayed 62-fold α2/α1 selectivity with Ki value of 27.3 nM for α1 receptor. Selectivity of other ligands ranged from 6 to more than 146-fold. Hydrochlorides of selected compounds with the best α1-adrenoceptor affinity (7b, 7e, 7f, 8b) were tested in vivo (hypotensive activity test in rats) and the results proved their α-adrenoreceptor antagonistic activity. Furthermore, the lipophilicity of the investigated compounds has been assessed experimentally and in silico.

Attempt to eliminate health inequalities in Poland arising at the time of political and economic transformation: Polish 400 Cities Project.

AIM: Epidemiological data show that citizens of small towns and villages have presented worse trends in cardiovascular mortality during the political, social and economic transformation in Poland during past 15 years than citizens of large towns. To try to eliminate these inequalities the Polish 400 Cities Project (P400CP), a large educational and interventional project, was prepared. The project consists of two arms: medical and social interventions. MATERIAL AND METHODS: The main aim of the medical screening intervention in P400CP is to increase detection and control of cardiovascular risk factors in inhabitants of 418 small cities (<8000 inhabitants) and surrounding villages, particularly in men and people of lower education. In 2003 and 2004 the P400CP covered 123 cities. All together, 36 696 subjects aged between 18 and 98 years were examined. In all participants, blood pressure (BP), anthropometric measurements, laboratory tests and questionnaire interviews were performed. The social arm of P400CP is one of multi-level educational intervention. Modern techniques of social psychology and marketing were involved to increase participation in interventions. RESULTS: Only 12.5% of all subjects had normal BP, cholesterol (<190 mg/dl) and glucose (<100 mg/dl in whole capillary blood) levels. During the first screening visit 65.5% of all examined subjects had BP>/=140 mmHg or >/=90 mmHg. The fasting glucose level was increased in 19% of women and 26% of men. Almost two-third of all subjects had a total cholesterol level above the norm. CONCLUSIONS: The prevalence of cardiovascular risk factors in participants of the screening programme P400CP in small towns in Poland was very high. High prevalence and low control of risk factors in participants of the P400CP confirm the decision to target this programme at citizens of small towns and villages.

Epidemiology and prevention of arterial hypertension in Poland.

The authors review the present situation in epidemiology and prevention of arterial hypertension in Poland. In 2002, the NATPOL PLUS survey on representative sample of adults (n=3051, age range 18-93) was conducted. Prevalence of hypertension, diagnosed on basis of three separate visits, was 29%, awareness 67% and efficacy of treatment 12.5%. Thus, in Poland, one-third of 8.6 million hypertensives are unaware of their disease. A comparison with data from other countries should be careful due to the different methods (age range, number of readings and visits) used in the studies. The data, in concert with a decrease in awareness of one's own blood pressure (from 71% in 1994 to 59% in 2002), called for urgent preventive measures. Two large interventions were implemented under the National Programme POLKARD in 2003: the Polish 400 Cities Project aimed to increase detection and knowledge of hypertension and other risk factors among small-town and village communities, and the educational project, A Chance for the Young Heart targeted at children aged 11-14 years and using traditional teaching methods and an interactive Internet website. Also, an educational and marketing programme targeted at public opinion leaders and decision makers (trade unions, local governments, healthcare financing authorities, print media and radio, the Polish Parliament) started in 1999 and is still in process.

[Prevention and health promotion programmes on websites of the Polish health insurance funds]. / Programy profilaktyki i promocji zdrowia prezentowane w serwisach internetowych kas chorych.

OBJECTIVE: The aim of our study was to evaluate the content and presentation of prevention and health promotion programmes on websites of the Polish health insurance funds. DESIGN: A systematic review of the content of official websites of all 17 national health insurance funds was done. RESULTS: Information on health care programmes was given on 12 websites, In four cases information can be described as sufficient and in only one case the programme was described in detail. Health insurance funds in Poland make extensive use of the Internet to communicate with contractual service providers. However, there is much to be done concerning communication with the patients.

[The role of medical university in modern prevention of cardiovascular diseases. Examples from Medical University of Gdansk]. / Rola uczelni w nowoczesnej prewencji chorób ukladu krazenia na przykladzie programów Akademii Medycznej w Gdansku.

Constant worsening of epidemiological situation in cardiovascular diseases in Poland in the 70's and 80's called for intensive measures in the field of preventive cardiology. Thus in 90's, in order to change this situation, among others, team from Department of Hypertension and Diabetology from Medical University of Gdansk started, in cooperation with other medical universities, important regional and national research programs and preventive interventions. The aim of the educational program carried out in years 1999-2001 for Members of the Polish Parliament, opinion leaders and decision makers was to increase knowledge of the Polish elites about epidemic of cardiovascular diseases in our country. These actions made possible receiving greater support from the government for new epidemiological and preventive programs in this field. Thanks to NATPOL PLUS project, carried out on the representative sample of adults in 2002, we determined for the first time the prevalence and control of main cardiovascular risk factors in Poland. Results of this program helped planning preventive tasks in the National Cardiovascular Diseases Prevention and Treatment Program POLKARD 2003-2005. The aim of the preventive programmes: SOPKARD and Polish Four-Cities Project was to work out standards of modern, comprehensive interventions. They permitted planning and introduction of the largest preventive program: the Polish 400 Cities Project (PP400M). The PP400M is addressed to citizens of all small towns (to 8000 citizens) and surrounding villages in the whole country. All these accomplishments in the field of quickly expanded clinical epidemiology and cardiovascular prevention are directed mainly to Pomeranian and Polish citizens, especially those who are not aware of high risk of myocardial infarction or stroke. The main principle of our strategy is the role of university as an expert in preparation and supervision of the programs, which were carried out by the specialized organizations and firms such as PBS in Sopot. The second important component of our strategy was an intensive cooperation with other leading research centres in Poland that allowed taking advantage of the joint achievements.

[Health situation in poviats and cities with poviats status of Pomerania voivodeship--model studies]. / Sytuacja zdrowotna w powiatach i miastach na prawach powiatu województwa pomorskiego--badania modelowe.

The results of model study on the health status estimation of poviats and cities with poviats status population of Pomeranian voivodeship based on synthetic measures are presented. The measures were the elements of multidimensional comparative analysis. In the research the health status of population was estimated thoroughly from many points of view depending on different criteria. The criteria were representing as followed: economy, demography, social welfare, ecology and health service system. The model study was based on statistical data of poviats and cities with poviats status of Pomeranian voivodeship using prepared scheme of observations. Regarding to the obtained results of synthetic measures estimation, the objects were ranked and belonging to a determined group was defined. In the last part of the research the results of model study are described.