Fluorescence in situ hybridization BCR/ABL fusion signal rate in interphase nuclei of healthy volunteer donors: a test study for establishing false positive rate

Fluorescence in situ hybridization (FISH) using chromosome-specific DNA probes is rapidly becoming a part of clinical laboratory practice. However, as a relatively new clinical test, it is not yet standardized and for practical reasons each laboratory must establish its own criteria. For this purpose we have evaluated the specificity of a dual-color BCR/ABL translocation probe by establishing the range of BCR/ABL fusion-positive scores in a healthy donor group. The false positive rate (FPR), determined by the percent of FISH BCR/ABL fusion-positive cells found in the specimens of healthy donors, was estimated at 2.3% (mean = 1%-4%). Thus the cut-off value for false positive nuclei was set at 5%.     

Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships

This review focuses on recent advances in the structure-function relationships of thyroid-stimulating hormone (TSH) and its receptor. TSH is a member of the glycoprotein hormone family constituting a subset of the cystine-knot growth factor superfamily. TSH is produced by the pituitary thyrotrophs and released to the circulation in a pulsatile manner. It stimulates thyroid functions using specific membrane TSH receptor (TSHR) that belongs to the superfamily of G protein-coupled receptors (GPCRs). New insights into the structure-function relationships of TSH permitted better understanding of the role of specific protein and carbohydrate domains in the synthesis, bioactivity, and clearance of this hormone. Recent progress in studies on TSHR as well as studies on the other GPCRs provided new clues regarding the molecular mechanisms of receptor activation. Such advances are a result of extensive site-directed mutagenesis, peptide and antibody approaches, detailed sequence analyses, and molecular modeling as well as studies on naturally occurring gain- and loss-of-function mutations. This review integrates expanding information on TSH and TSHR structure-function relationships and summarizes current concepts on ligand-dependent and -independent TSHR activation. Special emphasis has been placed on TSH domains involved in receptor recognition, constitutive activity of TSHR, new insights into the evolution of TSH bioactivity, and the development of high-affinity TSH analogs. Such structural, physiological, pathophysiological, evolutionary, and therapeutic implications of TSH-TSHR structure-function studies are frequently discussed in relation to concomitant progress made in studies on gonadotropins and their receptors.     

Silver-Staining Nucleolar Organizer Region Quantification in Pituitary Adenomas

Nucleolar organizer regions (NORs) are segments of DNA, encoding for ribosomal RNA. They are associated with argyrophilic proteins and, thus, they can be localized through silver staining. A correlation has been shown between the number, the size, or the intranuclear localization of AgNORs, and the proliferative activity of cells. The aim of this study was to examine numerous features of AgNORs in pituitary adenomas and to relate them to immunohistochemical typing of tumor. Histologic slides from 32 pituitary tumors and one normal pituitary were silver-stained and analyzed with a computerized system for microscopic image analysis, supported by an AgNORmeter95 program. All the tumors were also immunocyto chemically characterized. We have found that gonadotropinomas, when compared with plurihormonal adenomas, revealed a lower proportion of nuclei with a single AgNOR and a higher percentage of marginal dots. Recurrent adenomas, when compared with primary adenomas, showed a higher proportion of nuclei with three AgNOR dots, a larger total area of dots in the nuclei, and a higher standard deviation of the AgNOR dot area in the nucleus. Adenomas immunopositive for prolactin, when compared with immunonegative ones, showed a larger mean area of the AgNOR dot, a larger area of the biggest dot in the nucleus, and a higher proportion of nuclei within a single dot. These results suggest that the estimated parameters of AgNOR dots differ according to tumor aggressiveness and to the hormone immunopositivity of pituitary adenomas.     

Effect of agomelatine in the chronic mild stress model of depression in the rat.

Chronic mild stress (CMS), a well-validated model of depression, was used to study the effects of the melatonin agonist and selective 5-HT(2C) antagonist agomelatine (S 20098) in comparison with melatonin, imipramine, and fluoxetine. All drugs were administered either 2 h before (evening treatment) or 2 h after (morning treatment) the dark phase of the 12-h light/dark cycle. Chronic (5 weeks) evening treatment with agomelatine or melatonin (both at 10 and 50 mg/kg i.p.) dose-dependently reversed the CMS-induced reduction in sucrose consumption. The magnitude and time course of the action of both drugs was comparable to that of imipramine and fluoxetine (both at 10 mg/kg i.p.); however, melatonin was less active than agomelatine at this dose. The effect of evening administration of agomelatine and melatonin was completely inhibited by an acute injection of the MT(1)/MT(2) antagonist, S 22153 (20 mg/kg i.p.), while the antagonist had no effect in animals receiving fluoxetine or imipramine. When the drugs were administered in the morning, agomelatine caused effects similar to those observed after evening treatment (with onset of action faster than imipramine) but melatonin was ineffective. Moreover, melatonin antagonist, S 22153, did not modify the intakes in stressed animals receiving morning administration of agomelatine and in any other control and stressed groups tested in this study. These data demonstrate antidepressant-like activity of agomelatine in the rat CMS model of depression, which was independent of the time of drug administration. The efficacy of agomelatine is comparable to that of imipramine and fluoxetine, but greater than that of melatonin, which had no antidepressant-like activity after morning administration. While the evening efficacy of agomelatine can be related to its melatonin receptors agonistic properties, its morning activity, which was not inhibited by a melatonin antagonist, indicates that these receptors are certainly required, but not sufficient to sustain the agomelatine efficacy. It is therefore suggested that the antidepressant-like activity of agomelatine depends on some combination of its melatonin agonist and 5-HT(2C) antagonist properties.     

The technique of stump closure has no impact on post-pneumonectomy bronchopleural fistula in the non-small cell lung cancer—a cross-sectional study

BackgroundPneumonectomy is a high-risk radical resection procedure, with bronchopleural fistula (BPF) being its most challenging and severe complication. This study aimed to assess the surgical risk factors and the impact of the bronchial stump closure technique on the incidence of the BPF.MethodsThis is a single-center, cross-sectional study of the medical records of 455 post-pneumonectomy patients operated due to non-small cell lung cancer (NSCLC) in 2006–2017. We analyzed the following variables and their influence on the occurrence of the BPF: operation side, surgical techniques (i.e., manual suture or the stapler), stump buttressing, the extension of pneumonectomy, comorbidities, and postoperative complications.ResultsBPF occurred in 7.47% of post-pneumonectomy patients. BPF was more prevalent in right-sided pneumonectomy versus left-sided (10.98% vs. 5.32%; P=0.026). The use of a stapler or manual suture was not associated with the incidence of the BPF (7.96% vs.7.09%, P=0.72). There were no significant differences in the occurrence of BPF among bronchial stump buttressing with the parietal pleura (P=0.80), intercostal muscle flap (IMF) (P=0.46), and pericardial fat pad (P=0.88). When comparing data from 2006–2012 with those from 2013–2017, we found a steady decrease in the number of performed stump reinforcements, but this was not associated with a higher risk of BPF.ConclusionsThe method used for stump closure, additional tissue buttressing of the bronchial stump and year of the surgery had no significant impact on the occurrence of BPF. Only right-sided pneumonectomy was associated with higher BPF occurrence.     

Oestrogen receptor α gene polymorphisms,insomnia, and cognitive functions in perimenopausal and postmenopausal women in non-manual employment

IntroductionA potential way to explain the relationships between sleep disorders and cognitive disorders during menopausal transition is the identification of genetic markers related to changes in cognitive functions, as well as changes in quality of sleep during menopause. The objective was an analysis of the relationship between sleep disorders and cognitive disorders, according to the possessed oestrogen receptor α gene polymorphism (ESR1) in perimenopausal and postmenopausal women.Material and methodsThe study included 300 women aged 44–66 years, employed as non-manual workers. A computerised battery of the Central Nervous System Vital Signs (CNS VS) test was used to diagnose cognitive functions. ESR1 polymorphisms were genotyped using PCR-RFLP methods. The Athens Insomnia Scale was used to diagnose sleep disorders.ResultsMore severe insomnia was related to worse complex memory, visual memory, and simple attention in the total group of examined women. More severe insomnia was related to worse simple attention in women with genotypes AG Xba I or TC Pvu II ESR1, in perimenopausal women with genotypes AG Xba I or TC Pvu II ESR1. During the postmenopausal period, the severity of insomnia negatively correlated with visual memory in carriers of Pvu II TT, and with reaction time in carriers of Xba I AA.ConclusionsThe results indicate an important role of oestrogen receptor α gene polymorphism in the modulation of the effect of insomnia on cognitive functions in peri- and postmenopausal women.     

The Role of Resveratrol in Eye Diseases—A Review of the Literature

Resveratrol (3,5,4′-trans-trihydroxystilbene) is a polyphenolic phytoalexin belonging to the stilbene family. It is commonly found in grape skins and seeds, as well as other plant-based foods. Oxidative stress and inflammation play a key role in the initiation and progression of age-related eye disorders (glaucoma, cataracts, diabetic retinopathy, and macular degeneration) that lead to a progressive loss of vision and blindness. Even though the way resveratrol affects the human body and the course of many diseases is still the subject of ongoing scientific research, it has been shown that the broad spectrum of anti-inflammatory and neuroprotective properties of resveratrol has a beneficial effect on eye tissues. In our research, we decided to analyze the current scientific literature on resveratrol, its possible mechanisms of action, and its therapeutic application in order to assess its effectiveness in eye diseases.     

Comparison of different lymph node staging systems for predicting prognosis in patients with colon cancer who have undergone surgical resection

At present, the most widely used lymph node (LN) staging system in colon cancer is number of metastatic LNs in pathological assessment (pN) from the 8th edition of the TNM American Joint Committee on Cancer/Union for International Cancer Control staging system, which considers the number of metastatic LNs, omitting the total number of dissected LNs. The aim of the present study was to compare the prognostic performance of pN with alternative LN staging systems, including LN ratio (LNR) and log odds of positive LNs (LODDS). The clinical and histopathological data of 298 patients with colon cancer who underwent elective surgical resection in a single surgical centre were analysed. LNR and LODDS cut-off values according to two previous studies were selected to separate patients into different subgroups. Univariate and multivariate analyses were performed to distinguish prognostic factors. The three-step multivariate analysis showed that LNR was a superior prognostic indicator compared with pN and LODDS. Additionally, the Akaike Information Criterion, a measure of the relative quality of statistical models, confirmed that LNR displayed the best prognostic performance. Similarly, in a subpopulation of patients with number of dissected LNs (NDLN) ≥12, LNR was the most accurate LN staging system in relation to prognosis. In a subpopulation with NDLN <12, there was no significant difference in LN classification prognosis of 5-year overall survival; however, LNR and LODDS were more independent of NDLN than pN. Among the three LN classifications, LNR is the most accurate LN staging system for predicting prognosis for patients with colon cancer who have undergone surgical resection, particularly those with metastatic LNs subjected to adequate lymphadenectomy.     

Research on the Release of Dangerous Compounds from the BTEX and PAHs Groups in Industrial Casting Conditions

The assessment of the harmfulness of moulding and core sands is mainly based on investigations of compositions of gases emitted by liquid casting alloys during the mould pouring. The results of investigations of moulding sands obtained under industrial conditions are presented in this paper. A unique research stand was designed and built for this aim. It allowed us to determine emissions of gases at individual stages of casting a mass up to 50 kg. This approach enables simulation of foundry conditions. Moulding sands bound by organic binders (phenol-formaldehyde; furan), inorganic binders and green sand, were subjected to investigations. The composition of gases that evolved during the individual stages, pouring, cooling and knocking out, was tested each time, and the contents of Polycyclic Aromatic Hydrocarbons (PAHs) and benzene, toluene, ethylbenzene, and xylenes (BETX) were analysed. Investigations indicated that the emission of gases from sands with inorganic binders is negligible when compared with the emission of gases from sands with organic binders. The emission of gases from green sand is placed in the middle of the scale. As an example: the sand with furan resin emitted 84 mg of BTEX (in recalculation for 1 kg of sand) while from sands with inorganic binders there was a maximum of 2.2 mg (for 1 kg of sand). In the case of sands with inorganic binders, MI and MC sands indicated comparable and very low emissions of gases from the PAHs group, at the level of 0.018 mg and 0.019 mg for 1 kg of sand, respectively. The higher emission of PAHs from MG sand is the result of its different way of hardening (a binder was of an organic character) than of sands MI and MC.