Search

ObjectiveTo determine the net effect of different physical activity intervention components on step counts in addition to self-monitoring.DesignA systematic review with meta-analysis and meta-regression.Data sourcesFive 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 criteriaRandomised 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 synthesisThe 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.ResultsEighty-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.ConclusionPhysical 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 numberCRD42020199482.

Ma&lstrok;gorzata &Lstrok;ysek-G&lstrok;adysi&nacute;ska,1 Magdalena Starz,2 Agnieszka Borowiec-S&eogon;k,2 Iwona Sufin,2 Anna Wieczorek,1 Magdalena Chrapek,3 Dorota Zar&eogon;bska-Michaluk,4 Patrycja Sufin,2 Stanis&lstrok;aw G&lstrok;uszek,4 Wioletta Adamus-Bia&lstrok;ek4 1Institute of Biology, Jan Kochanowski University, Kielce, Poland; 2Meduniv Sp. z o.o, Kielce, Poland; 3Department of Mathematics, Jan Kochanowski University, Kielce, Poland; 4Institute of Medical Sciences, Jan Kochanowski University, Kielce, PolandCorrespondence: Wioletta Adamus-Bia&lstrok;ek, Jan Kochanowski University, Institute of Medical Sciences, IX Wieków Kielc 19a, Kielce, 25-516, Poland, Tel +48 788 860 604, Email wioletta.adamus-bialek@ujk.edu.plPurpose: The COVID-19 pandemic has been going on for almost three years, and so far, many preventive and therapeutic strategies have been developed. The issue of subsequent booster vaccinations is currently being discussed. We aimed to analyze how the third dose of vaccination against COVID-19 correlates with the dynamics of IgG anti-SARS-CoV-2 spike protein antibody levels in a group of healthy people.Patients and Methods: The prospective study included 93 participants before and after a second booster of COVID-19 vaccination, from whom 4 blood samples were collected at intervals. The levels of IgG anti-SARS-CoV-2 in serum were identified using the chemiluminescent immunoassay specific for the receptor-binding domain (RBD) of the S1 protein. The analysis of the results was performed using appropriate statistical methods, considering p < 0.05 as a statistically significant value.Results: The IgG levels were significantly higher and less diverse after the same follow-up time from the second booster vaccination compared to the first booster. The antibody levels were positively correlated with female, healthcare workers, the elderly and participants with a negative COVID-19 history. Furthermore, the increase in IgG antibodies after the second booster vaccination correlated inversely with the baseline level of antibodies before the vaccination. The latest results showed that antibody levels dropped 1.5-fold after approx. 10 months from the second booster vaccination but still remained at a protective level.Conclusion: Booster vaccinations seem to better stimulate immune memory, and in the case of borderline IgG level induces the greatest increase in antibodies. It is worth considering the individual parameters of patients and measuring antibodies before vaccination.Keywords: pandemic, virus, infection, immune response

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.

WstępWyrażanie emocji związane jest z określonym modelem prozodycznym, czyli różni się zakresem wysokości i dynamiki głosu. Celem pracy było zbadanie czynności gardła i krtani towarzyszącej okazywaniu różnych emocji.Materiał i metodaMateriał stanowiło 16 osób. Ruchy gardła i krtani były nagrywane z wykorzystaniem wideonasofiberoskopii, podczas ciągłej fonacji głoski [i] najpierw bez emocji, na różnej wysokości i głośności, a następnie podczas wyrażania emocji: gniewu, radości, strachu, smutku, zdziwienia, obrzydzenia i pogardy. Przeanalizowano 160 obrazów wideo nagranych podczas fonacji każdego zadania. Porównywano stopień kompresji przestrzeni nadgłośniowych dla fonacji z wyrażaniem emocji i bez emocji. Jednocześnie oceniano, jaka cecha głosu dominuje w każdym typie emocji.WynikiW obrazach fiberoskopowych gardła i krtani uzyskanych w przebiegu fonacji z wyrażaniem emocji stwierdzano większą kompresję niż na obrazach pochodzących z fonacji dźwięku wygodnego, bez emocji. Największy stopień kompresji gardła dolnego i przedsionka krtani stwierdzono dla obrzydzenia, pogardy i gniewu, najmniejszy dla strachu i smutku oraz radości.WnioskiCzynność toru nadgłośniowego zależy od jakości tworzonego głosu i intencji wypowiedzi.

Resistance to chemotherapy leads to high rates of relapse and poor outcomes in patients with triple-negative breast cancer (TNBC). Therefore, there is a need to identify novel molecular targets that could be exploited to overcome TNBC chemoresistance. Mixed-lineage kinase 4 (MLK4) is a member of MLK family of serine/threonine kinases. Large-scale genomic and transcriptomic data indicated that MLK4 gene (MAP3K21/KIAA1804) is amplified and overexpressed in approximately 50% of triple-negative tumors. We have recently demonstrated that MLK4 promotes the aggressive growth and metastatic potential of TNBC cells. However, the functional role of MLK4 in resistance to chemotherapy has not been investigated so far. In our recent study, we have shown that MLK4 contributes to TNBC chemoresistance by regulating the pro-survival response to DNA-damaging therapies. MLK4 knock-down or inhibition sensitized TNBC cell lines to doxorubicin and etoposide in vitro. Moreover, loss of MLK4 enhanced sensitivity of HCC1806 TNBC cell line towards doxorubicin in a xenograft mouse model. Our data indicated that MLK4 silencing induced persistent DNA damage accumulation and enhanced apoptosis in TNBC cells treated with chemotherapeutics. To further determine cellular mechanisms responsible for the identified MLK4-dependent chemoresistance in TNBC, we performed a quantitative phosphoproteomic analysis of control and MLK4-depleted HCC1806 cells, either untreated or treated with doxorubicin. We found that the doxorubicin-induced phosphorylation of several core DNA damage response components, including ATM, TRIM28 (KAP-1), MDC1 and TP53BP1, was impaired in cells with MLK4 knock-down. These findings were further confirmed using HCC1806 cells with CRISPR/Cas9-mediated deletion of MLK4, which showed markedly reduced phosphorylation of ATM kinase at Ser1981 - a site critical for ATM monomerization and activation. ATM was shown to activate NF-κB transcription in response to DNA damage through the well-established nuclear to cytoplasmic signaling pathway involving NEMO. Interestingly, we observed diminished phosphorylation of NEMO and reduced expression of several NF-кB-associated pro-survival cytokines (IL6, IL8, CXCL1, CXCL6) in MLK4-depleted TNBC cells treated with doxorubicin. These data, along with the additional immunoprecipitation and kinase assay experiments, indicate that MLK4 is involved in the regulation of DNA damage response signaling and ATM-NEMO pathway activation. Moreover, our recent results suggest that MLK4 controls autocrine/paracrine signaling loops in cancer cells and tumor microenvironment (TME) upon treatment with chemotherapy. We currently aim to further determine how MLK4-dependent crosstalk between TNBC cells and TME contributes to chemoresistance and tumor progression. Citation Format: Dawid Mehlich, Michal Lomiak, Aleksandra Sobiborowicz, Alicja Mazan, Dagmara Dymerska, Lukasz M. Szewczyk, Anna Mehlich, Agnieszka Borowiec, Monika K. Prelowska, Dominika Nowis, Anna A. Marusiak. Mixed-lineage kinase 4 is involved in the activation of the ATM-NEMO signaling axis in response to DNA damage and confers chemoresistance in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 151.

Background Self-monitoring is a cornerstone of many complex physical activity interventions and is a powerful behaviour change technique leading to substantial physical activity increases. Whether additional intervention components, such as counselling or incentives, yield further benefits over self-monitoring is not known. We aimed to determine whether complex physical activity interventions that combine self-monitoring with other intervention components provide an additional benefit to self-monitoring alone. Methods In this systematic review and meta-analysis, we searched for randomised controlled trials that compared an intervention using objective self-monitoring with an activity monitor to increase physical activity (active control group) with an intervention comprising precisely the same treatment plus any additional component intended to further increase physical activity (intervention group). An initial search (July 8, 2020) of five databases (PubMed, Scopus, Web of Science, ProQuest, Discus), limited to English language and without publication date restrictions, was complemented by backward and forward citation searches (Nov 10, 2020). The search strings combined terms related to the domain being studied (eg, “physical activity”) AND intervention of interest (eg, “pedometer”) AND terms signalling an active control group (eg, “three arms”). We did summary data meta-analyses using random-effects models, and explored effect moderators using a series of univariate and multivariate meta-regression models. We assessed the risk of bias using the Cochrane Risk of Bias tool and measured heterogeneity using I2 statistics. This study is registered with PROSPERO, number CRD42020199482. Findings 65 studies were identified, of which 58 reported data recorded directly after the intervention ended and were included in the post-intervention meta-analysis. 17 of these studies also provided outcome data after a period of follow-up after the intervention ended. Most studies were at low risk of attrition and detection bias; selection and reporting bias varied a lot between studies, but most were at high risk of performance bias due to the difficulties in blinding participants to behavioural interventions. At post-intervention (median 12 weeks [IQR 10–16]), the mean difference between the intervention and active control groups was 947 steps per day (95% CI 613–1282; I2=90%). At follow-up (median 13 weeks [IQR 10–26]), the mean difference was 439 steps per day (95% CI 180–699;I2=47%). Interventions up to 3 months (p=0·038), having a set goal (p=0·031), and with added human counselling (p=0·0034), particularly via phone or video calls (p=0·0070), were associated with a greater increase in step count than interventions longer than 3 months, without a set goal, and without a counselling component, respectively. Interpretation Physical activity interventions that combine self-monitoring with other intervention components provide an additional benefit above and beyond self-monitoring alone. As these interventions owe a substantial part of their overall effect to simple self-monitoring, future trials should assess these interventions against active control groups consisting of self-monitoring (instead of control groups assigned to no intervention) to isolate the net effect of additional components. Funding Czech Health Research Council, Ministry of Health of the Czech Republic (grant number NU21–09–00007).

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.

TWstęp: Sposób odżywiania należy do modyfikowalnych czynników ryzyka chorób i jest jednym z przedmiotów edukacji zdrowotnej. Jego zmiana może być trudna, ponieważ jedzenie nie tylko służy zaspokojeniu potrzeb fizjologicznych, lecz także jest elementem stylu życia, który definiuje się jako spójną całość obejmującą zachowania wybierane przez ludzi w zakresie, w jakim pozwala im na to ich ulokowanie w strukturze społecznej. Różne praktyki żywieniowe mogą stanowić elementy różnych stylów życia.Celem analizy była identyfikacja stylów żywieniowych Polaków oraz ich społeczno-demograficznych uwarunkowań.Materiały i metody: Dane zebrano w 2016 r. za pomocą wywiadu kwestionariuszowego bezpośredniego na ogólnopolskiej próbie reprezentatywnej (n = 1000). Wykonano analizę głównych składowych oraz analizę regresji liniowej wielokrotnej.Wyniki: Zidentyfikowano trzy style żywieniowe – „niedbały”, „prozdrowotny” i „tradycyjny”. Styl „niedbały” jest typowy dla mężczyzn, osób młodszych oraz ludzi żyjących w większych gospodarstwach domowych. Rzadziej cechują się nim specjaliści, wykonawcy wolnych zawodów i kierownicy, a także uczniowie i studenci, emeryci i renciści oraz mieszkańcy najmniejszych miast. Styl „prozdrowotny” charakteryzuje przeważnie kobiety, osoby z wykształceniem wyższym i średnim, uczniów i studentów, a także przedsiębiorców. Styl „tradycyjny” częściej cechuje osoby młodsze, mieszkające w mniejszych gospodarstwach domowych, z wykształceniem średnim i zasadniczym zawodowym, a także mieszkańców miast liczących 50 000–200 000 mieszkańców.Wnioski: Analiza wskazuje na istnienie stylów żywieniowych związanych z ulokowaniem w strukturze społecznej, co powinno być uwzględniane w edukacji zdrowotnej w zakresie żywienia.

Introduction: Poland is a country which is characterized by the process of population aging resulting in a dynamic growth of the old-age dependency ratio. Thus, along with the aging process, we can expect, both at the individual and at the societal level, the intensification of the problems related to coping with worsening health and social dependency of the growing number of the elderly. One of the most necessary action contributing to the prevention of the above-mentioned threats is the development of health literacy. Study aim: The aim of the study is to describe and analyze, in the context of the process of aging, the status, the structure and the role of health literacy among the elderly in Poland. Material and methods: The analyzed data come from the Polish part of the European Health Literacy population-based, cross-sectional survey (HLS-EU). Field work was carried out by the TNS OBOP Research Institute in July 2011. Data were collected in Polish by a standardized questionnaire, using a Computer Assisted Personal Interview (CAPI). Results and conclusions: Almost every second person in the Polish adult population aged 15+ (44,6%) had low health literacy(inadequate + problematic). First of all the oldest people aged 65+ were at risk of low health literacy. 61,3% of Poles aged 65+ had low levels of general health literacy and only 12% of excellent, in contrast to people aged 50 years and below where these percentages were 39.9% and 21.5% respectively. In the context of this unsatisfactory level of health literacy, particularly in the elderly and the intensifying process of aging in the Polish population, health literacy development should occupy a very high position on the political agenda.

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.

The aim of study was to evaluate an influence of recurrent syncope episodes on the neurocognitive functions (NCF) in patients with suspected VVS.The aim of study was to evaluate an influence of recurrent syncope episodes on the neurocognitive functions (NCF) in patients with suspected VVS.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.Patients without syncope (gr. II) had higher number of correctly reproduced sequences (11,0 vs 8,38 p0,01) and Reliable Spatial Span score (5,50 vs 4,46,p0,02) 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.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.

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.

Background 6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) are used in many autoimmune diseases and after solid-organ transplantation. Their properties are mediated by active metabolites, 6-thioguanine nucleotides (6-TGN), and 6-methylmercaptopurine (6-MMP). The most common adverse effects are myelo- and hepato-toxicity. The aim of the study was quantification of 6-TG and 6-MMP, with the use of liquid chromatography combined with tandem mass spectrometry (LC/MS/MS) in solid-organ transplant recipients. Methods In 33 patients, kidney transplant recipient (n = 25) and liver transplant recipient (n = 8) intra-erythrocyte concentrations of 6-TG and 6-MMP were measured with the use of LC/MS/MS. Results The mean concentration of 6-TG was 205.35 ± 157.62 pmol/8 × 10 8 red blood cells (RBC); median concentration of 6-MMP was 1064.1 (35.78–11,552.9) pmol/8 × 10 8 RBC. There were no correlations between 6-TG levels and peripheral blood parameters (white blood cell count, WBC; hemoglobin, Hb concentration; PLT, blood platelet count) or alanine aminotransferase activity (AlAT) activity. Relationships between 6-MMP concentrations and peripheral blood parameters (WBC, Hb, PLT) or AlAT activity have not been found. Subgroups with leukopenia, anemia, thrombocytopenia, and liver dysfunction did not differ in concentrations of 6-TG or 6-MMP. We have observed a negative correlation between daily azathioprine dose and WBC count ( r = −0.37, P = .04). Conclusions Relationships between concentrations of azathioprine metabolites and myelotoxicity or hepatotoxicity have not been confirmed. Further studies on larger groups of patients would be helpful in a more accurate understanding of the impact of azathioprine metabolites on parameters of bone marrow and liver function.

Cyclosporine (CsA) is an immunosuppressive agent whose use is associated with adverse effects, including nephrotoxicity. There are reports indicating that some CsA metabolites may contribute to these effects. This study was aimed at evaluation of CsA metabolites and correlating them with kidney function.In 62 kidney transplant recipients (41.9% women; overall mean age, 48.44 ± 11.75 years), concentrations of CsA and 4 groups of metabolites were assessed: hydroxylated (HCsA), hydroxymethylated (HMCsA), dihydroxylated (DHCsA), and trihydroxylated (THCsA). The results were normalized with the use of the metabolite-to-parent drug ratio, and results were linked with estimated glomerular filtration rate (eGFR) at 3 months before (-3M), point zero (0M), and after 3 (+3M) and 12 (+12M) months.Multivariate analysis demonstrated the negative influence of eGFR -3M on HMCsA/CsA (β = -0.266; P .05) and the negative influence of HCsA/CsA, HMCsA/CsA, DHCsA/CsA, and THCsA/CsA on eGFR +3M (β = -0.339, β = 0.396, β = -0.314, and β = -0.321, respectively; P .005) and eGFR +12M (β = -0.363, β = -0.316, β = -0.267, and β = -0.312, respectively; P .05). We did not detect such influence of CsA concentrations on eGFR +3M and +12M. The THCsA/CsA receiver operating characteristic cutoff value for prediction of improvement of kidney function at +12M was 0.143.Our results suggest that impaired function of the transplanted kidney affects the accumulation of HMCsA. It is possible that the increased metabolite (HCsA, HMCsA, DHCsA, and THCsA) to cyclosporine ratio could influence or could be a marker of cyclosporine nephrotoxicity. In this context, the most promising marker seems to be THCsA/CsA ratio, but its real significance requires further studies to determine.

Tacrolimus (Tac) is one of the most commonly used immunosuppressive drugs after solid organ transplantation. Eight Tac metabolites have been described, but their clinical importance remains unclear. The aim of this study was quantification of the 2 major Tac metabolites, 13-O-demethyl (M-I) and 15-O-demethyl (M-III), in kidney transplant recipients and to link them with parameters of kidney and liver function, peripheral blood cell counts, and infection incidence.In 81 kidney transplant recipients, concentrations of Tac, M-I, and M-III were measured with the use of liquid chromatography combined with tandem mass spectrometry (LC-MS-MS).There was a negative correlation between M-III levels and estimated glomerular filtration rate (eGFR; r = -0.244; P .05). Also, a negative correlation between M-III concentrations and red blood cell count (RBC) was found (r = -0.349; P .05). Neither concentrations of Tac nor of M-I correlated with eGFR or RBC. M-I, M-III, and Tac were not related to alanine aminotransferase activity. Significantly higher Tac and M-III concentrations in the group with all types of infections in comparison with the group without infections were observed (6.95 ± 2.09 ng/mL vs 5.73 ± 2.43 ng/mL [P = .03] and 0.27 ± 0.17 ng/mL vs 0.20 ± 0.11 ng/mL [P = .04], respectively).The results suggest that higher concentrations of M-III may have a nephrotoxic or myelotoxic effect and result in higher incidence of infections. Further studies are needed to confirm if monitoring of M-III could minimalize adverse effects such as nephrotoxicity or infections.

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.

The solid-phase synthesis and in vitro assays on the glucose-induced insulin secretion from rat pancreatic islets of Langerhans with six new chimeric peptides were performed. All the peptides were built up of the N-terminal galanin (GAL) fragment or its analogues, linked to the C-terminal portion of substance P (SP) analogues or scyliorhinin I (SCY-I) analogues. Two strong antagonists of the inhibitory effect of galanin on the glucose-induced insulin release were found: [cycloleucine4]GAL(1-13)-SP(5-11)-amide and GAL(1-13)-[L-norleucine10]SCY-I(3-10)-amide.

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.To characterise the Pole's attitudes towards healthy lifestyle promotion in mass media and identify their socio-demographic predictors.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.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.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.

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.

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.