Sunitinib-induced hypothyroidism predicts progression-free survival in metastatic renal cell carcinoma patients

Sunitinib is a tyrosine kinase inhibitor (TKI) used in treatment of metastatic renal cell carcinoma (mRCC), gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. One of the most common side effects related to sunitinib is hypothyroidism. Recent trials suggest correlation between the incidence of hypothyroidism and treatment outcome in patients treated with TKI. This study evaluates whether development of hypothyroidism is a predictive marker of progression-free survival (PFS) in patients with mRCC treated with sunitinib. Twenty-seven patients diagnosed with clear cell mRCC, after nephrectomy and in ‘good’ or ‘intermediate’ MSKCC risk prognostic group, were included in the study. All patients received sunitinib as a first-line treatment on a standard schedule (initial dose 50 mg/day, 4 weeks on, 2 weeks off). The thyroid-stimulating hormone serum levels were obtained at the baseline and every 12 weeks of treatment. In statistic analyses, we used Kaplan–Meier method for assessment of progression-free survival; for comparison of survival, we used log-rank test. In our study, the incidence of hypothyroidism was 44%. The patients who had developed hypothyroidism had better median PFS to patients with normal thyroid function 28,3 months [95% (CI) 20.4–36.2 months] versus 9.8 months (6.4–13.1 months). In survival analysis, we perceive that thyroid dysfunction is a predictive factor of a progression-free survival (PFS). In the unified group of patients, the development of hypothyroidism during treatment with sunitinib is a positive marker for PFS. During that treatment, thyroid function should be evaluated regularly

Clustering of Staphylococcus aureus bovine mastitis strains from regions of Central-Eastern Poland based on their biochemical and genetic characteristics

Staphylococcus aureus strains were isolated from mastitic milk of cows with infected mammary glands. The animals were living in 12 different farms near Lublin, in Central-Eastern Poland. A biochemical identification method based on enzymatic assay was performed, followed by haemolytic and proteolytic tests. PCR-RFLP targeted on the gap gene allowed the genetic identification of strains at the species level and verified phenotypic identification results. A molecular typing method using triplex PCR was performed to recognize the genetic similarity of the analyzed strains. DNA microarray hybridization (StaphyType, Alere Technologies) was used for detection of antibiotic resistance and virulence associated markers. The results obtained indicate high genetic similarity in strains isolated from the same sites. High genetic similarities were also detected between strains isolated from cows from different farms of the same region. A slightly lower similarity was noted however, in strains from various regions indicating that the strains are herd specific and that the cow's infections caused by S. aureus were of a clonal character. In 21 representative isolates selected for DNA-microarray testing, only fosfomycin (fosB) and penicillin resistance markers (blaZ, blaI, blaR) were detected. The presence of genes coding for haemolysins (lukF, lukS, hlgA, hla, hld, hlb), proteases (aur, sspA, sspB, sspP), enterotoxins (entA, entD, entG, entI, entJ, entM, entN, entO, entR, entU, egc-cluster), adhesins (icaA, icaC, icaD, bbp, clfA, clfB, fib, fnbA, map, vwb) or immune evasion proteins (scn, chp, sak) was common and, with exceptions, matched triplex PCR-defined clusters

Effect of citrullinated bradykinin on regenerative and inflammatory responses in a model of human gingival fibroblasts.

Porphyromonas gingivalis stanowi główny czynnik etiologiczny choroby zapalnej przyzębia (paradontozy). Jednym z czynników wirulencji tej bakterii jest deiminaza peptydyloargininowa (PPAD), która katalizuje reakcję cytrulinacji w cząsteczkach peptydów i białek, polegającą na przekształceniu reszt argininowych do cytruliny. Enzym produkowany przez P. gingivalis preferuje argininę zlokalizowaną na C–końcu cząsteczek peptydów i białek. W czasie rozwoju stanu zapalnego w tkance dziąsłowej stwierdza się zwiększony napływ mediatorów zapalnia, cytokin i chemokin. Jednym z istotnych mediatorów reakcji zapalnej jest bradykinina, posiadająca na C końcu cząsteczki argininę, co czyni ją potencjalnym substratem do cytrulinacji. Celem niniejszej pracy było zbadanie wpływu cytrulinowanej bradykininy na właściwości regeneracyjne oraz odpowiedź zapalną ludzkich fibroblastów dziąsłowych. Wpływ zmodyfikowanej bradykininy na właściwości regeneracyjne fibroblastów sprawdzano poprzez badanie proliferacji i migracji komórek. Natomiast odpowiedź zapalną badano poprzez pomiar stężenia prostaglandyny E2 i interleukiny–6 oraz analizę ekspresji genów biorących udział w szlaku powstawania prostaglandyny E2 tj. cyklooksygenazy–2 oraz mikrosomalnej syntazy 1 prostaglandyny E.Na podstawie przeprowadzonych badań wykazano, że stymulacja cytrulinowaną bradykininą, jak również kostymulacja cytrulinowaną bradykininą i nabłonkowym czynnikiem wzrostu hamowała właściwości regeneracyjne fibroblastów dziąsłowych. Nie stwierdzono efektu modyfikowanego peptydu na odpowiedź zapalną komórek dziąsłowych, jednak kostymulacje komórek zmodyfikowaną bradykininą z nabłonkowym czynnikiem wzrostu albo czynnikiem martwicy guza skutkowaly wzrostem stężenia badanych cytokin prozapalnych (PGE2 i IL-6) i ekspresji enzymów COX–2 i mPGES–1. Uzyskane wyniki pozwalają wysnuć hipotezę, że cytrulinowana bradykinina poprzez współdziałanie z czynnikami wzrostowymi lub cytokinami prozapalnymi może potęgować odpowiedź zapalną komórek podścieliska dziąsłowego oraz hamować regenerację uszkodzonej tkanki w przebiegu choroby zapalnej przyzębia.Porphyromonas gingivalis is a principal aetiologic factor responsible for periodontitis. One of the virulence factors of the bacteria is peptidylarginine deiminase (PPAD), an enzyme which catalyzes conversion of arginine to citrulline, with a preference for arginine localized at the C–terminal side of peptide molecules. In the course of inflammation gingival tissue is infiltrated by a great number of inflammatory mediators, cytokines and chemokines. One such example is bradykinin–a peptide which possesses C–terminal arginine in the molecule, what make it an attractive candidate for citrullination. The aim of this study was to analyze the effect of citrullinated bradykinin on regenerative and inflammatory responses in a model of human gingival fibroblasts. The effect of modified bradykinin on regenerative response was evaluated through cell proliferation and migration analyses. The inflammatory response was studied by evaluation of prostaglandin E2 and interleukin–6 levels as well as through the analyses of cyclooxygenase–2 and microsomal synthase prostaglandin 1 genes expression. Results obtained in the present study indicated that citrullinated bradykinin as well as cotreatment by means of citrullinated bradykinin and epidermal growth factor inhibited regenerative response of gingival fibroblasts. Modified bradykinin did not affect inflammatory response, however cotreatment of cells with citrullinated bradykinin and epidermal growth factor or tumor necrosis factor α increased synthesis of both proinflammatory cytokines (PGE2 and IL-6) and expression of COX–2 and mPGES–1.In conclusion, citrullinated bradykinin while working in cooperation with growth factors or proinflammatory cytokines may induce the inflammatory response of gingival fibroblasts and inhibit regeneration of damaged tissue in the course of periodontitis

Corporate Social Responsibility Practices in the Energy Industry — Trends of Change

The purpose of the article is to analyse and evaluate corporate social responsibility practices as a response of companies to the expectations of a wide range of stakeholders. In the article, the authors perceive CSR practices as a way of conducting market activities in accordance with the expectations of stakeholders, with those not being a one-time act but a continuous effort to improve the areas of the company’s environment requiring support and the entity selected for analysis-which is a Polish energy industry capital group-Energa Group. It is a large entity whose activities can significantly and, in many ways, affect the environment. The analysis was based on secondary sources, including, in particular, the cyclical CSR reports and non-financial reports of the Energa Group. The research results show the trends of changes in CSR practices in the analysed company over the last 10 years (2011–2021), which can be used in the formulation of subsequent CSR programmes of the Energa Group and provide inspiration for other entities

Peptidylarginine deiminase from Porphyromonas gingivalis contributes to infection of gingival fibroblasts and induction of prostaglandin E_{2}-signaling pathway

Porphyromonas gingivalis (Pg) expresses the enzyme peptidylarginine deiminase (PPAD), which has a strong preference for C-terminal arginines. Due to the combined activity of PPAD and Arg-specific gingipains, Pg on the cell surface is highly citrullinated. To investigate the contribution of PPAD to the interaction of Pg with primary human gingival fibroblasts (PHGF) and Pg-induced synthesis of prostaglandin E2 (PGE2), PHGF were infected with wild-type Pg ATCC 33277, an isogenic PPAD-knockout strain (Δppad) or a mutated strain (C351A) expressing an inactive enzyme in which the catalytic cysteine has been mutated to alanine (PPAD(C351A)). Cells were infected in medium containing the mutants alone or in medium supplemented with purified, active PPAD. PHGF infection was assessed by colony-forming assay, microscopic analysis and flow cytometry. Expression of COX-2 and mPGES-1, key factors in the prostaglandin synthesis pathway, was examined by qRT-PCR, while PGE2 synthesis was evaluated by EIA. PHGF were infected more efficiently by wt-Pg than the Δppad strain, which correlated with strong induction of COX-2 and mPGES-1 expression by wt-Pg, but not by the PPAD activity-null mutant strains (ΔPPAD and C351A). The impaired ability of the ΔPPAD strain to adhere to and/or invade PHGF and both ΔPPAD and C351A to stimulate the PGE2-synthesis pathway was fully restored by the addition of purified PPAD. The latter effect was strongly inhibited by aspirin. Collectively, our results implicate PPAD activity, but not PPAD itself, as an important factor for gingival fibroblast infection and activation of PGE2 synthesis, the latter of which may strongly contribute to bone resorption and eventual tooth loss

The Differences in the Level of Anti-SARS-CoV-2 Antibodies after mRNA Vaccine between Convalescent and Non-Previously Infected People Disappear after the Second Dose—Study in Healthcare Workers Group in Poland

(1) Background: In many infections, antibodies play a crucial role in controlling infection. In COVID-19, the dynamics of the immune system response to SARS-CoV-2 is not fully understood. (2) Methods: The study was conducted on 120 healthcare workers from Dr. Antoni Jurasz University Hospital No. 1 in Bydgoszcz, between June and December 2020. In all participants, IgA and IgG antibody serum concentrations were measured using the semi-quantitative Anti-SARS-CoV-2 ELISA test (Euroimmun). After vaccination, in January and February 2021, antibody levels were examined using the quantitative IgG Anti-SARS-CoV-2 Quantivac ELISA test (Euroimmun). (3) Results: During the whole study period, the SARS-CoV-2 infection was confirmed in 29 (24.2%) participants. In all infected participants, IgA and IgG antibodies were detectable after infection by semi-quantitative serological tests. Levels of antibodies were higher one month after the first dose in the convalescents than in the non-previously infected participants. In this second group, the level of antibodies increased significantly after the second dose of vaccines compared to the first dose. (4) Conclusions: The level of antibodies after the first dose of vaccine in the convalescents’ group is higher than in the SARS-CoV-2 non-infected group, but the differences disappear after the second vaccination

Clonal Structure and Characterization of <i>Staphylococcus aureus</i> Strains from Invasive Infections in Paediatric Patients from South Poland: Association between Age, <i>spa</i> Types, Clonal Complexes, and Genetic Markers

<div><p>The aim of current study was to examine clonal structure and genetic profile of invasive <i>Staphylococcus aureus</i> isolates recovered from infants and children treated at the Jagiellonian University Children’s Hospital of Krakow, Poland. The 107 invasive <i>S</i>. <i>aureus</i> isolates, collected between February 2012 and August 2014, were analysed retrospectively. Antimicrobial susceptibility testing, <i>spa</i> typing and DNA microarray analysis were performed to determine clonal distribution, diversity and gene content in regard to patients characteristics. In total, 107 isolates were recovered from 88 patients with clinical symptoms of invasive bacterial infection. The final set of 92 non-duplicate samples included 38 MRSA isolates. Additionally, a set of 54 <i>S</i>. <i>aureus</i> isolates collected during epidemiological screening was genotyped and analysed. There were 72 healthcare-associated (HCA) and 20 community-onset (CO) infection events caused by 33 and 5 MRSA isolates, respectively. The majority of isolates were affiliated with the major European clonal complexes CC5 (t003, <i>spa</i>-CC 002), CC45 (<i>spa</i>-CC 015), CC7 or CC15 (t084, t091, <i>spa</i>-CC 084). Two epidemic clones (CC5-MRSA-II or CC45-MRSA-IV) dominated among MRSA isolates, while MSSA population contained 15 different CCs. The epidemiological screening isolates belonged to similar genetic lineages as those collected from invasive infection cases. The HCA infection events, <i>spa</i> types t003, t2642 or CC5 were significantly associated with infections occurring in neonates and children under 5 years of age. Moreover, carriage of several genetic markers, including <i>erm(A)</i>, <i>sea (N315)</i>, <i>egc-</i>cluster, <i>chp</i> was significantly higher in isolates obtained from children in this age group. The <i>spa</i> types t091 and t008 were underrepresented among patients aged 5 years or younger, whereas <i>spa</i> type t008, CC8 and presence of <i>splE</i> was associated with infection in children aged 10 years or older. The HCA-MRSA strains were most frequently found in children under 5 years, although the majority of invasive infections was associated with MSSA strains. Moreover, an association between age group of children from the study population and a specific strain genotype (<i>spa</i> type, clonal complex or genetic content) was observed among the patients.</p></div