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Objectives The objective of this study was to evaluate the association between breastfeeding duration and child neurodevelopment based on the Polish Mother and Child Cohort Study. Material and Methods The current analysis included 501 mother–child pairs. The analysis evaluating the association between the length of breastfeeding and child neurodevelopment considered the following variables: maternal age and body mass index, weight gain during pregnancy, parental level of education, marital status, socioeconomic status, child gender, birthweight, type of delivery, preterm delivery, pre- and postnatal exposure to tobacco constituents and child day care attendance. Psychomotor development was assessed in 1-year-olds on the Bayley Scales of Infant and Toddler Development . Results The length of breastfeeding correlated positively with maternal age at delivery (ρ = 0.13), maternal and paternal level of education (ρ = 0.2 and ρ = 0.14 respectively), birthweight (ρ = 0.1) and marital status (ρ = 0.16) (p < 0.05). A negative correlation between the length of breastfeeding and maternal smoking status during the first year after delivery (ρ = –0.19) and weight gain during pregnancy (r = –0.1) was observed (p < 0.05). The association between the duration of breastfeeding and child development was not statistically significant in the model with the inclusion of confounding variables. A significant association between language development and maternal level of education (p = 0.004), gender of the child (p = 0.0007) and maternal weight gain during pregnancy (p = 0.01) was found. A negative association between cognitive development and maternal salivary cotinine during pregnancy (p = 0.03) and a negative association between motor development and maternal smoking status during the first year after delivery (p = 0.007) were also found. Conclusions This study found no significant association between the duration of breastfeeding and child development after adjustment for confounders. Int J Occup Med Environ Health. 2019;32(2):175–84

Background: Despite the extensive research performed on prediction of psychosis from a Clinical High Risk for Psychosis state (CHR-P), the positive predictive value of the CHR-P designation remains unsatisfactory and further models including additional clinical and biological variables are required. Existing studies indicate that schizotypy assessed at baseline in “at-risk” individuals may be considered a predictor of transition from CHR-P to psychosis. This approach, however, is burdened with bias resulting from a possible overlap between current psychopathology and schizotypal features. No studies so far have assessed schizotypy in CHR-P from a developmental perspective. Aim: The aim of the study was to identify associations between a long-standing, parent-reported premorbid level of schizoid-schizotypal traits and the probability of psychotic transition in individuals with CHR-P. Methods: The mothers of 107 individuals diagnosed as presenting CHR-P with the use of Comprehensive Assessment of At Risk Mental States12/2006 were interviewed with the Scale for the Assessment of Premorbid Schizoid-Schizotypal Traits (PSST). Results: A high level of enduring schizotypy was found to be significantly associated with psychotic transition from CHR-P (HR: 1.78, 95% CI: 1.40–2.27, p

Objective:The predictive accuracy of the Clinical High Risk criteria for Psychosis (CHR-P) regarding the future development of the disorder remains suboptimal. It is therefore necessary to incorporate refined risk estimation tools which can be applied at the individual subject level. The aim of the study was to develop an easy-to use, short refined risk estimation tool to predict the development of psychosis in a new CHR-P cohort recruited in European country with less established early detection services.Methods:A cohort of 105 CHR-P individuals was assessed with the Comprehensive Assessment of At Risk Mental States12/2006, and then followed for a median period of 36 months (25th-75th percentile:10–59 months) for transition to psychosis. A multivariate Cox regression model predicting transition was generated with preselected clinical predictors and was internally validated with 1000 bootstrap resamples.Results:Speech disorganization and unusual thought content were selected as potential predictors of conversion on the basis of published literature. The prediction model was significant (p < 0.0001) and confirmed that both speech disorganization (HR = 1.69; 95%CI: 1.39–2.05) and unusual thought content (HR = 1.51; 95%CI: 1.27–1.80) were significantly associated with transition. The prognostic accuracy of the model was adequate (Harrell’s c- index = 0.79), even after optimism correction through internal validation procedures (Harrell’s c-index = 0.78).Conclusions:The clinical prediction model developed, and internally validated, herein to predict transition from a CHR-P to psychosis may be a promising tool for use in clinical settings. It has been incorporated into an online tool available at:https://link.konsta.com.pl/psychosis. Future external replication studies are needed.

BACKGROUND An accurate understanding of dietary supplements (DS) is a prerequisite for informed decisions regarding their intake. However, there is a need for studies on this understanding among the public based on validated research tools. OBJECTIVE This study aims to assess the knowledge about DS among Polish internet users with no medical education and to identify its determinants and design an appropriate predictive model. METHODS The study protocol was prospectively registered with a statistical analysis plan. Polish users of a web-based health service and a social networking service were administered a survey consisting of the recently developed questionnaire on knowledge about DS, the questionnaire on trust in advertising DS, the beliefs about medicines questionnaire, and several other health-related single-item measures and sociodemographic questions. The results were subjected to general linear modeling. RESULTS A total of 6273 participants were included. Of the 17 yes or no questions in the questionnaire of knowledge about DS, the mean number of correct responses was 9.0 (95% CI 8.9-9.1). Health service users performed worse than social networking users by 2.3 points (95% CI 2.1-2.5) in an analysis adjusted for potential confounders. Internet users had fewer true beliefs about DS if they presented higher trust in their advertising (adjusted β=−.37; 95% CI −.39 to −.34), used DS (adjusted β=−.14; 95% CI −.17 to −.12), experienced their positive effect (adjusted β=−.16; 95% CI −.18 to −.13), were older or younger than 35 years (adjusted β=−.14; 95% CI −.17 to −.12), expressed interest in the topic of DS (adjusted β=−.10; 95% CI −.13 to −.08), reported getting information about the products from friends (adjusted β=−.13; 95% CI −.15 to −.11), and believed that medicines are harmful (adjusted β=−.12; 95% CI −.15 to −.10). The proposed 5-predictor model could explain 31.2% of the variance in knowledge about DS. The model appeared resistant to overfitting and was able to forecast most of the observed associations. CONCLUSIONS Polish internet users with no medical education exhibit some false beliefs regarding DS. Trusting the advertising of DS appears to conflict with knowledge about them. There is an urgent need for effective web-based educational campaigns on DS and the promotion of advertising literacy. After the proposed predictive model is externally validated, it may help identify the least informed target audience. CLINICALTRIAL

In recent years, bacterial probiotic dietary supplementation has emerged as a promising way to improve cognition and to alleviate stress and anxiety; however, yeast probiotics have not been tested. The aim of the present study was to determine whether 30-day supplementation with Saccharomyces boulardii enhances academic performance under stress and affects stress markers. The trial was retrospectively registered at clinicaltrials.gov (NCT03427515). Healthy medical students were randomized to supplement their diet with Saccharomyces boulardii CNCM I-1079 or placebo before sitting for an academic examination, which served as a model of stress. The grades of a final examination adjusted to subject knowledge tested in non-stressful conditions was used as a primary outcome measure. Psychometrically evaluated state anxiety, cortisol and metanephrine salivary levels, and pulse rate were tested at a non-stressful time point before the intervention as well as just before the stressor. Fifty enrolled participants (22.6 ± 1.4 years of age, 19 males) completed the trial in the Saccharomyces and placebo arms. Supplementation with Saccharomyces did not significantly modify examination performance or increase in state anxiety, salivary cortisol, and metanephrine. However, the intervention resulted in higher increase in pulse rate under stress as compared to placebo by 10.4 (95% CI 4.2–16.6) min−1 (p = 0.0018), and the effect positively correlated with increase in salivary metanephrine (Pearson’s r = 0.35, 95% CI 0.09–0.58, p = 0.012). An intention-to-treat analysis was in line with the per-protocol one. In conclusion, supplementation with Saccharomyces boulardii CNCM I-1079 appears largely ineffective in improving academic performance under stress and in alleviating some stress markers, but it seems to increase pulse rate under stress, which may hypothetically reflect enhanced sympathoadrenal activity.

Objective Existing knowledge of the relationship between olfactory identification (OI) ability and clinical risk of psychosis is inconsistent. To address this inconsistency, the aim of the present study was to identify the relationship between OI ability, with regard to the hedonic attributes of odors, and the risk of transition to psychosis in individuals with an ARMS. Methods A group of 81 individuals meeting the ARMS criteria according to the Comprehensive Assessment of At Risk Mental State were at baseline administered with the University of Pennsylvania Smell Identification Test. The hedonic attributes of odorants were normatively established. Participants were followed up for transition to psychosis for a mean period of 36.1 months (SD:27.5 months). Results The presence of deficits in the identification of pleasant odors was found to be a risk factor for conversion from an ARMS to schizophrenia. The hazard ratio for each point in deficit scores in the Cox regression model was 1.455 (95% CI: 1.211–1.747), p Significant deficits in the identification of pleasant odors were associated with a risk for conversion at both early and late time points from baseline. Conclusions The findings imply that the impaired identification of pleasant odorants may be a risk factor for the transition of an ARMS into a psychotic disorder, and highlights the need for further research of OI in “at-risk” cohorts, taking into account the hedonic attributes of odors.

Background The Beliefs about Medicines Questionnaire (BMQ) is the leading tool intended to assess the cognitive representation of medication, however, the validated Polish version of the questionnaire is lacking. Aims To adapt the original BMQ tool to the Polish language (BMQ-PL) and to validate it. Materials and methods The BMQ was adapted to Polish according to widely accepted guidelines. A total of 311 cardiovascular in- and outpatients as well as medical students taking chronic medication were surveyed to assess data-to-model fit and internal consistency of the measure. The criterion-related validity was determined with the use of Polish version of the Adherence to Refills and Medications Scale. Confirmatory and exploratory factor analyses were used, as well as general linear modeling. Results The BMQ-PL exhibited the same factorial structure as the original questionnaire and all the items loaded on their expected factors. Internal consistency of the questionnaire was satisfactory in the group of cardiovascular patients (Cronbach's alpha ranging from 0.64 to 0.82 and McDonald's omega from 0.90 to 0.91). There were significant correlations in the predicted directions between all BMQ-PL subscales and the measure of drug adherence in cardiovascular outpatients, but not in inpatients. Medical students may conceptualize the beliefs about medicines in a different way; as a result, a modified version of the BMQ-PL-General, suitable for medically-educated people, was proposed. Conclusion The BMQ-PL exhibits satisfactory proof of validity to be used among cardiovascular patients.

Background: Development of noninvasive biomarkers could potentially contribute to extending the 5-year overall survival rate of nonsmall cell lung cancer (NSCLC) patients. Circulating microRNAs (mi...

Background An accurate understanding of dietary supplements (DS) is a prerequisite for informed decisions regarding their intake. However, there is a need for studies on this understanding among the public based on validated research tools. Objective This study aims to assess the knowledge about DS among Polish internet users with no medical education and to identify its determinants and design an appropriate predictive model. Methods The study protocol was prospectively registered with a statistical analysis plan. Polish users of a web-based health service and a social networking service were administered a survey consisting of the recently developed questionnaire on knowledge about DS, the questionnaire on trust in advertising DS, the beliefs about medicines questionnaire, and several other health-related single-item measures and sociodemographic questions. The results were subjected to general linear modeling. Results A total of 6273 participants were included. Of the 17 yes or no questions in the questionnaire of knowledge about DS, the mean number of correct responses was 9.0 (95% CI 8.9-9.1). Health service users performed worse than social networking users by 2.3 points (95% CI 2.1-2.5) in an analysis adjusted for potential confounders. Internet users had fewer true beliefs about DS if they presented higher trust in their advertising (adjusted β=−.37; 95% CI −.39 to −.34), used DS (adjusted β=−.14; 95% CI −.17 to −.12), experienced their positive effect (adjusted β=−.16; 95% CI −.18 to −.13), were older or younger than 35 years (adjusted β=−.14; 95% CI −.17 to −.12), expressed interest in the topic of DS (adjusted β=−.10; 95% CI −.13 to −.08), reported getting information about the products from friends (adjusted β=−.13; 95% CI −.15 to −.11), and believed that medicines are harmful (adjusted β=−.12; 95% CI −.15 to −.10). The proposed 5-predictor model could explain 31.2% of the variance in knowledge about DS. The model appeared resistant to overfitting and was able to forecast most of the observed associations. Conclusions Polish internet users with no medical education exhibit some false beliefs regarding DS. Trusting the advertising of DS appears to conflict with knowledge about them. There is an urgent need for effective web-based educational campaigns on DS and the promotion of advertising literacy. After the proposed predictive model is externally validated, it may help identify the least informed target audience.

Background: There is barely any evidence of antipsychotic drugs affecting the molecular clockwork in human, yet it is suggested that clock genes are associated with dopaminergic transmission, i.e. the main target of this therapeutics. We decided to verify if haloperidol and olanzapine affect expression of CLOCK, BMAL1, PER1 and CRY1 in a human central nervous system cell line model. Methods: U-87MG human glioblastoma cell line was used as an experimental model. The cells were incubated with or without haloperidol and olanzapine in the concentration of 5 and 20 μM for 24 h. Real-time quantitative polymerase chain reaction with the ΔCT analysis was used to examine the effect of haloperidol and olanzapine on the mRNA expression of the genes. Results: At 5 μM, haloperidol decreased expression of CRY1 almost 20-fold. There was nearly a 1.5-fold increase in expression of PER1. Considering the 20 μM haloperidol concentration and both olanzapine concentrations, no other statistically significant effect wa...

Aim The aim of this study is to present sociodemographic and clinical characteristics of Polish individuals with an at-risk mental state (ARMS). Methods A group of 99 individuals meeting the ARMS criteria were assessed in terms of sociodemographic data, psychopathological symptoms, psychosocial functioning and comorbidity. Results The sample (mean age 19 years) was 54.55% women. At baseline, nearly 73% of the sample was educated, and 20.20% were employed. Approximately 87.88% of the participants lived with their families. Nearly 77% of the sample presented attenuated psychotic symptoms (APS), 17.17% demonstrated APS with accompanying vulnerability traits and 19.19% showed vulnerability features only. The mean Social and Occupational Functioning Assessment Scale score was 49.55 (±7.70). No effect of age, gender or level of functioning on psychopathological symptoms was observed. The most common comorbid diagnoses were depressive (44.44%) and anxiety disorders (19.19%), which coexisted in 5.05% of the individuals. Approximately 28.28% of the diagnoses met the criteria for personality disorders. The dropout rate from the study was 19.09%, with stigma as the most common reason. Conclusions Polish ARMS individuals are help-seeking young people most commonly presenting APS or vulnerability features. Despite a high level of psychosocial dysfunction, these individuals remain educationally active. Most individuals showed comorbid diagnoses (commonly depressive or anxiety disorders). Despite some differences resulting from the socioeconomic situation of the country or the specificity of the mental health services, the characteristics of the sample remain consistent with descriptions of ARMS populations worldwide. This study reaffirms the need for organizing early intervention services in non-stigmatizing settings.

In recent years, bacterial probiotic dietary supplementation has emerged as a promising way to improve cognition and to alleviate stress and anxiety, however, yeast probiotics have not been tested. The aim of the present study was to determine whether 30-day supplementation with Saccharomyces boulardii enhances academic performance under stress and affects stress markers. The trial was retrospectively registered at clinicaltrials.gov (NCT03427515). Healthy medical students were randomized to supplement their diet with Saccharomyces boulardii CNCM I-1079 or placebo before sitting for an academic examination, which served as a model of stress. The grades of a final examination adjusted to subject knowledge tested in non-stressful conditions was used as a primary outcome measure. Psychometrically evaluated state anxiety, cortisol and metanephrine salivary levels, and pulse rate were tested at a non-stressful time point before the intervention as well as just before the stressor. Fifty enrolled participants (22.6 &plusmn, 1.4 years of age, 19 males) completed the trial in the Saccharomyces and placebo arms. Supplementation with Saccharomyces did not significantly modify examination performance or increase in state anxiety, salivary cortisol, and metanephrine. However, the intervention resulted in higher increase in pulse rate under stress as compared to placebo by 10.4 (95% CI 4.2&ndash, 16.6) min&minus, 1 (p = 0.0018), and the effect positively correlated with increase in salivary metanephrine (Pearson&rsquo, s r = 0.35, 95% CI 0.09&ndash, 0.58, p = 0.012). An intention-to-treat analysis was in line with the per-protocol one. In conclusion, supplementation with Saccharomyces boulardii CNCM I-1079 appears largely ineffective in improving academic performance under stress and in alleviating some stress markers, but it seems to increase pulse rate under stress, which may hypothetically reflect enhanced sympathoadrenal activity.

Introduction Metabolic dysregulation has been recognized as a prognostic marker in idiopathic pulmonary arterial hypertension (IPAH). Objectives We aimed to investigate the association between cardiometabolic risk factors and vascular reactivity of pulmonary arteries in patients with IPAH. Patients and methods Between June 2009 and January 2015, we recruited 66 consecutive patients with IPAH. We assessed main cardiometabolic risk factors, inflammatory markers, and markers of IPAH severity. Hemodynamic evaluation included pulmonary vasoreactivity testing with the use of inhaled nitric oxide. Reduced mean pulmonary artery pressure was considered a marker of acute vasoreactivity. Acute responders were treated with calcium channel blockers and classified as long‑term responders if they had sustained vasoreactivity (near‑normal hemodynamics and World Health Organization functional class I or II) for at least 1 year. Results Thirteen patients (19.7%) showed a positive response to acute pulmonary vasoreactivity testing; however, only 9 (13.6%) remained vasoreactive at follow‑up. Machine‑learning algorithms indicated 4 variables associated with acute vasoreactivity of pulmonary arteries: high‑density lipoprotein cholesterol (HDL‑C), right atrial pressure, cardiac index, and creatinine level, and 4 predictors of long‑term vasoreactivity: HDL‑C, 6‑minute walking distance, creatinine level, and high‑sensitive C‑reactive protein level. Conclusions HDL‑C level is associated with pulmonary vasoreactivity in acute testing and predicts long‑term responsiveness to calcium channel blockers in patients with IPAH.

Table S1. Haplotype of rs6495308 with lead SNPs of bin 1 (rs16969968, G > A) or bin 2 (rs1948, G > A) in European population (1000 Genomes project). Table S2. Effect size and p value for single SNPs and for rs16969968 in combination with the three regulatory lead SNPs in nicotine dependence. Table S3. Diplotypes and their frequency generated from (SAGE and Smoking Cessation dataset). Table S4. The ORs and confidence intervals of nicotine dependence with rs16969968 allele alone (G > A) and haplotype and diplotype comprised of rs880395 (G > A), rs16969968 (G > A), rs1948 (G > A) and rs4887074 (C > G). Table S5. 5-SNP (rs880395_rs16969968_1948_rs4887074_rs6495308) haplotypes distribution of European population from 1000 Genomes Project. Figure S1. Posterior probabilities of haplotypes assigned to each subject of GWAS dataset, estimated with the Expectation Maximization (EM) algorithm. Figure S2. Machine learning analysis comparing the prediction rate (AUC) of only covariates (sex and age) vs. 1 SNP vs. 3 SNPs vs. 4 SNPs models associated with nicotine dependence. (DOCX 257 kb)

Background Although an immense effort has been made to develop novel diagnostic methods and treatment strategies for non-small cell lung cancer (NSCLC), the survival rate of this disease has remained virtually unchanged. Small non-coding RNAs called microRNAs (miRNAs) have appeared to be very promising biomarkers of cancer including NSCLC. Objective We investigated the expression level of six miRNAs, and subsequently we evaluated their diagnostic ability and their clinical significance. Methods We performed an analysis in 50 paired cancer and non-cancerous lung tissue samples collected from NSCLC patients. The RT-qPCR technique was used to investigate the expression profile. Results Obtained results indicate that miR-30a-5p, miR-126-3p and miR-486-5p are downregulated, while miR-205-5p and miR-210-3p are upregulated in NSCLC tissue. Moreover, performed stepwise discriminant analysis determined the model including miR-30a-5p and miR-210-3p which tested on the test set (n= 30) revealed an AUC of 0.969 and provided 100% sensitivity and 80% specificity in discriminating NSCLC tissue from non-cancerous lung tissue. Conclusions The present preliminary study demonstrated that five tested miRNAs were deregulated in cancer tissue. Moreover, miR-30a-5p together with miR-210-3p with excellent sensitivity and acceptable specificity may distinguish cancer tissue form non-cancerous tissue and thus may become a potential diagnostic biomarker for NSCLC.

Background/aims Catalytic subunit delta of phosphoinositide 3-kinase, p110δ, encoded by the PIK3CD gene, was recently proposed as a target for pharmacological treatment of schizophrenia. Current antipsychotic drugs were found to decrease the mRNA expression of PIK3CD , but the mechanism of this process is not known. The aim of the study was to elucidate the mechanism by which antipsychotic drugs affect the mRNA expression of PIK3CD . Methods The direct effect of haloperidol, clozapine, olanzapine, quetiapine and amisulpride on p110δ enzymatic activity was tested with a kinase assay, and the results were referenced against data on the mRNA expression of PIK3CD . Results Haloperidol, clozapine, olanzapine and quetiapine, but not amisulpride, at the concentration of 20–80 μM, were found to significantly increase enzymatic activity of p110δ by up to two times in a dose-dependent manner. Linear regression analysis revealed that more than 40% of the variance in antipsychotic drugs-induced changes in the expression of PIK3CD mRNA was explained only by changes in antipsychotic drug-regulated p110δ enzymatic activity ( p = 0.011). Conclusions Antipsychotic drugs differentially increase the enzymatic activity of p110δ. This effect is associated with that of mRNA expression of the PIK3CD gene. Drug-enzyme interaction may explain the effect of antipsychotic drugs on the expression of PIK3CD mRNA, however, further studies are needed to investigate this hypothesis.

Metabolic syndrome is a very serious health issue, not only from internal medicine's point of view. Patients suffering from overweight, arterial hypertension, lipids and carbohydrates metabolism disorders are also in the circle of interest of other areas of medicine, including psychiatry. Currently, one of key problems of pharmacotherapy is a comorbidity of metabolic syndrome and mental disorder. Depression is more common than schizophrenia. Despite the fact that in everyday clinical practice there are more patients with depression than schizophrenia, there is a bigger interest among scientists for metabolic syndrome after antipsychotic drugs than as an effect of use of antidepressant agents.The aim of an analysis was to review literature committed to influence of depression pharmacotherapy on development of metabolic syndrome. 169 results were provided, including 18 original publications. Final analysis consists of 9 that investigate correlation between antidepressive medicines use and metabolic syndrome development (but not its each individual component).In general, antidepressant pharmacotherapy is associated not only with increased risk of metabolic syndrome occurrence but also their worsening. However, it needs to be emphasized that there is a difference between antidepressants groups - tricyclic antidepressive medicines are the most commonly associated with risk of developing metabolic disorders, but also SNRIs and SSRIs are mentioned as significant contributors. Mechanisms of aforementioned changes are still unclear. However, their influence on histamine and serotonin pathways, which take part in regulation of i.e. food intake, is suggested. The search for mechanisms that are precisely responsible for metabolic changes continues, in hope of finding a way to avoid adverse effects of antidepressant medicines use.

Clinical criteria for diagnosing Clinical High Risk for psychosis are now available. However, an understanding of the factors modulating the risk of subsequent development of frank psychosis in "at risk" individuals remains elusive. The aim of the study was to identify associations between obstetric history and the development of psychotic disorders in individuals with an At Risk Mental State (ARMS).Obstetric data was obtained from the medical records of 82 individuals meeting ARMS criteria. The participants were followed up for a mean period of 42.3 (±28.3) months for transition to psychosis.A history of at least one obstetric complication (OC) endorsed as definite on the Lewis and Murray Obstetric Complications Scale was found to be associated with increased risk of transition to schizophrenia (OR: 6.57, 95% CI:1.89-22.85). The number of definite OCs was found to be positively correlated with the proportion of converters (p0.0001). The probability of conversion to schizophrenia was found to increase with a decrease of Apgar-1 and Apgar-5 scores (ORs: 0.40, 95% CI:0.22-0.74 and 0.25, 95% CI:0.10-0.63, respectively).The findings emphasise the potential value of including obstetric data in algorithms estimating the likelihood of transition of an ARMS to full-blown psychosis.

Aim of the study Hyaluronan (HA) is an extracellular matrix (ECM) polymer that may contribute to the emergence of anti-cancer drug resistance. Attempts to reverse drug resistance using small hyaluronan oligomers (oHA) are being made. The initial reports suggest that the oHA fraction may effectively reverse anti-cancer drug resistance in glioma models. However, the reversal effects of oHA of defined molecular length on glioma cells have not been investigated yet. In this study, we examined HA fragments containing 2 disaccharide units (oHA-2), 5 disaccharide units (oHA-5), and 68 kDa hyaluronan polymer (HA-68k) as agents possibly reversing the resistance of a C6 rat glioma cell line to temozolomide (TMZ) and carmustine (BCNU). Material and methods A 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) viability assay was used to assess the cytotoxicity of TMZ and BCNU in the presence or absence of the hyaluronan fragments. By comparing viability of the cells, the reversal effects of HA fragments on TMZ and BCNU resistance in C6 glioma cells were assessed. Results We found statistically significant decreases in the viability of cells in the presence of TMZ+oHA-5 as compared to TMZ alone (51.2 ±4.5 vs. 74.2 ±5.8, p = 0.0031), BCNU+o-HA5 as compared to BCNU alone (49.3 ±4.4 vs. 65.6 ±5.7, p = 0.0119), and BCNU+HA-68k as compared to BCNU alone (55.2 ±2.3 vs. 65.6 ±5.7, p = 0.0496). Conclusions Conclusions: Hyaluronan oligomers of 5 disaccharide units (oHA-5) significantly reversed the resistance of C6 cells to TMZ and BCNU. The results are only preliminary and a more thorough follow-up investigation is required to assess their actual role.

Lyme disease is one of the most known tick borne diseases in Poland caused by spirochetes of the genus Borrelia burgdorferi. Most cases of Lyme disease are diagnosed in the northeastern Poland and the south of Poland, in Śląskie, Małopolskie, Podkarpackie voivodeship. The aim of the study was to evaluate epidemiological data of Lyme disease in Małopolskie voivodeship and other voivodeships in Poland and frequency analysis of the Lyme disease as an occupational disease.The authors analyzed prevalence from 1998 to 2014. Incidence of the Lyme disease was evaluated through review data from „Choroby zakaźne i zatrucia” Bulletin and Lyme disease as an occupational disease obtained data from the Nofer Institute of Occupational Medicine in Łódź.It is estimated that the number of Lyme disease cases in Poland increased 18 times between 1998 and 2014 year (2,0 to 36 per 100,000 population), in the same period it was over 35 times of sudden rise in Lyme disease incidence in Małopolskie voivodeship. In years 2005-2014 the number of cases of Lyme disease as an occupational disease fluctuated with a slight upward trend both in Poland and Małopolskie voivoideship.In Poland number of reported cases is systematically increasing. Podlaskie and Warmińsko- Mazurskie voivodeships are areas of high prevalence. Exponential increase in the number of cases is observed in southern Poland, especially in Małopolskie voivodeship from 2013.

In modern molecular biology one of the standard ways of analyzing a vertebrate immune system is to sequence and compare the counts of specific antigen receptor clones (either immunoglobulins or T-cell receptors) derived from various tissues under different experimental or clinical conditions. The resulting statistical challenges are difficult and do not fit readily into the standard statistical framework of contingency tables primarily due to the serious under-sampling of the receptor populations. This under-sampling is caused, on one hand, by the extreme diversity of antigen receptor repertoires maintained by the immune system and, on the other, by the high cost and labor intensity of the receptor data collection process. In most of the recent immunological literature the differences across antigen receptor populations are examined via non-parametric statistical measures of the species overlap and diversity borrowed from ecological studies. While this approach is robust in a wide range of situations, it seems to provide little insight into the underlying clonal size distribution and the overall mechanism differentiating the receptor populations. As a possible alternative, the current paper presents a parametric method that adjusts for the data under-sampling as well as provides a unifying approach to a simultaneous comparison of multiple receptor groups by means of the modern statistical tools of unsupervised learning. The parametric model is based on a flexible multivariate Poisson-lognormal distribution and is seen to be a natural generalization of the univariate Poisson-lognormal models used in the ecological studies of biodiversity patterns. The procedure for evaluating a model’s fit is described along with the public domain software developed to perform the necessary diagnostics. The model-driven analysis is seen to compare favorably vis a vis traditional methods when applied to the data from T-cell receptors in transgenic mice populations.

Background/Aims: The PIK3CD gene encodes the delta catalytic subunit of phosphoinositide 3-kinase (PI3K), an element of the neuregulin 1-downstream ErbB4-PI3K signaling pathway, which was recently identified as a molecular target for the treatment of schizophrenia. The aim of the study was to examine the effect of haloperidol (HALO), clozapine (CLO), olanzapine (OLA), quetiapine (QUE) and amisulpride (AMI) on the mRNA and protein expression of genes encoding the elements of ErbB4-PI3K pathway, in a human central nervous system cell line. Methods: The U-87MG human glioblastoma cell line was used as an experimental model. Quantitative polymerase chain reaction was used to examine the expression of mRNA and enzyme-linked immunosorbent assay for protein expression. Results: At concentrations reached in clinical settings in the brain, CLO, as well as OLA and QUE to a lesser extent, but not AMI and probably not HALO, decreased the mRNA expression of PIK3CD. Protein expression of the gene did not confirm the mRNA expression profile. Conclusions: The tested antipsychotic drugs (APDs) in the U-87MG glioblastoma cell line differentially regulates the mRNA expression of PIK3CD; however, the protein expression does not confirm these findings. The results of the study may help deepen the understanding of the mechanism of action of APDs.

Healthcare centers undertake supervisory activities to control health care-associated infections (HCAIs) by elaborating procedures, identifying alert microorganisms and analyzing data collected. The aim of the study was to analyze the prevalence of alert microorganisms in hospital wards in 2010-2012.Legislation which is in force since several years introduced the principles of health care-associated infections control and reporting system. Analysis was based on annual reports on alert microorganisms provided by 19 District Sanitary and Epidemiological Stations from Małopolskie province. The data discuss positive tests results for alert microorganisms in patients who stayed in hospitals supervised by the Sanitary and Epidemiological Stations.Compared to 2010-2011, the number of tests per hospital bed in 2012 was lower, amounting to 24 (2010 - 44, 2011 - 34). Of these tests, the majority was performed in the following wards: transplantology (2010 - 339, 2011 - 354, 2012 - 330), burn care (2010 - 354, 2011 - 148, 2012 - 113) and ICUs for adults (2010 - 155, 2011 - 157, 2012 - 140). In 2010-2012, an increase in the number of positive test results for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL+) and Clostridium difficile as well as slight decrease in the number of positive test results for other alert microorganisms were noted. The highest number of microorganisms was identified in neonatal and neonatal pathology (Enterobacteriaceae ESBL+); pediatric and infectious diseases (Rotavirus); infectious diseases (Rotavirus, C.difficile); burn care (Acinetobacter baumanii, Pseudomonas sp.) and ophthalmic and hemodialysis wards (MRSA).Irrespective of a decrease in the number of tests per hospital bed in 2012, a high number of positive test results for alert microorganisms was observed. It suggests the necessity for wider application of collected data as to improve monitoring of infections and reduce resulting threats.

The understanding of the role of hyaluronan in physiology and various pathological conditions has changed since the complex nature of its synthesis, degradation and interactions with diverse binding proteins was revealed. Initially perceived only as an inert component of connective tissue, it is now known to be involved in multiple signaling pathways, including those involved in cancer pathogenesis and progression. Hyaluronan presents a mixture of various length polymer molecules from finely fragmented oligosaccharides, polymers intermediate in size, to huge aggregates of high molecular weight hyaluronan. While large molecules promote tissue integrity and quiescence, the generation of breakdown products enhances signaling transduction, contributing to the pro-oncogenic behavior of cancer cells. Low molecular weight hyaluronan has well-established angiogenic properties, while the smallest hyaluronan oligomers may counteract tumor development. These equivocal properties make the role of hyaluronan in cancer biology very complex. This review surveys recent data on hyaluronan biosynthesis, metabolism, and interactions with its binding proteins called hyaladherins (CD44, RHAMM), providing themolecular background underlying its differentiated biological activity. In particular, the article critically presents current ideas on actual role of hyaluronan in cancer. The paper additionally maps a path towards promising novel anti-cancer therapeutics which target hyaluronan metabolic enzymes and hyaladherins, and constitute hyaluronan-based drug delivery systems.