Pulmonary blastoma in a pregnant woman: a case report and brief review of the literature.

BACKGROUND: Pulmonary blastoma (PB) comprises a rare heterogeneous group of lung tumours typically containing immature epithelial and mesenchymal structures that imitate the embryonic lung tissue and extremely rarely occurs during pregnancy. Although cough and haemoptysis are the most common PB symptoms, they usually indicate other serious pregnancy-related complications. CASE PRESENTATION: The article presents the unusual case of a 22-year-old pregnant woman diagnosed with PB during pregnancy. CONCLUSIONS: PB is characterized by poor prognosis and patients' outcome relies on a rapid diagnosis. Surgery remains the most common and effective treatment. Due to the extreme rarity, the literature contains only single mentions of PB in pregnancy, thus its impact on the course of pregnancy and the developing fetus remains unknown.

Adenylate kinases of thermophiles Aquifex aeolicus and Geobacillus stearothermophilus: biochemical and kinetic studies.

Adenylate kinases (AK) play a pivotal role in the regulation of cellular energy. The aim of our work was to achieve the overproduction and purification of AKs from two groups of bacteria and to determine, for the first time, the comprehensive biochemical and kinetic properties of adenylate kinase from Gram-negative Aquifex aeolicus (AKaq) and Gram-positive Geobacillus stearothermophilus (AKst). Therefore we determined KM and Vmax values, and the effects of temperature, pH, metal ions, donors of the phosphate groups and inhibitor Ap5A for both thermophilic AKs. The kinetic studies indicate that both AKs exhibit significantly higher affinity for substrates with the pyrophosphate group than for adenosine monophosphate. AK activation by Mg2+ and Mn2+ revealed that both ions are efficient in the synthesis of adenosine diphosphate and adenosine triphosphate; however, Mn2+ ions at 0.2-2.0 mmol/L concentration were more efficient in the activation of the ATP synthesis than Mg2+ ions. Our research demonstrates that zinc ions inhibit the activity of enzymes in both directions, while Ap5A at a concentration of 10 µmol/L and 50 µmol/L inhibited both enzymes with a different efficiency. Sigmoid-like kinetics were detected at high ATP concentrations not balanced by Mg2+, suggesting the allosteric effect of ATP for both bacterial AKs.

Biochemical Characterization of Recombinant UDPG-Dependent IAA Glucosyltransferase from Maize (Zea mays).

Here, we report a biochemical characterization of recombinant maize indole-3-acetyl-ß-d-glucose (IAGlc) synthase which glucosylates indole-3-acetic acid (IAA) and thus abolishes its auxinic activity affecting plant hormonal homeostasis. Substrate specificity analysis revealed that IAA is a preferred substrate of IAGlc synthase; however, the enzyme can also glucosylate indole-3-butyric acid and indole-3-propionic acid with the relative activity of 66% and 49.7%, respectively. KM values determined for IAA and UDP glucose are 0.8 and 0.7 mM, respectively. 2,4-Dichlorophenoxyacetic acid is a competitive inhibitor of the synthase and causes a 1.5-fold decrease in the enzyme affinity towards IAA, with the Ki value determined as 117 µM, while IAA-Asp acts as an activator of the synthase. Two sugar-phosphate compounds, ATP and glucose-1-phosphate, have a unique effect on the enzyme by acting as activators at low concentrations and showing inhibitory effect at higher concentrations (above 0.6 and 4 mM for ATP and glucose-1-phosphate, respectively). Results of molecular docking revealed that both compounds can bind to the PSPG (plant secondary product glycosyltransferase) motif of IAGlc synthase; however, there are also different potential binding sites present in the enzyme. We postulate that IAGlc synthase may contain more than one binding site for ATP and glucose-1-phosphate as reflected in its activity modulation.

Assessing the Interactions of Statins with Human Adenylate Kinase Isoenzyme 1: Fluorescence and Enzyme Kinetic Studies.

Statins are the most effective cholesterol-lowering drugs. They also exert many pleiotropic effects, including anti-cancer and cardio- and neuro-protective. Numerous nano-sized drug delivery systems were developed to enhance the therapeutic potential of statins. Studies on possible interactions between statins and human proteins could provide a deeper insight into the pleiotropic and adverse effects of these drugs. Adenylate kinase (AK) was found to regulate HDL endocytosis, cellular metabolism, cardiovascular function and neurodegeneration. In this work, we investigated interactions between human adenylate kinase isoenzyme 1 (hAK1) and atorvastatin (AVS), fluvastatin (FVS), pravastatin (PVS), rosuvastatin (RVS) and simvastatin (SVS) with fluorescence spectroscopy. The tested statins quenched the intrinsic fluorescence of hAK1 by creating stable hAK1-statin complexes with the binding constants of the order of 104 M-1. The enzyme kinetic studies revealed that statins inhibited hAK1 with significantly different efficiencies, in a noncompetitive manner. Simvastatin inhibited hAK1 with the highest yield comparable to that reported for diadenosine pentaphosphate, the only known hAK1 inhibitor. The determined AK sensitivity to statins differed markedly between short and long type AKs, suggesting an essential role of the LID domain in the AK inhibition. Our studies might open new horizons for the development of new modulators of short type AKs.

Can we minimize carbon footprint by using "greener" inhalers and improve clinical outcome at the same time in asthma therapy?

The treatment of patients with obstructive airway diseases is based on the use of inhalation preparations. Some of them, mainly including pressurized metered dose inhalers (pMDIs), contain compressed gases - hydrofluoroalkanes, which generate carbon dioxide emissions, creating the so-called carbon footprint. AIM: The aim of the study was to evaluate the consumption of individual active substances, the types of inhalers used and calculation of the carbon footprint of therapies in patients with asthma in 2018 and 2019 in Poland. MATERIALS AND METHODS: The ratio of pMDI vs DPI (dry powder inhaler) data and the data on using in patients with asthma long-acting ß2-agonists (LABAs), short-acting ß2-agonists antagonists (SABAs), long-acting muscarinic antagonists (LAMAs), LAMA+LABAs, LAMA+LABA+ICSs (inhaled corticosteroids) on Polish market during 2018 and 2019 were analyzed. The carbon footprint of such therapies was counted. Then, we studied the reduction of the carbon footprint for scenario A (reducing pMDI by 50%) and scenario B (reducing pMDI by 80%) in the following steps of analysis. RESULTS: The general structure of pMDI/DPI in Poland in asthma patients was not changed in 2019 vs 2018. The carbon footprint is primarily created by pMDI SABAs. In 2019 in Poland pMDI SABAs were 1.9 mio units (the same as in 2018), which generated 36.8 kt CO2e annually. Scenario A gives us a benefit of 17.4 kt CO2e reduction and scenario B brings us a benefit of 28.0 kt CO2e reduction of emissions. CONCLUSIONS: Despite Poland's ratification the Kigali amendment did not affect pMDI consumption by asthma patients and did not reduce the carbon footprint. The lower carbon footprint of DPIs should be considered alongside other factors when choosing inhalation devices.

What is new about ovarian malignancies?

Ovarian cancer is one of the most prevalent pathologies in gynaecology. This malignancy can be divided into 2 large groups: epithelial and non-epithelial. Because epithelial ovarian cancers (EOC) are the most commonly diagnosed, this paper focuses on the latest therapies associated with this disease. Due to the difficult diagnosis, EOC is frequently detected in the advanced stage. The treatment is usually complex and requires specialist knowledge. Advances and new ideas, such as identification of various genes and molecules that can serve as prognostic factors, might increase patients' chances of survival; they may contribute to optimization of patients' treatment, deciding whether to use aggressive treatment strategies, and predicting chemoresistance. Moreover, new strategies might also improve the quality of life of patients. The study aimed to analyse and discuss the latest reports on new methods of managing EOC.

The complexity of tumour angiogenesis based on recently described molecules.

Tumour angiogenesis is a crucial factor associated with tumour growth, progression, and metastasis. The whole process is the result of an interaction between a wide range of different molecules, influencing each other. Herein we summarize novel discoveries related to the less known angiogenic molecules such as galectins, pentraxin-3, Ral-interacting protein of 76 kDa (RLIP76), long non-coding RNAs (lncRNAs), B7-H3, and delta-like ligand-4 (DLL-4) and their role in the process of tumour angiogenesis. These molecules influence the most important molecular pathways involved in the formation of blood vessels in cancer, including the vascular endothelial growth factor (VEGF)-vascular endothelial growth factor receptor interaction (VEGFR), HIF1-a activation, or PI3K/Akt/mTOR and JAK-STAT signalling pathways. Increased expression of galectins, RLIP76, and B7H3 has been proven in several malignancies. Pentraxin-3, which appears to inhibit tumour angiogenesis, shows reduced expression in tumour tissues. Anti-angiogenic treatment based mainly on VEGF inhibition has proved to be of limited effectiveness, leading to the development of drug resistance. The newly discovered molecules are of great interest as a potential source of new anti-cancer therapies. Their role as targets for new drugs and as prognostic markers in neoplasms is discussed in this review.

Characterization of a Mixed-Valence Ru(II)/Ru(III) Ion-Pair Complex. Unexpected High-Frequency Electron Paramagnetic Resonance Evidence for Ru(III)-Ru(III) Dimer Coupling.

In this contribution, we report the synthesis and full characterization of the first mixed-valence Ru(II)/Ru(III) ion-pair complex, [RuII(bipy)2(pic)]+[cis-RuIIICl2(pic)2]-, in the solid state and in aqueous solution, where bipy = 2,2'-bipyridine and pic- = picolinate. In addition, unexpected high-frequency electron paramagnetic resonance evidence for interactions between two neighboring Ru(III) ions, resulting in a triplet state, S = 1, was found.

Incorporating immunohistochemical markers into screening methods for BRCA1-mutated breast cancer.

BRCA1-mutated breast cancer (BC) is responsible for approximately 25% of hereditary breast cancer cases. BRCA1 is a tumor suppressor protein regulating the cell cycle and DNA repair; therefore its dysfunctions play a significant role in carcinogenesis. BRCA1-mutated BC is associated with basal-like phenotype, lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in addition to frequent TP53 mutations and poor prognosis. Currently used criteria for genetic evaluation of BC for the risk of hereditary mutations are based on patients' age and family history, and therefore are prone to be imprecise or incomplete. This review discusses recently developed sets of immunohistochemical markers, promising independent markers (nestin, ALDH1, FOXO3, claudins, topoisomerase 1, EGFR) and their potential to be incorporated into clinical practice as a support tool in oncological counseling. This approach could be applied as a screening method for cost-effective selection of cases requiring genetic testing or adapted in pathology laboratories with limited access to molecular techniques. Although not all of the described predictor models have been validated yet, they could further improve the performance of BRCA1 screening methods in BC in the near future via increasing the accuracy of criteria for further genetic evaluation.

Assessment of Pain, Acceptance of Illness, Adjustment to Life, and Strategies of Coping with Illness among Patients with Gastric Cancer.

Gastric cancer is the fourth leading cause of deaths in Poland. The standard treatment for non-advanced gastric cancer is surgery, which significantly reduces the quality of life of patients. The objective of the study was to evaluate the strategy of coping with pain and its control, acceptance of illness, and adjustment to living with cancer in patients suffering from gastric cancer. The analysis of the impact of socio-economic factors on the above-mentioned problems was also analyzed. The study was conducted among 93 patients diagnosed with gastric cancer, treated on an outpatient basis at the Oncology Center-Maria Sklodowska-Curie Institute in Warsaw in 2017-2018. The PAPI (paper and pencil interview) technique was used. The questionnaire interview included metric questions (socio-economic variables) and four psychometric tests: BPCQ (the Beliefs about Pain Control Questionnaire), CSQ (the Pain Coping Strategies Questionnaire), AIS (Acceptance of Illness Scale), and Mini-MAC (Mental Adjustment to Cancer) test. In the area of pain control, patients with gastric cancer assign the greatest role to internal factors (M = 16.34, SD = 4.93), although women obtained the highest value in the impact of physicians. In the area of coping with pain, patients most likely select the strategy of praying/hoping (M = 22.19, SD = 9.36). The mean value of acceptance of illness for patients with gastric cancer is M = 24.02, SD = 7.69, and it is not conditioned by any socio-economic variable. In the area of mental adjustment to illness, the highest values were obtained by positive reevaluation (M = 20.73, SD = 3.35) and fighting spirit (M = 20.68, SD = 3.98). Patients with gastric cancer control pain mainly through internal factors. The most frequently chosen strategy for coping with pain is praying/hoping, and positive reevaluation prevails in the field of mental adjustment. The results point to specific factors that can affect the patient's pain, quality of life, and treatment outcomes. Knowing the diversity of these factors, it is possible to plan specific psychotherapeutic activities for specific groups of people that could be a supplement to the standard treatment process.

Refusal to Take Sick Leave after Being Diagnosed with a Communicable Disease as an Estimate of the Phenomenon of Presenteeism in Poland.

OBJECTIVE: The purpose of this study was to estimate the prevalence of presenteeism in patients with communicable diseases in Poland. SUBJECT AND METHODS: This study was based on data from the medical records of 2,529 patients aged 19-64 years. All of the patients were diagnosed with communicable diseases. The inclusion criteria were based on implementing decision concerning communicable diseases made by the Commission of the European Union. Associations between refusal to take sick leave and patients' age, gender, and diagnosis in terms of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) were tested. Linear regression analysis of the data acquired from the patients who agreed to take sick leave was further used to estimate the possible length of sick leave in patients who refused to take it. RESULTS: The number of patients who refused to take sick leave was 18.1%. The presenteeism rate was related to the age of patients (periods of sick leave were longer in older patients) and the ICD-10 diagnosis (largely in bacterial intestinal infections and measles). The estimated number of days spent on sick leave in patients who refused to take it, assuming that they made a different decision and complied with it, was in the range of 4-6 days. CONCLUSION: The prevalence of presenteeism in the case of communicable diseases in Poland is lower than in the general population. However, as the refusals to take sick leave took place in the case of potentially contagious diseases, the negative impact on productivity may be significant.

Carbon footprint of inhalers in COPD therapy in 2018 and 2019 in Poland in response to the Kigali amendment.

The treatment of patients with obstructive airway diseases is based on the use of inhalation preparations. Some of them, mainly including pressurized metered dose inhalers (pMDIs), contain compressed gases - hydrofluoroalkanes, which generate carbon dioxide emissions, creating the so-called carbon footprint. AIM: The aim of the study was to evaluate the consumption of individual active substances, the types of inhalers used and calculation of the carbon footprint of popular therapies in 2018 and 2019 in Poland. MATERIALS AND METHODS: The ratio of pMDI vs DPI (dry powder inhaler) data and the data on using long-acting ß2-agonists (LABAs), shortacting muscarinic antagonists (SAMAs), long-acting muscarinic antagonists (LAMAs), LAMA+LABAs, LAMA+LABA+ICSs (inhaled corticosteroids) on Polish market during 2018 and 2019 were analyzed. The carbon footprint of such therapies was counted. Then, we studied the reduction of the carbon footprint for scenario A (reducing pMDI by 50%) and scenario B (reducing pMDI by 80%) in the following steps of analysis. RESULTS: The general structure of pMDI/DPI in Poland in COPD area was not changed in 2019 vs 2018. The carbon footprint is primarily created by pMDI SAMAs. In 2019 in Poland pMDI SAMAs were 1.6 mio units (the same as in 2018), which generated 33.5 kt CO2e annually, but the whole category generates 40.8 kt CO2e. Scenario A gives us a benefit of 18.8 kt CO2e reduction and scenario B brings us a benefit of 29.9 kt CO2e reduction of emissions. CONCLUSIONS: Despite Poland's ratification the Kigali amendment did not affect pMDI consumption and did not reduce the carbon footprint. The lower carbon footprint of DPIs should be considered alongside other factors when choosing inhalation devices.

Effect of Geometrical Structure, Drying, and Synthetic Method on Aminated Chitosan-Coated Magnetic Nanoparticles Utility for HSA Effective Immobilization.

Human serum albumin (HSA) is one of the most frequently immobilized proteins on the surface of carriers, including magnetic nanoparticles. This is because the drug-HSA interaction study is one of the basic pharmacokinetic parameters determined for drugs. In spite of many works describing the immobilization of HSA and the binding of active substances, research describing the influence of the used support on the effectiveness of immobilization is missing. There are also no reports about the effect of the support drying method on the effectiveness of protein immobilization. This paper examines the effect of both the method of functionalizing the polymer coating covering magnetic nanoparticles (MNPs), and the drying methods for the immobilization of HSA. Albumin was immobilized on three types of aminated chitosan-coated nanoparticles with a different content of amino groups long distanced from the surface Fe3O4-CS-Et(NH2)1-3. The obtained results showed that both the synthesis method and the method of drying nanoparticles have a large impact on the effectiveness of immobilization. Due to the fact that the results obtained for Fe3O4-CS-Et(NH2)2 significantly differ from those obtained for the others, the influence of the geometry of the shell structure on the ability to bind HSA was also explained by molecular dynamics.

Causes of delays in breast cancer diagnosis in Poland.

Breast cancer is the most common malignant tumor in women. The results of breast cancer treatment to a large extent depend on the time of the primary diagnosis of the disease. AIM: The aim of this study was to determine the most common causes of the delay and the delay time in the diagnosis of breast cancer in Polish women. MATERIALS AND METHODS: The study was performed using a diagnostic survey and analysis of medical documentation from the Subcarpathian Regional Oncology Center, Poland. A total of 231 patients with diagnosed breast cancer were recruited to the study. RESULTS: Delays in diagnosing of breast cancer were found in 83.1% of all the patients. The average time from the first symptom observation by a woman to the first medical consultation was on average 61.7 days. The most common cause of the delay in medical consultation in the examined group was a fear of diagnosing cancer (31.2%). CONCLUSIONS: The examined women require permanent health education in the field of breast cancer and the importance of early diagnosis of the disease for the effectiveness of treatment and prognosis.

Bis(Cyclic Alkyl Amino Carbene) Ruthenium Complexes: A Versatile, Highly Efficient Tool for Olefin Metathesis.

The state-of-the-art in olefin metathesis is application of N-heterocyclic carbene (NHC)-containing ruthenium alkylidenes for the formation of internal C=C bonds and of cyclic alkyl amino carbene (CAAC)-containing ruthenium benzylidenes in the production of terminal olefins. A straightforward synthesis of bis(CAAC)Ru indenylidene complexes, which are highly effective in the formation of both terminal and internal C=C bonds at loadings as low as 1 ppm, is now reported.

Immunohistochemical characteristics of basal-like breast cancer.

Basal-like breast cancer (BLBC) occurs mainly in young patients. It is characterized by an aggressive clinical outcome, presence of distant metastases, particularly within the first five years of the disease, bad prognosis and relatively high mortality. Recently greater interest of scientists in this subtype of breast cancer has been observed. Despite such many well-known potential biomarkers of BLBC, currently there is no official international panel of antigens dedicated to diagnosis of this subtype of breast cancer. The most commonly used set in this case contains four antibodies - estrogen receptor (ER), epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) and cytokeratins (CK) 5/6 - although it cannot provide one hundred percent detectability of these lesions. Incorporation of additional biomarkers into a panel can increase specificity, at the potential cost of sensitivity. Many biomarkers have been associated with the basal-like phenotype, and those with high sensitivity and/or specificity could improve the performance of immunohistochemical surrogate panels. Work on detection of the best of them is constantly being performed.

Enantioselective Synthesis of Chromanones Bearing Quaternary Substituted Stereocenters Catalyzed by (1R)-Camphor-Derived N-Heterocyclic Carbenes.

A catalytic asymmetric intramolecular crossed-benzoin reaction for the synthesis of chromanones by novel camphor-derived N-heterocyclic carbenes is described. The corresponding chromanones bearing quaternary stereogenic centers were isolated in high yields with high to excellent enantioselectivity.

Hypoxia in breast cancer.

Breast cancer continues to be one of the most common malignancies and is a serious problem particularly in women, although men may also be affected. Such lesions are commonly accompanied by hypoxia, and therefore hypoxia-dependent mechanisms, such as overexpression of hypoxia-inducible factor (HIF), the mechanisms are studied as part of the search for a novel method of cancer treatment. Blocking the activity of HIF and HIF-dependent molecular changes raises hopes for identification of a molecular target to inhibit the tumor growth or even to completely prevent its progression. However, this is difficult due to the crucial role HIF plays in numerous processes occurring not only in cancer cells but mostly in healthy systemic cells in physiological conditions.

HLA-B27 detection - comparison of genetic sequence-based method and flow cytometry assay.

OBJECTIVES: The presence of human leukocyte antigen B27 (HLA-B27) is strongly associated with ankylosing spondylitis. HLA-B27 testing is routinely applied in the diagnosis of this disease. The aim of the present study was to compare two methods of HLA-B27 detection - a genetic sequence-based method and a flow cytometry assay. MATERIAL AND METHODS: Peripheral blood was obtained from 300 individuals with suspected spondyloarthropathy. Expression of HLA-B27 on the T cell surface was analysed by flow cytometry assay using GS145.2 monoclonal antibody specific for HLA-B27. DNA was isolated from the whole blood. Genes coding for HLA-B27, -B40 and -B47:01 were detected by polymerase chain reaction using the MW02/MW09 primer pair. Then, positive samples were sequenced in order to discriminate allelic variations of the HLA-B27 gene. Results of sequencing were analysed using Chromas LITE 2.1.1 software, BLAST software and the IMGT/HLA database. Ambiguous samples were additionally analysed by polymerase chain reaction using E91 and E136 primers amplifying a 135-bp fragment of the human HLA-B27 gene. RESULTS: Among 300 samples, 76 were HLA-B27-positive on the basis of flow cytometry analysis. Genetic sequence analysis confirmed positivity of 73 from among 76 samples. Two hundred twenty six samples were HLA-B27-negative, whereas the result of one sample analysis was ambiguous. Fifty-three samples were identified as allelic variation 27:05, 19 samples as allelic variation 27:02, and one sample as allelic variation 27:07. CONCLUSIONS: This study shows that the genetic sequence-based method and the flow cytometry assay give consistent results in 99% of cases. The performed genetic analysis proves that the majority of HLA-B27-positive samples belong to the 27:05 allelic variation, which is strongly associated with high risk of ankylosing spondylitis.

The role of oestrogen and progesterone receptors in breast cancer - immunohistochemical evaluation of oestrogen and progesterone receptor expression in invasive breast cancer in women.

AIM OF THE STUDY: Expression of oestrogen and progesterone receptors is a very powerful and useful predictor. Because the response rate to hormonal treatment in breast cancer is associated with the presence of oestrogen and progesterone receptors, assessment of the receptor expression profile allows for prediction of breast cancer response to hormonal treatment. The aim of this study was to assess whether the expression of receptors for oestrogen (ER) and progesterone (PR) in the tumour tissue of patients with invasive breast cancer correlated with tumour histological type, histological grade of malignancy, tumour size, and lymph node status. MATERIAL AND METHODS: Materials consisted of histological preparations derived from patients treated for invasive breast cancer. Evaluations were conducted with histopathological and immunohistochemical methods using suitable antibodies. RESULTS: Among 231 cases of breast cancer 18 invasive lobular carcinomas (ILC) and 213 invasive ductal carcinomas (IDC) were diagnosed. Taking the histological type of tumour into account, oestrogen receptor-positive reaction was observed in 74.2% of IDC and 77.8% of ILC, and the positive response to PR was observed in 67.1% of IDC and 61.1% of ILC. Considering the histological grade, ER- in the largest percentage (72%) was observed in second-grade (G2) invasive carcinomas. Similarly, PR expression (75%) was found in the largest percentage in second-grade (G2) carcinomas. Based on our own studies and data from literature, it appears that the ER (+) status is an indicator of good prognosis, because it points to a less aggressive cancer, in which overall survival and disease-free time is longer in comparison with ER (-) tumours. CONCLUSIONS: Determination of ER status may, therefore, have significant clinical value and is widely used in routine pathological diagnostics.