IGC investigation of the effect of the length of the n-alkyl substituent in 5-alkylsubstituted norbornenes on solute retention.

Polymerization of 5-n-alkyl-substituted 2-norbornenes synthesized a series of polymers having the same structure of the main polymer chain, but differing in the length of the alkyl substituent (up to 14 methylene units). The obtained polymers were studied by the capillary IGC method as a stationary phase during separation of a mixture of normal hydrocarbons C6-C10. Retention data in the form of a logarithm of the retention factor lnk were correlated with the size of the sorbate (via the carbon number of the alkane ZS) and with the size of the n-alkyl substituent in the polymer chain (via the carbon number of the polymer ZP). Correlation of lnk vs. ZS turned out to be linear for all polymers, but the angle of the slope of linear dependence dlnk/dZS increases with a decrease in the carbon number of the polymer ZP. Dependency of dlnk/dZS vs. ZP is not linear and indicates an increase in the retention of sorbates by the stationary phase with a decrease in the length of the alkyl substituent in the polymer chain. The correlation of the retention of lnk analytes with the carbon number of the polymer ZP is not linear and indicates an increase in the sorbate/sorbent interaction with a decrease in the length of the alkyl substituent. Inflection points were found at both correlations with ZP in the region of ZP = 8, which indicates a possible change in the sorption mechanism or a change in the phase state of the polymer. In polymer chemistry, the phase state of a polymer is characterized by the glass transition temperature Tg, the dependence of which vs. ZP turned out to be nonlinear with an inflection point at ZP ∼11. Thus, a decrease in the length of the alkyl substituent leads to the transition of the polymer from a rubbery state to a glassy one at ZP ∼ 11, which in turn, with a further decrease in the carbon number of the polymer to ZP ∼ 8, causes a change in the sorption mechanism from bulk sorption to surface sorption. The change in the sorption mechanism is accompanied by an increase in the interaction of the sorbate with the stationary phase, which manifests itself both in an increase in the retention time of analytes and in an increase in the enthalpy and entropy of sorption. The reason for this increase can be seen in the formation of a microporous structure in 5-alkyl-substituted polynorbornenes in a glassy state.

Synthesis and evaluation of druglike parameters via in silico techniques for a series of heterocyclic monosquarate-amide derivatives as potential carboxylic acid bioisosteres.

Herein, we present a synthetic compound library comprising of 13 structurally diverse heterocyclic monosquarate-amide derivatives. The compounds featured in this library were designed as potential bioisosteric replacements carboxylic acid moiety's. A good selection of the compounds presented exhibit unique molecular architecture and have shown promising results following in silico evaluation of 'druglike properties' using Swiss ADME. The research presented in this work focuses on the preparation of derivatives of 3,4-dihydroxycyclobut-3-ene-1,2-dione, a known carboxylic acid bioisostere.

A single-arm, multicenter, phase II trial of osimertinib in patients with epidermal growth factor receptor exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations.

BACKGROUND: For patients with stage IV non-small-cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions and exon 21 L858R mutations, osimertinib is the standard of care. Investigating the activity and safety of osimertinib in patients with EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations is of clinical interest. PATIENTS AND METHODS: Patients with stage IV non-small-cell lung cancer with confirmed EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations were eligible. Patients were required to have measurable disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Patients were required to be EGFR tyrosine kinase inhibitor-naive. The primary objective was objective response rate, and secondary objectives were progression-free survival, safety, and overall survival. The study used a two-stage design with a plan to enroll 17 patients in the first stage, and the study was terminated after the first stage due to slow accrual. RESULTS: Between May 2018 and March 2020, 17 patients were enrolled and received study therapy. The median age of patients was 70 years (interquartile range 62-76), the majority were female (n = 11), had a performance status of 1 (n = 10), and five patients had brain metastases at baseline. The objective response rate was 47% [95% confidence interval (CI) 23% to 72%], and the radiographic responses observed were partial response (n = 8), stable disease (n = 8), and progressive disease (n = 1). The median progression-free survival was 10.5 months (95% CI 5.0-15.2 months), and the median OS was 13.8 months (95% CI 7.3-29.2 months). The median duration on treatment was 6.1 months (range 3.6-11.9 months), and the most common adverse events (regardless of attribution) were diarrhea, fatigue, anorexia, weight loss, and dyspnea. CONCLUSIONS: This trial suggests osimertinib has activity in patients with these uncommon EGFR mutations.

Development and inter-laboratory validation of the VISAGE enhanced tool for age estimation from semen using quantitative DNA methylation analysis.

The analysis of DNA methylation has become an established method for chronological age estimation. This has triggered interest in the forensic community to develop new methods for age estimation from biological crime scene material. Various assays are available for age estimation from somatic tissues, the majority from blood. Age prediction from semen requires different DNA methylation markers and the only assays currently developed for forensic analysis are based on SNaPshot or pyrosequencing. Here, we describe a new assay using massively parallel sequencing to analyse 13 candidate CpG sites targeted in two multiplex PCRs. The assay has been validated by five consortium laboratories of the VISible Attributes through GEnomics (VISAGE) project within a collaborative exercise and was tested for reproducible quantification of DNA methylation levels and sensitivity with DNA methylation controls. Furthermore, DNA extracts and stains on Whatman FTA cards from two semen samples were used to evaluate concordance and mimic casework samples. Overall, the assay yielded high read depths (> 1000 reads) at all 13 marker positions. The methylation values obtained indicated robust quantification with an average standard deviation of 2.8% at the expected methylation level of 50% across the 13 markers and a good performance with 50 ng DNA input into bisulfite conversion. The absolute difference of quantifications from one participating laboratory to the mean quantifications of concordance and semen stains of remaining laboratories was approximately 1%. These results demonstrated the assay to be robust and suitable for age estimation from semen in forensic investigations. In addition to the 13-marker assay, a more streamlined protocol combining only five age markers in one multiplex PCR was developed. Preliminary results showed no substantial differences in DNA methylation quantification between the two assays, indicating its applicability with the VISAGE age model for semen developed with data from the complete 13-marker tool.

A Comparison of Forensic Age Prediction Models Using Data From Four DNA Methylation Technologies.

Individual age estimation can be applied to criminal, legal, and anthropological investigations. DNA methylation has been established as the biomarker of choice for age prediction, since it was observed that specific CpG positions in the genome show systematic changes during an individual's lifetime, with progressive increases or decreases in methylation levels. Subsequently, several forensic age prediction models have been reported, providing average age prediction error ranges of ±3-4 years, using a broad spectrum of technologies and underlying statistical analyses. DNA methylation assessment is not categorical but quantitative. Therefore, the detection platform used plays a pivotal role, since quantitative and semi-quantitative technologies could potentially result in differences in detected DNA methylation levels. In the present study, we analyzed as a shared sample pool, 84 blood-based DNA controls ranging from 18 to 99 years old using four different technologies: EpiTYPER®, pyrosequencing, MiSeq, and SNaPshotTM. The DNA methylation levels detected for CpG sites from ELOVL2, FHL2, and MIR29B2 with each system were compared. A restricted three CpG-site age prediction model was rebuilt for each system, as well as for a combination of technologies, based on previous training datasets, and age predictions were calculated accordingly for all the samples detected with the previous technologies. While the DNA methylation patterns and subsequent age predictions from EpiTYPER®, pyrosequencing, and MiSeq systems are largely comparable for the CpG sites studied, SNaPshotTM gives bigger differences reflected in higher predictive errors. However, these differences can be reduced by applying a z-score data transformation.

Reliability of the Modified TICI Score among Endovascular Neurosurgeons.

BACKGROUND AND PURPOSE: The modified TICI score is the benchmark for quantifying reperfusion after mechanical thrombectomy. There has been limited investigation into the reliability of this score. We aim to identify intra-rater and inter-rater reliability of the mTICI score among endovascular neurosurgeons. MATERIALS AND METHODS: Four independent endovascular neurosurgeons (raters) reviewed angiograms of 67 patients at 2 time points. κ statistics assessed inter- and intrarater reliability and compared raters'-versus-proceduralists' scores. Reliability was also assessed for occlusion location and by dichotomizing modified TICI scores (0-2a versus 2b-3). RESULTS: Interrater reliability was moderate-to-substantial, weighted κ = 0.417-0.703, overall κ = 0.374 (P < .001). The dichotomized modified TICI score had moderate-to-substantial interrater agreement, κ statistics = 0.468-0.715, overall κ = 0.582 (P < .001). Intrarater reliability was moderate-to-almost perfect, weighted κ = 0.594-0.81. The dichotomized modified TICI score had substantial-to-almost perfect reliability, κ = 0.632-0.82. Proceduralists had fair-to-moderate agreement with raters, weighted κ = 0.348-0.574, and the dichotomized modified TICI score had fair-to-moderate agreement, κ = 0.365-0.544. When proceduralists and raters disagreed, proceduralists' scores were higher in 79.6% of cases. M1 followed by ICA occlusions had the highest agreement. CONCLUSIONS: The modified TICI score is a practical metric for assessing reperfusion after mechanical thrombectomy, though not without limitations. Agreement improved when scores were dichotomized around the clinically relevant threshold of successful revascularization. Interrater reliability improved with time, suggesting that formal training of interventionalists may improve reporting reliability. Agreement of the modified TICI scale is best with M1 and ICA occlusion and becomes less reliable with more distal or posterior circulation occlusions. These findings should be considered when developing research trials.

Does autoimmune hypothyroidism increase the risk of neurovascular complications in type 1 diabetes?

BACKGROUND: Type 1 diabetes (T1DM) often coexists with other autoimmune diseases, most commonly with hypothyroidism. To date, the influence of coexisting autoimmune hypothyroidism (AHT) on the course of chronic neurovascular complications of autoimmune diabetes has not been established. The aim of the study was to assess the relationship between AHT and the occurrence of chronic T1DM complications. METHODS: The study group comprised 332 European Caucasian participants with T1DM [165 (49.7%) men]. AHT was recognized in subclinical and overt hypothyroidism and confirmed by the presence of anti-thyroid autoantibodies: anti-peroxidase (ATPO) and/or anti-thyroglobulin (ATg) and ultrasonography (hypoechogenicity, parenchymal heterogeneity, lymph nodes assessment). RESULTS: In the analyzed group, 48.5% of patients were diagnosed with at least one neurovascular complication. At the time of enrollment, 16.3% of participants were diagnosed with AHT. Patients with AHT, compared to those without AHT, were characterized by a higher prevalence of neurovascular complications (64.8 vs. 45.3%; P = 0.009) and retinopathy (55.6 vs. 38.9%; P = 0.02). There were significant differences between groups with and without neurovascular complications, with regard to classic risk factors for chronic diabetes complications: age, T1DM duration, SBP, DBP, HbA1c, TG, eGFR and hypertension prevalence. In the multivariate logistic regression analysis, AHT was an independent predictor of neurovascular complications after adjusting for age, DBP, HbA1c and TG (odds ratio, 2.40; 95% confidence interval, 1.17-4.92; P = 0.02). CONCLUSIONS: AHT coexisting with T1DM was associated with a higher incidence of neurovascular complications.

Anti-tumor activity of the MDM2-TP53 inhibitor BI-907828 in dedifferentiated liposarcoma patient-derived xenograft models harboring MDM2 amplification.

PURPOSE: Dedifferentiated liposarcoma (DDLPS) is a soft tissue malignancy characterized by amplification of the mouse double minute 2 homolog (MDM2) gene. MDM2 is a negative regulator of tumor protein 53 (TP53). We tested the in vivo efficacy of BI-907828, a small molecule inhibitor of the MDM2-TP53 interaction, in two DDLPS patient-derived xenografts (PDX). METHODS: Partially immunodeficient mice were bilaterally engrafted with UZLX-STS3 (n = 24) and UZLX-STS5 (n = 24) human DDLPS tissue harboring MDM2 amplifications. Mice were grouped as follows: (a) vehicle (0.5% hydroxyethylcellullose) 10 ml/kg daily per os (p.o.); (b) doxorubicin 5 mg/kg weekly intraperitoneally (i.p.); (c) BI-907828 2.5 mg/kg daily p.o. and (d) BI-907828 10 mg/kg daily p.o. The treatment lasted for 15 days, all mice treated with BI-907828 were followed for 37 days post-treatment. Efficacy was assessed by tumor volume and histopathological evaluation. RESULTS: The 15-day treatment with 2.5 mg/kg and 10 mg/kg BI-907828 significantly inhibited tumor growth in UZLX-STS5 and -STS3 (p < 0.0001 compared to control for both models). All UZLX-STS5 and -STS3 tumors treated with BI-907828 decreased in size during treatment, and BI-907828-treated UZLX-STS5 tumors even disappeared completely. During the follow-up period, no tumor regrowth was observed in the UZLX-STS5 model and both doses of BI-907828 led to a pathological complete response, whereas a dose-dependent regrowth was seen in the UZLX-STS3 model. CONCLUSION: BI-907828 showed significant anti-tumor activity in DDLPS PDX harboring MDM2 amplifications, providing a strong rationale for early clinical testing of BI-907828 in a DDLPS patient population.

Paraoxonase 1: The Lectin-Like Oxidized LDL Receptor Type I and Oxidative Stress in the Blood of Men with Type II Obesity.

OBJECTIVES: Obesity has serious consequences such as the onset of metabolic syndrome, type 2 diabetes, atherosclerosis, or cardiovascular complications. The aim of this study was to evaluate the levels of paraoxonase 1 (PON1), lectin-like oxidized LDL receptor-1 (LOX-1), antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), and lipid peroxidation processes in the course of obesity. METHODS: 28 men took part in the experiment. Fourteen of them were obese; the control group consisted of 14 physically active men without obesity features. The concentrations of malondialdehyde (MDA), PON1, LOX-1, and tumor necrosis factor α (TNFα) as well as the activities of erythrocytic SOD, CAT, and GPx were determined in the study. RESULTS: Statistically significant higher MDA, LOX-1, and TNFα levels were observed in obese subjects. Conversely, lower concentrations of PON1 in obese men were found. CONCLUSIONS: An imbalance in oxidation-reduction processes accompanies obesity. Moreover, inflammatory cytokines and atherosclerotic complications are involved in the obesity process. The obtained results suggest that the studied parameters may be independent prognostic markers preceding the development of cardiovascular and metabolic complications in people afflicted with type II obesity.

Urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, uromodulin, and cystatin C concentrations in an experimental rat model of ascending acute kidney injury induced by pyelonephritis.

Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C (CysC), uromodulin (UMOD), and some interleukins (IL-6 and IL-18) can be considered as diagnostic markers of acute kidney injury (AKI). The aim of this study was to verify the applicability of four urinary (u) markers, namely uNGAL, uKIM-1, uCysC, and uUMOD, for the diagnosis of ascending AKI induced by bacterial pyelonephritis. The study included 30 female rats that were divided into three groups (n = 10 each) and were inoculated transurethrally with various doses of Escherichia coli to induce isolated pyelonephritis (group 1, 105 CFU/ml), pyelonephritis-induced AKI (group 2, 107 CFU/ml), or AKI and urosepsis (group 3, 109 CFU/ml). The inoculate contained a highly virulent E. coli strain isolated from a patient with pyelonephritis. Urine samples were obtained prior to the inoculation and 7, 14, and 21 days thereafter. The concentrations of all assessed proteins were determined in the urine samples by ELISA. All the study groups showed elevated concentrations of uNGAL and uCysC at all study time points. The concentrations of uKIM-1 in group 1 were the same as that at the baseline, whereas it was elevated in groups 2 and 3 at all study time points. The concentrations of uUMOD in groups 1 and 2 tended to decrease with the time from inoculation, whereas it rapidly increased in group 3 at 21 days postinfection. uKIM-1 seems to be the only marker of ascending AKI associated with urinary tract infection. Elevated concentrations of uNGAL, uCysC, and uUMOD were found in both AKI and isolated pyelonephritis. Thus, it can be concluded that none of these markers can be used as a single diagnostic marker of ascending AKI, as it may produce false-negative results, leading to incorrect diagnosis, lack of adequate treatment, and increased mortality risk.

Activity and safety of crizotinib in patients with alveolar soft part sarcoma with rearrangement of TFE3: European Organization for Research and Treatment of Cancer (EORTC) phase II trial 90101 'CREATE'.

Background: Alveolar soft part sarcoma (ASPS) is an orphan malignancy associated with a rearrangement of transcription factor E3 (TFE3), leading to abnormal MET gene expression. We prospectively assessed the efficacy and safety of the MET tyrosine kinase inhibitor crizotinib in patients with advanced or metastatic ASPS. Patients and methods: Eligible patients with reference pathology-confirmed ASPS received oral crizotinib 250 mg bd. By assessing the presence or absence of a TFE3 rearrangement, patients were attributed to MET+ and MET- sub-cohorts. The primary end point was the objective response rate (ORR) according to local investigator. Secondary end points included duration of response, disease control rate (DCR), progression-free survival (PFS), progression-free rate, overall survival (OS) and safety. Results: Among 53 consenting patients, all had a centrally confirmed ASPS and 48 were treated. A total of 45 were eligible, treated and assessable. Among 40 MET+ patients, 1 achieved a confirmed partial response (PR) that lasted 215 days and 35 had stable disease (SD) as best response (ORR: 2.5%, 95% CI 0.6% to 80.6%). Further efficacy end points in MET+ cases were DCR: 90.0% (95% CI 76.3% to 97.2%), 1-year PFS rate: 37.5% (95% CI 22.9% to 52.1%) and 1-year OS rate: 97.4% (95% CI 82.8% to 99.6%). Among 4 MET- patients, 1 achieved a PR that lasted 801 days and 3 had SD (ORR: 25.0%, 95% CI 0.6% to 80.6%) for a DCR of 100% (95% CI 39.8% to 100.0%). The 1-year PFS rate in MET- cases was 50% (95% CI 5.8% to 84.5%) and the 1-year OS rate was 75% (95% CI 12.8% to 96.1%). One patient with unknown MET status due to technical failure achieved SD but stopped treatment due to progression after 17 cycles. The most common crizotinib-related adverse events were nausea [34/48 (70.8%)], vomiting [22/48 (45.8%)], blurred vision [22/48 (45.8%)], diarrhoea (20/48 (41.7%)] and fatigue [19/48 (39.6%)]. Conclusion: According to European Organization for Research and Treatment of Cancer (EORTC) efficacy criteria for soft tissue sarcoma, our study demonstrated that crizotinib has activity in TFE3 rearranged ASPS MET+ patients. Clinical trial number: EORTC 90101, NCT01524926.

Activity and safety of crizotinib in patients with advanced clear-cell sarcoma with MET alterations: European Organization for Research and Treatment of Cancer phase II trial 90101 'CREATE'.

BACKGROUND: Clear-cell sarcoma (CCSA) is an orphan malignancy, characterized by a specific t(12;22) translocation, leading to rearrangement of the EWSR1 gene and overexpression of MET. We prospectively investigated the efficacy and safety of the tyrosine kinase inhibitor crizotinib in patients with advanced or metastatic CCSA. PATIENTS AND METHODS: Patients with CCSA received oral crizotinib 250 mg twice daily. Primary end point was objective response rate (ORR), secondary end points included duration of response, disease control rate (DCR), progression-free survival (PFS), progression-free rate (PFR), overall survival (OS), OS rate and safety. The study design focused on MET+ disease with documented rearrangement of the EWSR1 gene by fluorescence in situ hybridization. RESULTS: Among 43 consenting patients with the local diagnosis of CCSA, 36 had centrally confirmed CCSA, 28 of whom were eligible, treated and assessable. Twenty-six out of the 28 patients had MET+ disease, of whom one achieved a confirmed partial response and 17 had stable disease (SD) (ORR 3.8%, 95% confidence interval: 0.1-19.6). Further efficacy end points in MET+ CCSA were DCR: 69.2% (48.2% to 85.7%), median PFS: 131 days (49-235), median OS: 277 days (232-442). The 3-, 6-, 12- and 24-month PFR was 53.8% (34.6-73.0), 26.9% (9.8-43.9), 7.7% (1.3-21.7) and 7.7% (1.3-21.7), respectively. Among two assessable MET- patients, one had stable disease and one had progression. The most common treatment-related adverse events were nausea [18/34 (52.9%)], fatigue [17/34 (50.0%)], vomiting [12/34 (35.3%)], diarrhoea [11/34 (32.4%)], constipation [9/34 (26.5%)] and blurred vision [7/34 (20.6%)]. CONCLUSIONS: The PFS with crizotinib in MET+ CCSA is similar to results achieved first-line in non-selected metastatic soft tissue sarcomas with single-agent doxorubicin. The PFS is similar to results achieved with pazopanib in previously treated sarcoma patients. CLINICAL TRIAL NUMBER: EORTC 90101, EudraCT number 2011-001988-52, NCT01524926.

First detection of porcine circovirus type 3 on commercial pig farms in Poland.

Porcine circovirus type 3 (PCV3) is a novel circovirus species recently discovered in USA and China in cases of porcine dermatitis and nephropathy syndrome, reproductive failure, respiratory disease and multisystemic inflammation. This study reports on the first identification of PCV3 in Europe, in serum from pigs from Polish farms. A total of 1,050 serum samples were collected between 2014 and 2017 from sows and 3-20 weeks old pigs from 14 commercial farms representing different regions of Poland, different size and health status. The samples were pooled by 4-6 and tested with real-time PCR for PCV3. PCV3 DNA was detected in 12 of 14 farms (85.7%). On the PCV3-positive farms, the virus was detected in 5.9% to 65% serum pools. PCV3 was most common among weaned pigs and finishers (26.1% and 28.0% of serum pools, respectively). Sequence analysis of 359 nucleotide fragment of ORF2 showed highest identity of 99.7% to PCV3-US/SD2016 from USA. Our results indicate that PCV3 is a common virus among Polish pigs but no links to unexplained disease conditions were established.

Effect of Propionibacterium acnes (PA) injection on intervertebral disc degeneration in a rat model: Does it mimic modic changes?

INTRODUCTION: Multiple reports of bacterial isolates in human disc tissue have suggested a role of low-grade infection on intervertebral disc degeneration and modic changes (MC) generation. Animal models have been extensively used to study IDD; however, until recently, no consideration had been given to eventual infectious processes. To reproduce the phenomena by inoculating an infecting agent would support the infectious hypothesis. Therefore, we studied the effect of Propionibacterium acnes (PA) inoculation on rat-tails and determined whether it would produce MCs on the adjacent endplates. HYPOTHESIS: Disc infection with PA would accelerate IDD compared with the standard model and would also lead to MCs on the adjacent endplates. METHODS: Twelve Sprague-Dawley rats were randomized to receive a needle puncture in a caudal tail disc with either saline (control) or an inoculum of 5×107 CFU of strain 1a PA. Twelve weeks later, the rats were euthanized and the tails were analyzed. The main assessment criteria were obtained from the post-mortem MRI: T2 values of punctured discs and adjacent endplates, as well as disc volumes. A histological grading score for IDD was also used, measuring the morphology and cellularity of the nucleus and annulus, as well as endplate disruption. RESULTS: The median T2 value and disc volume were smaller in PA-punctured discs [T2 value: 30ms (23-44) vs. 61ms (38-132), respectively, P=0.01; 0.01mm3 (0.01-0.05) vs. 0.5mm3 (0.01-5.35), respectively; P=0.049]. There was no change in the adjacent endplates. There was no significant difference in histological grading between the test and control [13 (10-14) vs. 10.5 (6-13); P=0.05]. DISCUSSION: Inoculation of caudal discs with PA generated increased degeneration; however, no MCs were observed on the adjacent endplates. A better understanding of low-grade disc infections is still needed. LEVEL OF EVIDENCE: V (animal study).

Influence of Cytochrome P450, ABC and SLC Gene Polymorphisms on Imatinib Therapy Outcome of Patients with Gastrointestinal Stromal Tumours (GIST).

The efficacy of imatinib-based therapy depends on the proteins involved in its metabolism and transportation. Therefore, the aim of our study was to investigate the possible correlation of selected P450, ABC and SLC polymorphic variants and the outcome of imatinib therapy. A total of 101 patients with advanced, KIT/PDGFRA(+) GIST treated with imatinib were enrolled to the study. DNA was extracted from peripheral blood samples and genotypes were determined by PCR-RFLP and direct sequencing. Deviation from the Hardy-Weinberg equilibrium was only observed for rs2740574. None of the studied SNPs was associated with GIST time to progression. No significant correlation between any specific variant and time to progression was found in the group with KIT exon 11 mutation. However, individuals of at least three potentially unfavourable genotypes presented significantly shorter time to progression in comparison to patients with two or less unfavourable genotypes.

Nanostructure of Poly(Acrylic Acid) Adsorption Layer on the Surface of Activated Carbon Obtained from Residue After Supercritical Extraction of Hops.

The nanostructure of poly(acrylic acid) (PAA) adsorption layer on the surface of mesoporous-activated carbon HPA obtained by physical activation of residue after supercritical extraction of hops was characterized. This characterization has been done based on the analysis of determination of adsorbed polymer amount, surface charge density, and zeta potential of solid particles (without and in the PAA presence). The SEM, thermogravimetric, FTIR, and MS techniques have allowed one to examine the solid surface morphology and specify different kinds of HPA surface groups. The effects of solution pH, as well as polymer molecular weight and concentration, were studied. The obtained results indicated that the highest adsorption on the activated carbon surface was exhibited by PAA with lower molecular weight (i.e., 2000 Da) at pH 3. Under such conditions, polymeric adsorption layer is composed of nanosized PAA coils (slightly negatively charged) which are densely packed on the positive surface of HPA. Additionally, the adsorption of polymeric macromolecules into solid pores is possible.

Morphological assessment of thin basement membrane disease.

Thin basement membrane disease is more common than IgA nephropathy or Alport syndrome, which are also associated with the presence of erythrocyturia. Very few reports on the disorder are available in the Polish literature. The objective of this work was to analyze the results from 83 patients with thin basement membrane syndrome as well as to formulate a proposal of strict morphological assessment criteria for the disorder. Attention was drawn to the requirement of thickness of the lamina densa rather than the entire basement membrane thickness and a sufficiently high number of loops featuring thinned lamina densa, namely at least 80% of loops, being taken into account. Occurrence of other morphological changes associated with the disorder and clinical symptoms other than erythrocyturia was also highlighted.

The influence of aripiprazole and olanzapine on neurotransmitters level in frontal cortex of prenatally stressed rats.

OBJECTIVES: The study aims to verify whether alterations in the level of neurotransmitters have occurred in prenatally stressed rats (animal model of schizophrenia), and whether aripiprazole (ARI) and olanzapine (OLA) modify this level. METHODS: The effects of ARI (1.5mg/kg) and OLA (0.5mg/kg) were studied by means of microdialysis in freely moving rats (observation time 120min). The level of neurotransmitters (DA, 5-HT, NA) and their metabolites (DOPAC, HVA, 5-HIAA) was analyzed by HPLC with coulochemical detection. RESULTS: Obtained results indicate that after a single administration of ARI and OLA in the prenatally stressed rats the increase of DA, DOPAC, and 5-HT was observed. In turn ARI administration increase the level of HVA and 5-HIAA and also decrease the level of NA. After OLA administration the level of NA and HVA increased and no significant change in 5-HIAA was observed. CONCLUSION: Alterations observed as a result of ARI and OLA administration may be pivotal in identifying animal models of mental disorders and in the analysis of neuroleptics effectiveness.