Disparities in knowledge of cardiovascular risk factors and prevention methods related to cardiovascular status and functional health literacy in Poland, 2020-2021.

BACKGROUND: Numerous studies have reported a significant role of health literacy (HL) in the prevention or treatment of various diseases. However, in Poland, there was no scientific research involving simultaneously the status of cardiovascular disease (CVD) and HL in assessment of health knowledge; therefore, it became the objective of our study. AIMS: We aimed to evaluate the level of CVD knowledge depending on CVD status and functional HL in the Polish population. METHODS: The study population consisted of 2827 participants from the WOBASZ II Survey aged 20-89 years: 2266 were CVD-free (non-CVD), 361 were hospitalized for CVD (CVDH[+]), and 200 were diagnosed with CVD but not hospitalized (CVDH[-]). The Newest Vital Sign test (NVS) was applied to determine functional HL. Self-reported knowledge of CVD risk factors (RFs) and prevention methods (PMs) in participants with different CVD status depending on HL was estimated. Multivariable ordinal and binary logistic regression analyses were performed to find predictors of RFs and PMs knowledge. RESULTS: The knowledge of CVD RFs and/or PMs was strictly related to HL and CVD status. Inadequate HL decreased the satisfactory (≥5 RFs/PMs) knowledge of RFs (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.40-0.62) and PMs (OR, 0.56; 95% CI, 0.45-0.71). CVDH(-) participants were more likely to have satisfactory PMs knowledge (OR, 1.49; 95% CI, 1.02-2.16), while CVDH(+) participants satisfactory RFs knowledge (OR, 1.85; 95% CI, 1.35-2.53). CONCLUSIONS: HL and CVD status are the key determinants of CDV RFs/PMs knowledge. Functional HL significantly affects health knowledge; therefore, HL screening should be recommended in primary care to increase the effectiveness of primary CVD prevention.

Do physical activity interventions combining self-monitoring with other components provide an additional benefit compared with self-monitoring alone? A systematic review and meta-analysis.

OBJECTIVE: To determine the net effect of different physical activity intervention components on step counts in addition to self-monitoring. DESIGN: A systematic review with meta-analysis and meta-regression. DATA SOURCES: Five databases (PubMed, Scopus, Web of Science, ProQuest and Discus) were searched from inception to May 2022. The database search was complemented with backward and forward citation searches and search of the references from relevant systematic reviews. ELIGIBILITY CRITERIA: Randomised controlled trials comparing an intervention using self-monitoring (active control arm) with an intervention comprising the same treatment PLUS any additional component (intervention arm). DATA EXTRACTION AND SYNTHESIS: The effect measures were mean differences in daily step count. Meta-analyses were performed using random-effects models, and effect moderators were explored using univariate and multivariate meta-regression models. RESULTS: Eighty-five studies with 12 057 participants were identified, with 75 studies included in the meta-analysis at postintervention and 24 at follow-up. At postintervention, the mean difference between the intervention and active control arms was 926 steps/day (95% CI 651 to 1201). At a follow-up, the mean difference was 413 steps/day (95% CI 210 to 615). Interventions with a prescribed goal and involving human counselling, particularly via phone/video calls, were associated with a greater mean difference in the daily step count than interventions with added print materials, websites, smartphone apps or incentives. CONCLUSION: Physical activity interventions that combine self-monitoring with other components provide an additional modest yet sustained increase in step count compared with self-monitoring alone. Some forms of counselling, particularly remote phone/video counselling, outperformed other intervention components, such as websites and smartphone apps. PROSPERO REGISTERED NUMBER: CRD42020199482.

TXNIP inhibition in the treatment of diabetes. Verapamil as a novel therapeutic modality in diabetic patients.

Loss of pancreatic ß-cell is a critical factor in the pathogenesis of type 1 diabetes and it also occurs in type 2. TXNIP (thioredoxin - interacting protein), also known as vitamin D3-upregulated protein 1, or thioredoxin-binding-protein-2, regulates this process and modulates cellular redox balance. TXNIP is localized primarily in the nucleus, but under oxidative stress it moves to mitochondria, where it interacts with mitochondrial thioredoxin 2. Overexpression of TXNIP induced by hyperglycaemia is typical for diabetes and insulin resistance and leads to apoptosis of pancreatic ß-cell, cardiomyopathy, metabolic disorders and multiple harmful effects. It activates NLRP3 inflamasomme and IL-1ß, a cytokine involved in type 2 diabetes and insulin resistance. TXNIP influences peroxisome proliferator-activated receptor alpha transcriptional activity, expression of glucose transporter-1, nitric oxide production in endothelium and insulin production in ß-cells. TXNIP overexpression leads to diabetic retinopathy, nephropathy, atherosclerosis, it occurs in cancers and autoimmune diseases, while its deficiency protects ß cells. Reduction of TXNIP is an important target in diabetes treatment. In this mechanism insulin, metformin and inhibitors of dipeptydylopeptydase IV are involved. It has been observed that calcium channel blockers (CCB) used in hypertension also inhibit TXNIP expression in cardiomyocytes. L-type channels identification in pancreatic ß-cells revealed that CCB inhibit TXNIP expression also in ß-cells. For the first time, verapamil was distinguished as an agent that not only inhibits TXNIP expression in pancreatic ß-cells, but also enhances ß cell survival and function, and possibly prevents diabetes.

Work-Life Balance and Mental and Physical Health among Warsaw Specialists, Managers and Entrepreneurs.

Many studies have shown that low work-life balance (WLB) can be harmful to health. Poland is a country with one of the lowest indicators on the WLB scale among European countries but there are only a few studies about the connection between WLB and health. The present analysis aimed to answer the questions of whether the lower WLB among Warsaw's middle class correlates with poorer mental and physical health, and what life orientations and values typical of the middle class are related to work-life balance. Two surveys were conducted in the years 2003 and 2013 on the quota samples of 500 members of the Warsaw middle class: specialists, managers, and entrepreneurs. The current analysis has indicated the connection between a lower level of WLB and worse mental and physical health. Some middle-class life orientations are connected with a high WLB. The relationship between WLB and health was stronger in 2013 than in 2003. It can be considered a result of mentality and lifestyle changes and generational renewal. The study should be repeated in 2023 after the COVID-19 pandemic as the work situation of the middle class may have changed.

MLK4 regulates DNA damage response and promotes triple-negative breast cancer chemoresistance.

Chemoresistance constitutes a major challenge in the treatment of triple-negative breast cancer (TNBC). Mixed-Lineage Kinase 4 (MLK4) is frequently amplified or overexpressed in TNBC where it facilitates the aggressive growth and migratory potential of breast cancer cells. However, the functional role of MLK4 in resistance to chemotherapy has not been investigated so far. Here, we demonstrate that MLK4 promotes TNBC chemoresistance by regulating the pro-survival response to DNA-damaging therapies. We observed that MLK4 knock-down or inhibition sensitized TNBC cell lines to chemotherapeutic agents in vitro. Similarly, MLK4-deficient cells displayed enhanced sensitivity towards doxorubicin treatment in vivo. MLK4 silencing induced persistent DNA damage accumulation and apoptosis in TNBC cells upon treatment with chemotherapeutics. Using phosphoproteomic profiling and reporter assays, we demonstrated that loss of MLK4 reduced phosphorylation of key DNA damage response factors, including ATM and CHK2, and compromised DNA repair via non-homologous end-joining pathway. Moreover, our mRNA-seq analysis revealed that MLK4 is required for DNA damage-induced expression of several NF-кB-associated cytokines, which facilitate TNBC cells survival. Lastly, we found that high MLK4 expression is associated with worse overall survival of TNBC patients receiving anthracycline-based neoadjuvant chemotherapy. Collectively, these results identify a novel function of MLK4 in the regulation of DNA damage response signaling and indicate that inhibition of this kinase could be an effective strategy to overcome TNBC chemoresistance.

Influence of the recurrent syncope episodes on neurocognitive functions in patients with vasovagal syncope.

The aim of study was to evaluate an influence of recurrent syncope episodes on the neurocognitive functions (NCF) in patients with suspected VVS. AIM: The aim of study was to evaluate an influence of recurrent syncope episodes on the neurocognitive functions (NCF) in patients with suspected VVS. MATERIALS AND METHODS: Study population: 24 pts. (16 women) aged 17-70 yrs (mean age 40 years), with suspected VVS, referred to HUTT (head-up tilt test). All pts. underwent initial evaluation regarding to the number and circumstances of the syncopal and/or presyncopal spells. All pts performed HUTT with Westminster protocol. Basing on the syncope history and HUTT results, two groups of pts were distinguished: gr. I - 18 pts with at least 2 syncopal spells and positive HUTT, and gr. II 6 pts with only presyncopal status without complete loss of consciousness and negative HUTT. All pts underwent the evaluation of NCF with computer-assisted Vienna Test System battery, consisted of the following tests: DAUF - evaluation of long-term selective attention and concentration; COG - assessment of attention and concentration; STROOP - registration of the color-word interference tendency, CORSI - estimation of visual short-term memory capacity and implicite visuo-spatial learning. Values of the measured parameters were compared between both groups of pts. RESULTS: Patients without syncope (gr. II) had higher number of correctly reproduced sequences (11,0 vs 8,38 p<0,01) and Reliable Spatial Span score (5,50 vs 4,46,p<0,02) in CORSI test, in relation to pts with syncope history (gr. I). This suggests possible influence of the recurrent syncope episodes on the short-term memory capacity in pts with VVS. There were no significant differences between groups, comparing results of the other tests. CONCLUSIONS: Repeated syncope episodes may lead to impairment of short-term memory capacity in patients with vasovagal syndrome. Syncope episodes may have potentially negative influence on neurocognitive functions in patients with vasovagal syndrome.

The relationship between audience mentality and attitudes towards healthy lifestyle promotion in the mass media.

Health promoters who use the mass media to encourage people to change their health behaviours usually underestimate the importance of audience's mental predispositions, which may determine their susceptibility to such influences. This paper presents research findings that show how some elements of an audience's mentality are related to their attitudes towards healthy lifestyle promotion in the mass media (HLPMM). The research project, undertaken between 2007 and 2009, comprised: a qualitative study using in-depth interviews (N=30); a self-administered survey on a purposive sample (N=237) and a computer-assisted personal interview or interviewing (CAPI) survey on a representative sample of Polish adult population (N=934). The findings from the first two studies were used to construct a scale to investigate the attitude towards HLPMM. This scale was applied in a nation wide survey and, as a result, four dimensions of the attitude were identified: (1) appraisal of the idea of HLPMM; (2) appraisal of HLPMM practice; (3) propensity to receive media messages promoting healthy lifestyle and (4) propensity to avoid such messages. Moreover, the survey results confirmed the hypotheses whereby a higher degree of individualism, a higher degree of authoritarianism, a weaker demanding orientation and generalised trust are related to a more positive attitude towards HLPMM. The aforementioned relationships indicate that producers of media messages promoting a healthy lifestyle need to take account of their audience's mentality, since knowledge of mental predispositions of the target audience may help them make the message more suitable for specific recipients.

Mycophenolic Acid Metabolites Acyl-Glucuronide and Glucoside Affect the Occurrence of Infectious Complications and Bone Marrow Dysfunction in Liver Transplant Recipients.

BACKGROUND Mycophenolic acid (MPA) prodrugs are anti-proliferative immunosuppressive agents commonly used after organ transplantation. Although they are generally well tolerated by patients, adverse effects may occur. It is postulated that MPA metabolites could also contribute to these adverse effects. MATERIAL AND METHODS The objective of this study was the assessment of concentrations of total MPA and its metabolites, phenyl glucuronide (MPAG), acyl glucuronide (AcMPAG) and glucoside (GluMPA), using liquid chromatography combined with mass spectrometry (LC/MS/MS) in two groups: kidney transplant recipients and liver transplant patients. Associations of MPA and its metabolites with adverse effects were analyzed. RESULTS The study group consisted of 211 recipients of liver or kidney transplants who received immunosuppressive therapy, including MPA prodrugs. Multivariant analysis showed a positive influence of MPA on gastroenterotoxicity in kidney transplant recipients. In liver patients, gastroenterotoxicity was associated with lower MPAG concentrations. A positive influence of AcMPAG on bacterial infections in liver transplant patients was observed. In liver transplant recipients, a positive influence of MPA and a negative influence of GluMPA levels on the PLT count were revealed. MPA and its metabolites did not influence the hemoglobin levels in both groups. There were no significant relationships among MPA, its metabolites and WBC counts. CONCLUSIONS In kidney transplant recipients, total MPA trough concentration is associated with gastroenterotoxicity and its monitoring could have important role in management of gastrointestinal complications. The quantification of AcMPAG in liver recipients receiving MPA may be helpful in avoiding bacterial infections. GluMPA seems to have a toxic effect on thrombopoiesis.

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.

Two rapid ultra performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) methods with common sample pretreatment for therapeutic drug monitoring of immunosuppressants compared to immunoassay.

Therapeutic drug monitoring of immunosuppressive agents is a critical and essential part of patient therapy after organ transplantation. We have developed high-throughput, robust, and rapid liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) methods with common pretreatment procedures for simultaneous quantification of four immunosuppressive agents (everolimus, sirolimus, tacrolimus, and cyclosporin A) in whole blood and one immunosuppressant (mycophenolic acid) in plasma. The new approach used in this work is based on improved sample preparation procedures allowing the analysis of five immunosuppressive drugs. Whole blood was prepared by transferring 100µL of blood into a 1.5-mL silanized conical test tube. Zinc sulfate solution (150µL), containing deuterated internal standards, was added to perform hemolysis. The samples were vortexing for 10s, followed by the addition of 250µL acetonitrile, containing internal standard for cyclosporin A, to precipitate proteins. The mixture was vortexed for 1min and centrifuged for 2min at 14,000rpm. The whole supernatant was transferred to a vial. To prepare blood plasma, the hemolysis step involving the addition of zinc sulfate was omitted and, instead of acetonitrile, methanol was used as the solvent for the internal standard (mycophenolic acid-d3). The volumes of chemicals used in this procedure were the same as those used in the procedure for immunosuppressants in whole blood. The basic validation parameters for the analytical methods were limits of detection (0.5ng/mL for everolimus, sirolimus and tacrolimus, 25ng/mL for cyclosporin A and 100ng/mL for mycophenolic acid), precision (<15%), recovery (>84%), repeatability and reproducibility. Possible mutual ion suppression was eliminated in the presence of internal standards. The method developed for the quantitation of immunosuppressants in whole blood was used to analyze 276 patient samples containing tacrolimus and 55 samples containing cyclosporin A. The results from LC/MS/MS were compared to those obtained from immunoassays of the same samples. Immunoassays significantly overestimated the concentrations of immunosuppressants.

Urine proteome of autosomal dominant polycystic kidney disease patients.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is responsible for 10% of cases of the end stage renal disease. Early diagnosis, especially of potential fast progressors would be of benefit for efficient planning of therapy. Urine excreted proteome has become a promising field of the search for marker patterns of renal diseases including ADPKD. Up to now however, only the low molecular weight fraction of ADPKD proteomic fingerprint was studied. The aim of our study was to characterize the higher molecular weight fraction of urinary proteome of ADPKD population in comparison to healthy controls as a part of a general effort aiming at exhaustive characterization of human urine proteome in health and disease, preceding establishment of clinically useful disease marker panel. RESULTS: We have analyzed the protein composition of urine retentate (>10 kDa cutoff) from 30 ADPKD patients and an appropriate healthy control group by means of a gel-free relative quantitation of a set of more than 1400 proteins. We have identified an ADPKD-characteristic footprint of 155 proteins significantly up- or downrepresented in the urine of ADPKD patients. We have found changes in proteins of complement system, apolipoproteins, serpins, several growth factors in addition to known collagens and extracellular matrix components. For a subset of these proteins we have confirmed the results using an alternative analytical technique. CONCLUSIONS: Obtained results provide basis for further characterization of pathomechanism underlying the observed differences and establishing the proteomic prognostic marker panel.

Attitudes towards healthy lifestyle promotion in mass media in the Polish adult population.

BACKGROUND: Healthy lifestyle promotion in mass media is a very important way to diminish cardiovascular diseases morbidity and mortality. Effectiveness of healthy lifestyle promotion can, among others, depend on people's attitudes towards it. AIM: To characterise the Pole's attitudes towards healthy lifestyle promotion in mass media and identify their socio-demographic predictors. METHODS: A research project consisted of qualitative and quantitative studies. Qualitative research containing 30 individual in-depth interviews was carried out from June 2007 to April 2008. A survey on national Polish sample including 934 adults was conducted in November 2008. In the study there was used the scale to estimate the attitudes towards healthy lifestyle promotion in mass media containing four subscales: appraisal of the idea of healthy lifestyle promotion in mass media (regarding a need of healthy lifestyle promotion in mass media), appraisal of its practice (which means credibility as well as effectiveness manifested in the change of people's behaviour), propensity to receive messages and propensity to avoid messages promoting healthy lifestyle. RESULTS: Above 71% of Poles is characterised by a positive attitude towards healthy lifestyle promotion in mass media. As much as 87% of people positively evaluate its idea; about 70% have high propensity to receive messages promoting healthy lifestyle and only 21% is characterised by high propensity to avoid them. On the contrary, only 29% of the respondents positively evaluate the practice of healthy lifestyle promotion in mass media. The results of multivariable linear regression analysis show that being a woman and having higher education are the predictors of relatively positive attitude towards healthy lifestyle promotion in mass media while living in the biggest cities and being executives or intellectuals are related to more negative attitude. CONCLUSIONS: Results indicate the need to enhance credibility of messages promoting healthy lifestyle as well as create ones that would better reach men and low-educated people.

Adenosine as a metabolic regulator of tissue function: production of adenosine by cytoplasmic 5'-nucleotidases.

Adenosine is a product of complete dephosphorylation of adenine nucleotides which takes place in various compartments of the cell. This nucleoside is a significant signal molecule engaged in regulation of physiology and modulation of the function of numerous cell types (i.e. neurons, platelets, neutrophils, mast cells and smooth muscle cells in bronchi and vasculature, myocytes etc.). As part a of purinergic signaling system, adenosine mediates neurotransmission, conduction, secretion, vasodilation, proliferation and cell death. Most of the effects of adenosine help to protect cells and tissues during stress conditions such as ischemia or anoxia. Adenosine receptors and nucleoside transporters are targets for potential drugs in many pathophysiological situations. The adenosine-producing system in vertebrates involves a cascade dephosphorylating ATP and ending with 5'-nucleotidase (EC 3.1.3.5) localized either on the membrane or inside the cell. In this paper the cytoplasmic variants of 5'-nucleotidase are broadly characterized as well as their clinical relevance. The role of AMP-selective 5'-nucleotidase (cN-I) in the heart, skeletal muscle and brain is highlighted. cN-I action is crucial during ischemia and important for the efficacy of some nucleoside-based drugs and in the regulation of the substrate pool for nucleic acids synthesis. Inhibitors used in studying the roles of cytoplasmic and membrane-bound 5'-nucleotidases are also described.