Expression of let-7a, miR-106b and miR-29b is changed in human gastric cancer.

MicroRNA (miRNA) are small, noncoding RNA sequences that post-transcriptionally regulate the proliferation, activity and apoptosis of human gastric cancer cells by controlling various signaling cascades. Processes that involve miRNA molecules can create a specific network of interactions in a cell, and disruption of its functioning may contribute to the transformation of normal cells into cancerous cells. Aims of our survey were: 1) study the relationship between the expression of selected miRNA types (let-7a, miR-106b, miR-29b, miR-21, miR-155, miR-222) in the gastric mucosa and pathomorphological changes determined by classical histopathological methods, 2) perform in silico analysis to select target genes for selected miRNAs and to perform functional analysis of these genes. Eighty-three subjects (45 women, 38 men; mean age 39±14 years, range: 21-80 years, were examined). Among them were 18 (21.5%) patients with chronic active gastritis, 42 (50.6%) people with chronic inactive gastritis, 9 (10.8%) patients with gastric cancer and 14 (16.9%) patients without histopathological changes. The study demonstrated that mainly the expression of 3 (miR-29b, let-7a miR-106b) out of 6 selected miRNAs are significantly different depending on the site of biopsy (body of the stomach or antrum) and the group of patients. Expression of miR-106b in the antrum and body was the highest in the group of cancer patients and the lowest in patients with chronic active gastritis. The expression of let-7a differed depending on group of patients and location. The highest expression was in the body in the group with inactive gastritis and the lowest in gastric cancer. Patients with cancer had the lowest expression of miR-29b in stomach body and it was the highest in the patients with inactive gastritis in this location. Expression of miR-21 and miR-155 determinations were not statistically significant in comparison to groups or locations, and of miR-222 was not different between the groups, but only in the control group was higher in the antrum than in the body. We conclude that identification of miRNAs may represent a promising modern complementary method in the diagnosis of gastric diseases, especially cancer.

Pharmacotherapy of patients with benign prostate enlargement and storage symptoms in everyday clinical practice.

OBJECTIVE: Storage symptoms significantly deteriorate the quality of life in men with benign prostate enlargement (BPE). Muscarinic receptor antagonists (MRAs) and ß3-adrenergic receptors agonists alone, or in combination with selective α1-alpha-antagonists, are considered the most effective medicines relieving storage symptoms. The aim of this study was to analyze the pharmacotherapy of storage symptoms in men with BPE, and their compliance with the European Association of Urology (EAU) guidelines. PATIENTS AND METHODS: The survey was conducted in 2018 by 261 urologists among 24,613 men with lower urinary tract symptoms (LUTS) and BPE treated pharmacologically. Data concerning recent severity of non-neurological LUTS, storage symptoms and pharmacotherapy were collected. RESULTS: Storage symptoms were reported by 12,356 patients (50.2%) with BPE, more frequently nocturia (75.8%), than urinary urgency (57.8%) and frequency (44.3%). Patients with storage symptoms were more frequently prescribed with MRAs and mirabegron (43.1% vs. 5.0% and 2.4% vs. 0.3%, respectively; p<0.001). Of note, 54.5% of patients with storage symptoms were treated neither with MRAs, nor ß3-adrenergic receptors agonists. In the subgroup with storage symptoms, the increasing severity of LUTS accounted for more frequent prescription of MRA (2.1% vs.  29.1% vs. 42.8% in patients with mild, moderate, and severe LUTS, respectively). Decision tree analysis revealed that patients with urinary urgency and urinary frequency, as well as younger ones with urinary urgency but without urinary frequency, were more frequently prescribed with MRAs. CONCLUSIONS: Urinary urgency and frequency are associated with increased utilization of MRAs in men with BPE in everyday clinical practice. The attitude of Polish urologists toward management of persistent storage symptoms in BPE patients is in line with the EAU guidelines.

Prediction of detrusor underactivity based on non-invasive functional tests and clinical data in patients with symptoms of bladder outlet obstruction.

OBJECTIVE: Detrusor underactivity (DU) is a common but relatively under-researched bladder dysfunction. Recently, there has been renewed interest in this topic. The aim of the study was to develop a decision-making algorithm to predict the impaired detrusor contractility in patients with LUTS (lower urinary tract symptoms). PATIENTS AND METHODS: A retrospective analysis covered 96 consecutive patients (aged 63 ± 8 years) treated pharmacologically for 50 ± 37 months due to LUTS (persisting for 64 ± 41 months). Functional tests included uroflowmetry and flow cystometry. RESULTS: Weakened detrusor functioning was detected in 58 (60.4%) patients. Decision-making algorithm that included uroflowmetry, flow cystometry and clinical data, was showed to allow to diagnose impaired detrusor function with accuracy of 73% (95% CI - confidence interval: 61-83%) and specificity of 76% (95% CI: 54-90%). The positive predictive value of the classification tree graph is equal to 90% (95% CI: 78 -96%) and the negative predictive value is 50% (95% CI: 34-66%). The weakened detrusor function was more frequent in patients with: time to reach maximum flow rate higher than 13.5 s; time to reach maximum flow rate lower than 13.5 s and mean flow ratio higher than 4.5 ml/s, but time of flow longer than 44.5 s; time to reach maximum flow rate lower than 13.5 s and mean flow ratio lower than 4.5 ml/s, but time of flow longer than 52.5 s. CONCLUSIONS: The results of the uroflowmetry can be used to predict the impaired detrusor contractility in patients with LUTS.

The mechanical properties and bactericidal degradation effectiveness of tannic acid-based thin films for wound care.

The surface area is the most important aspect when considering the interactions between a material and the surrounding environment. Chitosan (CTS) and tannic acid (TA) were previously successfully tested by us to obtain thin films to serve as wound dressings or food packaging materials. However, surface properties as well as the antimicrobial activity of the material were not considered. They are important if the material is likely to find application in biomedical or food packaging application. Thereby, this study is a further investigation of chitosan/tannic acid films surface properties. The results showed that higher content of tannic acid increases the surface free energy and roughness, which is beneficial when considering the application of the materials as wound dressings. However, higher content of chitosan provides better antibacterial properties. Hence, the most optimal complex of chitosan and tannic acid for proposed application is the ratio 80/20.

Adsorption of interacting self-avoiding trails in two dimensions.

We investigate the surface adsorption transition of interacting self-avoiding square lattice trails onto a straight boundary line. The character of this adsorption transition depends on the strength of the bulk interaction, which induces a collapse transition of the trails from a swollen to a collapsed phase, separated by a critical state. If the trail is in the critical state, the universality class of the adsorption transition changes; this is known as the special adsorption point. Using flatPERM, a stochastic growth Monte Carlo algorithm, we simulate the adsorption of self-avoiding interacting trails on the square lattice using three different boundary scenarios which differ with respect to the orientation of the boundary and the type of surface interaction. We confirm the expected phase diagram, showing swollen, collapsed, and adsorbed phases in all three scenarios, and confirm universality of the normal adsorption transition at low values of the bulk interaction strength. Intriguingly, we cannot confirm universality of the special adsorption transition. We find different values for the exponents; the most likely explanation is that this is due to the presence of strong corrections to scaling at this point.

Evaluation of the effect of liposomes loaded with chlorogenic acid in treatment of 2,4,6-trinitrobenzenesulfonic acid-induced murine colitis.

Crohn's Disease (CD), one of the types of inflammatory bowel disease, poses a significant challenge to modern healthcare. This condition severely impacts patients' quality of life, and its incidence is continuously rising. Despite constant research, current treatment options are limited and largely unsuccessful and result in serious side effects, therefore new therapy alternatives are needed. Liposomal formulation provides a new hope for disease management. In our study, we characterized the anti-inflammatory activity of mesalazine (5-ASA) and chlorogenic acid (CGA) encapsulated in liposomal formulation in the animal model of CD. Liposomes were obtained by thin film hydration method and characterized in terms of suspension stability and particle size and distribution. Colitis was induced in mice by intracolonic (i.c.) administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS). The effect of treatment with liposomal suspensions of 5-ASA and CGA was evaluated macroscopically and by measuring myeloperoxidase (MPO) activity. We observed that liposome-encapsulated 5-ASA (5 mg/kg), but not CGA (20 mg/kg) attenuated colitis as evidenced by a decreased macroscopic and microscopic scores. It may be hypothesized that the composition of liposomal lipid bilayer as well as the switch in macrophage populations leading to unfavorable accumulation of anti-inflammatory agents in the cells may underly the efficiency of obtained liposomes and need to be taken into consideration in further studies on drug delivery.

Phase transitions in solvent-dependent polymer adsorption in three dimensions.

We consider the phase diagram of self-avoiding walks (SAWs) on the simple cubic lattice subject to surface and bulk interactions, modeling an adsorbing surface and variable solvent quality for a polymer in dilute solution, respectively. We simulate SAWs at specific interaction strengths to focus on locating certain transitions and their critical behavior. By collating these new results with previous results we sketch the complete phase diagram and show how the adsorption transition is affected by changing the bulk interaction strength. This expands on recent work considering how adsorption is affected by solvent quality. We demonstrate that changes in the adsorption crossover exponent coincide with phase boundaries.

Results of Transplantation of Kidneys Procured From Donors After Brain Death Aged 60 Years and Older.

OBJECTIVE: To analyze results of transplantation of kidneys procured from donors after brain death aged 60 years and older (hereafter denoted by "≥60") compared to kidneys procured from donors after brain death aged 40-59 years (hereafter denoted by "40-59") in medium-term follow-up period, and to assess factors that affect recipient and kidney graft survival. MATERIAL AND METHODS: 92 transplant recipients of kidneys procured from donors after brain death ≥60 were enrolled into the study. The control group were 363 recipients of kidneys procured from donors after brain death 40-59. RESULTS: Mean values of serum creatinine were higher in recipients of kidneys procured from donors after brain death ≥60 compared to control after 3 years: 168.2 ± 57.5 (n = 59) vs 147.9 ± 65.7 (n = 294), P < .05; and after 5 years: 196.2 ± 95.3 (n = 38) vs 157.3 ± 80.0 µmol/L (n = 211), P < .01. Restricted mean recipient survival time was 56.4 (95% confidence interval: 55.0-57.8) and 52.0 (48.0-56.1) months, P < .05; and kidney graft survival time was 51.6 (49.6-53.5) and 43.9 (39.0-48.9) months, P < .01 in recipients who received kidneys from donors after brain death 40-59 and from donors after brain death ≥60 respectively. In Cox regression, donor death due to cardiovascular disease proved to be the factor increasing risk of kidney graft loss (hazard ratio 1.553, P < .001). CONCLUSIONS: The survival and function of kidneys procured from donors after brain death ≥60 at medium-term follow-up remain worse compared to kidneys procured from donors after brain death 40-59, and the donor dependent risk factor of kidney graft loss is cardiovascular disease, which caused donor death.

Universality of crossover scaling for the adsorption transition of lattice polymers.

Recently, it has been proposed that the adsorption transition for a single polymer in dilute solution, modeled by lattice walks in three dimensions, is not universal with respect to intermonomer interactions. Moreover, it has been conjectured that key critical exponents ϕ, measuring the growth of the contacts with the surface at the adsorption point, and 1/δ, which measures the finite-size shift of the critical temperature, are not the same. However, applying standard scaling arguments the two key critical exponents should rather be identical, hence pointing to a potential breakdown of these standard scaling arguments. Both of these conjectures are in contrast to the well-studied situation in two dimensions, where there are exact results from conformal field theory: these exponents are both accepted to be 1/2 and universal. We use the flatPERM algorithm to simulate self-avoiding walks and trails on the hexagonal, square, and simple cubic lattices up to length 1024 to investigate these claims. Walks can be seen as a repulsive limit of intermonomer interaction for trails, allowing us to probe the universality of adsorption. For each lattice model we analyze several thermodynamic properties to produce different methods of estimating the critical temperature and the key exponents. We test our methodology on the two-dimensional cases, and the resulting spread in values for ϕ and 1/δ indicates that there is a systematic error which can far exceed the statistical error usually reported. We further suggest a methodology for consistent estimation of the key adsorption exponents which gives ϕ=1/δ=0.484(4) in three dimensions. Hence, we conclude that in three dimensions these critical exponents indeed differ from the mean-field value of 1/2, as had previously been calculated, but cannot find evidence that they differ from each other. Importantly, we also find no substantive evidence of any nonuniversality in the polymer adsorption transition.

Components of metabolic syndrome in relation to plasma levels of retinol binding protein 4 (RBP4) in a cohort of people aged 65 years and older.

PURPOSE: Elevated plasma concentration of retinol binding protein 4 (RBP4) has recently emerged as a potential risk factor as a component of developing metabolic syndrome (MS). Therefore, this study aimed to analyse the relationship between components of MS and concentrations of plasma RBP4 in a population of subjects 65 years and older. METHODS: The study sample consisted of 3038 (1591 male) participants of the PolSenior study, aged 65 years and older. Serum lipid profile, concentrations of RBP4, glucose, insulin, C-reactive protein, IL-6, and activity of aminotransferases were measured. Nutritional status (BMI/waist circumference) and treatment with statins and fibrates were evaluated. Glomerular filtration rate (eGFR), de Ritis ratio, and fatty liver index (FLI), as well as HOMA-IR were calculated. RESULTS: Our study revealed a strong relationship between components of MS and RBP4 in both sexes: plasma RBP4 levels were increased in men by at least 3×, and in women by at least 4×. Hypertriglyceridemia was most strongly associated with elevated plasma RBP4 levels. Multivariate, sex-adjusted regression analysis demonstrated that chronic kidney disease [OR 1.86 (95% CI 1.78-1.94)], hypertriglyceridemia [OR 1.52 (1.24-1.87)], hypertension [OR 1.15 (1.12-1.19)], low serum HDL cholesterol [OR 0.94 (0.92-0.97)], and age > 80 years [OR 0.86 (0.81-0.90)] were each independently associated with RBP4 concentration (all p < 0.001). CONCLUSIONS: In Caucasians 65 years and older, RBP4 serum levels are associated with a number of components of MS, independent of sex and kidney function. Hypertriglyceridemia as a component of MS is most significantly related to RBP4 concentration.

[Beta-adrenoceptor-mediated cyclic AMP signal in different types of cultured nerve cells in normoxic and hypoxic conditions].

ß-adrenergic neurotransmission is an important factor regulating brain activity such as neuronal and glial survival, plasticity, membrane transport or cellular metabolism. Intracellular ß-adrenergic signaling, via a stimulatory G protein (Gs), activates two major down-stream effectors, i.e., adenylyl cyclase (AC) and cAMP-dependent protein kinase A (PKA). The aim of this work was to study the ability of endogenous (adrenaline and noradrenaline) and exogenous (isoprenaline) ß-adrenergic receptor agonists to increase cAMP in different types of nerve cells. Moreover, we wanted to precisely identify the receptor isoform involved in the observed phenomenon using selective ß1-, ß2- ß3-adrenoceptor blockers. In an additional study, the negative influence of hypoxia on the AC/cAMP intracellular signaling system was tested. The study was conducted in parallel on rat primary glial (astrocytes) cultures, primary neuronal cultures, C6 glioma cells and human T98G glioma cells. The formation of [^(3)H] cAMP by agonists and antagonists was measured in [^(3)H] adenine prelabeled cells under normoxic and hypoxic conditions. The obtained results revealed that adrenaline, noradrenaline and isoprenaline strongly stimulated cAMP production in all tested cell types (with highest potency in C6 glioma cells). In glial and neuronal cells the adrenaline-evoked cAMP effect was mediated mainly by the ß1-adrenoceptor, whereas in tumor cells the effect was probably mediated by all three ß-subtype specific drugs. The AC/cAMP intracellular signaling system is affected by hypoxic conditions. Considering both physiological and therapeutic importance of ß-family receptors the present work characterized the ß-adrenoceptor-mediated cAMP signal transduction pathway in different nerve cells in normoxic and hypoxic conditions. The proposed in vitro model of hypoxic conditions may serve as a good model system to study the biological effects of endogenous catecholamines as well as potential therapeutics targeting adrenergic receptors, which are impaired during ischemia in vivo.

Long-Term Outcomes of Kidney and Simultaneous Pancreas-Kidney Transplantation in Recipients With Type 1 Diabetes Mellitus: Silesian Experience.

BACKGROUND: Kidney transplantation (KTx) markedly reduces mortality in patients with end-stage kidney disease (ESKD) caused by type 1 diabetes mellitus (T1DM). The outstanding issue is whether transplantation should be limited only to KTx, with further insulinotherapy, or combined with pancreas transplantation in patients with ESKD/T1DM. The goal of this study was to compare the results of simultaneous pancreas-kidney transplantation (SPKTx) and deceased donor KTx and to identify factors affecting patient and kidney graft survival in patients with ESKD/T1DM. METHODS: Eighty-seven deceased donor KTx and 66 SPKTx operated on in the Silesia region of Poland between 1998 and 2013 were included in the retrospective analysis. RESULTS: During the mean 6.7 ± 3.6 years of follow-up, fewer cardiovascular episodes were observed in SPKTx recipients than in KTx recipients (1.5% vs 12.6%; P < .05). Five-year patient survival (80.7% in SPKTx vs 77.5% in KTx) and kidney graft survival (66.1% in SPKTx vs 70.4% in KTx) did not differ between study groups. There were no differences in patient survival (log-rank test, P = .99) or kidney graft survival (P = .99) based on Kaplan-Meier curves. Multivariable Cox proportional hazard analysis failed to identify factors explaining patient and kidney graft survival. Five-year pancreas graft survival was 58.9%. SPKTx recipients had significantly higher estimated glomerular filtration rates during the 7-year posttransplant period and less frequently developed proteinuria (6.1% vs 23%; P < .01). CONCLUSIONS: Pancreas transplantation reduced cardiovascular risk and prevented the development of proteinuria but did not improve patient and kidney graft survival in recipients with T1DM in the 7-year follow-up period.

Physicochemical and dissolution studies of simvastatin solid dispersions with Pluronic F127.

Simvastatin (SIM) solid dispersions with Pluronic F127 (PLU) obtained by kneading and fusion methods were characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and Fourier Transform Infrared Spectroscopy (FTIR). DSC studies demonstrate that the SIM/PLU solid dispersions formed a simple eutectic phase diagram. FTIR spectroscopy and XRPD studies of obtained mixtures showed no interaction between the components in the solid state and confirmed the absence of terminal solid solutions. Intrinsic dissolution studies of solid dispersions in 0.5% sodium lauryl sulfate solution (SLS) indicated that the dissolution rate markedly increased in these solid dispersions systems compared with pure SIM. The increase in dissolution rate strongly depended on ratios of drug to carriers and selection of the method of preparations of mixtures. The solid dispersions prepared in the weight ratios of 60.0/40.0% and 69.9/30.1% w/w of SIM/PLU by the kneading method showed the highest improvement in wettability and dissolution rate of SIM. Approximately 100% of the drug was dissolved from these mixtures in comparison to 3.84% of pure simvastatin within 120 min.

The influence of Body Mass Index on chronic venous disorders therapy.

AIM: Obesity is of importance among the risk factors predisposing for chronic venous disorders (CVD). Little is known how obesity affects the management of CVD. As the data concerning the treatments of CVD in the obese are incomplete, we performed an analysis of the different CVD therapies managements with respect to body mass index and the obesity. METHODS: We analyzed 9797 CVD patients from of a previous large national CVD survey, in regard to their Body Mass Index (BMI), CVD class and CVD therapies. Among them 2213 patients presented class I, 516 class II or morbid obesity. RESULTS: BMI was significantly associated with the method of CVD therapy. Logistic regression showed that venoactive drugs are preferentially used except in class I obesity patients but also when therapy is managed by general practitioner. Logistic regression analysis showed that class II and morbid obesity is associated with more frequent prevalence of previous surgical procedures related to CVD (OR=2.62 with 95% confidence interval of [2.16-3.17]) and topical agent use, (OR=1.77, [1.38-2.25]) but with a significant decreased compliance with compression therapy (OR=0.74, [0.61 - 0.89]), regardless of the clinical course of the disease, and socio-demographic factors. While class I obesity increased the adherence with VADs. CONCLUSION: The therapy of CVD is affected by body mass index. Class II and morbid obese CVD patients are less frequently compliant with compression therapy but are willing to accept surgical procedures and the use of topical agents.

Compliance in pharmacotherapy in patients with chronic venous disorders.

AIM: The aim of this study was to evaluate the factors that limit the use of venoactive drugs (VADs), especially in patient with chronic venous disorders (CVD) noncompliant with compression therapy in a nationwide survey. METHODS: Analysis included 5134 CVD patients compliant with compression therapy and 4663 of those not accepting such method of therapy, participating in a large survey. RESULTS: Venoactive drugs (VADs) and topical agents were used significantly less frequently by patients noncompliant with compression therapy compared to the compliant population (95.2% vs. 97.7%, P<0.001 and 70.1% vs. 79.9%, P<0.001, respectively). There were also less patients on two VADs concurrently in these subgroups (14.6% vs. 24.6%, P<0.001 respectively). Logistic regression analysis confirmed that noncompliant also have decreased adherence to Ruscus aculeatus extracts (OR=0.870), micronized purified flavonoid fraction (MPFF) preparations (OR=0.886), and topical agents (OR=0.877), but not horse chestnuts seed extracts. Coexisting obesity and other chronic illnesses were among the factors that decreased the use of Ruscus aculeatus extracts and micronized purified flavonoid fraction (MPFF) preparations. The use of topical agents was reduced with age, male sex, patients with coexisting chronic illnesses, obesity and adverse to accepting compression therapy. Additionally diuretics, antiplatelet agents and low-molecular weight heparins were less frequently used in the noncompliant population. CONCLUSIONS: Patients who are not compliant with compression therapy are more frequently not adherent to pharmacological therapy. Coexisting obesity and other chronic illnesses demonstrate decrease in adherence to CVD pharmacotherapy.

Statistical analysis of differential gene expression in colorectal cancer using CLEAR-test.

CLEAR test provides a novel method of analysis by combining inference for differential expression and variability. Frozen tumor specimens from 14 (3 coded Stage I, 5 Stage II, 2 Stage III and 4 Stage IV) colon cancer patients were obtained. Archived primary tumor samples were collected at the time of surgery and normal colon mucosae (controls specimens) were also collected. The studied transcriptomes were clustered using hierarchical agglomeration with Ward's method and Tchebychev distance. The separable groups of transcriptomes were classified as high clinical stage of adenocarcinoma (HCS; stages II-IV), low clinical stage of adenocarcinoma (LCS; stages I and 3 controls), and two normal colon mucosae (controls N1 and N2). The results of the CLEAR-test algorithm in normal colon specimens and adenocarcinoma specimens with low and high clinical stage showed 50 most and 50 least significant genes. The list of differential genes (p<0.01) in normal colon specimens and adenocarcinoma specimens with low and high clinical stage presented 58 genes.

Pulling self-interacting polymers in two dimensions.

We investigate a two-dimensional problem of an isolated self-interacting end-grafted polymer, pulled by one end. In the thermodynamic limit, we find that the model has only two different phases, namely a collapsed phase and a stretched phase. We show that the phase diagram obtained by Kumar [Phys. Rev. Lett. 98, 128101 (2007)] for small systems, where differences between various statistical ensembles play an important role, differs from the phase diagram obtained here in the thermodynamic limit.

Lattice model for parallel and orthogonal beta sheets using hydrogenlike bonding.

We present results for a lattice model of polymers where the type of beta sheet formation can be controlled by different types of hydrogen bonds depending on the relative orientation of close segments of the polymer. Tuning these different interaction strengths leads to low-temperature structures with different types of orientational order. We perform simulations of this model and so present the phase diagram, ascertaining the nature of the phases and the order of the transitions between these phases.

Self-avoiding random walk with multiple site weightings and restrictions.

We introduce a new class of models for polymer collapse, given by random walks on regular lattices which are weighted according to multiple site visits. A Boltzmann weight omegal is assigned to each (l+1)-fold visited lattice site, and self-avoidance is incorporated by restricting to a maximal number K of visits to any site via setting omegal=0 for l>or=K. In this Letter we study this model on the square and simple cubic lattices for the case K=3. Moreover, we consider a variant of this model, in which we forbid immediate self-reversal of the random walk. We perform simulations for random walks up to n=1024 steps using FlatPERM, a flat histogram stochastic growth algorithm. We find evidence that the existence of a collapse transition depends sensitively on the details of the model and has an unexpected dependence on dimension.

Data management system for computer aided biophysical monitoring.

The Data Stream Management System designed to be applied in medical monitoring systems is presented. Such approach simplifies the structure of the monitoring system. Communication between management and monitoring systems is based on the formal query language. The developed theory and query language is adapted to specific requirements of the signal processing in biophysical monitoring systems.