Assisted reproductive medicine in Poland --Fertility and Sterility Special Interest Group of the Polish Gynaecological Society (SPiN PTG) 2012 report.

OBJECTIVES: The aim of this report is to present data concerning results and complications related to infertility treatment using assisted reproductive technology (ART) and insemination (IUI) in Poland in 2012. MATERIAL AND METHODS: The report was prepared by the Fertility and Sterility Special Interest Group of the Polish Gynaecological Society (SPiN PTG), based on individual data provided by fertility clinics. Reporting was voluntary data were not subject to external verification. The report presents the availability and the structure of infertility treatment services, the number of procedures performed, their effectiveness and the most common complications. RESULTS: In 2014, 34 Polish fertility clinics provided information to the report, presenting data from 2012. The total number of reported treatment cycles using ART was 17,116 (incl. 10,714 fresh IVF/ICSI) and 14,727 IUI. The clinical pregnancy rate per cycle was on average 33.7% for fresh IVF/ICSI and 13.3% for IUI. The prevalence of multiple births was 15.7% and 6.2%, in case of IVF/ICSI and IUI methods respectively The most frequent complication in the course of treatment using ART was ovarian hyperstimulation syndrome (OHSS)--severe OHSS constituted 0.68% of all stimulated cycles. CONCLUSIONS: The SPiN PTG report shows the average effectiveness and safety of ART and was the only proof of responsibility and due diligence of fertility centres in Poland. However, due to the lack of a central register of fertility clinics, facultative participation in the report as well as incomplete information on pregnancy and delivery rate, the collected data do not reflect the full spectrum of Polish reproductive medicine.

[Assisted reproductive medicine in Poland, 2011--SPiN PTG report]. / Medycyna wspomaganego rozrodu w Polsce--raport za rok 2011 Sekcji Plodnosci i Nieplodnosci Polskiego Towarzystwa Ginekologicznego (SPiN PTG).

AIM: The aim of this report is to present data concerning results and complications related to infertility treatment using assisted reproductive technology (ART) and insemination (IUI) in Poland in 2011. MATERIALS AND METHODS: The report was prepared by the Fertility and Sterility Special Interest Group of the Polish Gynaecological Society (SPiN PTG), based on individual data provided by fertility clinics in Poland. Reporting was voluntary and the provided data was not subject to external control. The report presents the availability and the structure of infertility treatment services, the number of procedures performed, their effectiveness and the most common complications. MAIN RESULTS: In 2013, 33 Polish fertility clinics provided information to the SPiN PTG report, presenting data from the year 2011. The total number of reported treatment cycles using ART was 15,340 (incl. 10,011 IVF/ICSI procedures) and 15,627 IUI procedures. The rate of clinical pregnancies in terms of a cycle was 34.2% in case of IVF/ ICSI procedures and 13.4% in case of IUI. The prevalence of multiple births was 20.2% and 8.3% respectively in case of IVF/ICSI and IUI methods. The most frequent complication in the course of treatment using ART was ovarian hyperstimulation syndrome (OHSS). CONCLUSION: The SPiN PTG report allows to find out the average effectiveness and safety of assisted reproduction technologies and is currently the only proof of responsibility and due diligence of fertility centres in Poland. However due to the lack of a central register of fertility clinics, facultative participation in the report as well as incomplete information on pregnancy and delivery the collected data does not reflect the full spectrum of the Polish reproductive medicine.

Unrecognised COVID-19 deaths in central Europe: The importance of cause-of-death certification for the COVID-19 burden assessment.

OBJECTIVE: In Central Europe, the increase in mortality during the COVID-19 pandemic exceeded the number of deaths registered due to coronavirus disease. Excess deaths reported to causes other than COVID-19 may have been due to unrecognised coronavirus disease, the interruptions in care in the overwhelmed health care facilities, or socioeconomic effects of the pandemic and lockdowns. Death certificates provide exhaustive medical information, allowing us to assess the extent of unrecognised COVID-19 deaths. MATERIALS AND METHODS: Data from 187,300 death certificates with a COVID-19 mention from Austria, Bavaria (Germany), Czechia, Lithuania and Poland, 2020-2021, was used. The two step analysis uses Cause of Death Association Indicators (CDAIs) and Contributing CDAIs to identify and measure the statistical strength of associations between COVID-19 and all other medical mentions. RESULTS: 15,700 deaths were reported with COVID-19 only as a contributing condition (comorbidity). In three cases out of four, a typical, statistically significant coronavirus complication or pre-existing condition was registered as the underlying causes of death. In Austria, Bavaria, Czechia and Lithuania the scale of COVID-19 mortality would have been up to 18-27% higher had COVID-19 been coded as the underlying cause of death. Unrecognised coronavirus deaths were equivalent to the entire surplus of excess mortality beyond registered COVID-19 deaths in Austria and the Czech Republic, and its large proportion (25-31%) in Lithuania and Bavaria. CONCLUSIONS: Death certificates with typical coronavirus complications or comorbidities as the underlying causes of death and contributing COVID-19 mentions were plausibly unrecognized coronavirus deaths.

Caddisflies (Trichoptera) of Protected Calcareous Fen Habitats: Assemblages, Environmental Drivers, Indicator Species, and Conservation Issues.

The caddisflies (Trichoptera) of calcareous fen habitats, in contrast to those of other peatland types, have been poorly researched. We thus conducted a two-year study in south-eastern Poland encompassing four types of such habitats-drained and undrained fens and water bodies (pools and ditches) located within the fens-in order to define trichopteran reference assemblages (PCoA), indicator species (IndVal analysis), and the drivers (both natural and those associated with landscape management, including area protection) responsible for caddisfly species distribution (CCA). The most important environmental driver was habitat persistence. Distance-based RDA analysis revealed a distinct pattern in the distribution of species with or without diapause along the persistence gradient. Environmental drivers associated with plants were also crucial for both fens and water bodies. The key factor influencing the caddisfly assemblages of pools and ditches was the use and management of the surrounding land, whereas in the fens, it was the level of area protection. Physical and chemical water parameters had no statistically significant impact on the assemblages. Some factors can be modified by humans (e.g., water level regulation, vegetation, and landscape management) to maintain healthy ecosystems for aquatic insects.

Assessment of the Actual Toxicity of Engine Exhaust Gas Emissions from Euro 3 and Euro 6 Compliant Vehicles with the BAT-CELL Method Using In Vitro Tests.

Legal restrictions on vehicle engine exhaust gas emission control do not always go hand in hand with an actual reduction in the emissions of toxins into the atmosphere. Moreover, the methods currently used to measure exhaust gas emissions do not give unambiguous results on the impact of the tested gases on living organisms. The method used to assess the actual toxicity of gases, BAT-CELL Bio-Ambient-Tests using in vitro tests, takes into account synergistic interactions of individual components of a mixture of gases without the need to know its qualitative and quantitative composition and allows for determination of the actual toxicity of the gas composition. Using the BAT-CELL method, exhaust gases from passenger vehicles equipped with spark-ignition engines complying with the Euro 3 and Euro 6 emission standards were tested. The results of toxicological tests were correlated with the results of chromatographic analysis. It was shown that diverse qualitative composition of the mixture of hydrocarbons determining the exhaust gases toxicity may decrease the percentage value of cell survival. Additionally, it was proven that the average survival of cells after exposure to exhaust gases from tested vehicles meeting the more restrictive Euro 6 standard was lower than for vehicles meeting the Euro 3 standard thus indicating the higher toxicity of exhaust gases from newer vehicles.

Assisted reproductive medicine in Poland, 2013-2016: Polish Society of Reproductive Medicine and Embryology (PTMRiE) and Fertility and Sterility Special Interest Group of the Polish Society of Gynaecologists and Obstetricians (SPiN PTGiP) report.

OBJECTIVES: The purpose of this publication is to present data on the results and complications associated with infertility treatment using assisted reproductive technology (ART) and intrauterine insemination (IUI) in Poland between 2013 and 2016. MATERIAL AND METHODS: The report was prepared by the Polish Society of Reproductive Medicine and Embryology (PTMRiE) and the Fertility and Sterility Special Interest Group of the Polish Society of Gynaecologists and Obstetrics (SPiN PTGiP) as a part of the European IVF Monitoring program (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Reporting was voluntary and the data was not subject to external control. The report presents the availability and structure of infertility treatment services, the number of procedures, their effectiveness and complications. RESULTS: Between 2013 and 2016, a total of 106,718 treatment cycles using ART [64,413 classical in vitro fertilization and in vitro fertilization with intracytoplasmic sperm injection (IVF + ICSI), 36,041 frozen embryo replacements (FER)] and 51,405 IUI were recorded. The clinical pregnancy rates per embryo transfer in IVF, ICSI and FER were 38.3%, 38.1% and 32.4%, respectively. The effectiveness of IUI with husband/partner's semen (IUI-H) was 11.1% and with donor semen (IUI-D) 16.7%. Multiple delivery rates were 11.3% and 6.2% in IVF + ICSI and IUI, respectively. The most common complication was the ovarian hyperstimulation syndrome (OHSS) (0.34%). CONCLUSIONS: PTMRiE and SPiN PTGiP report is the only national study documenting Polish reproductive medicine. The results of infertility treatment effectiveness in Poland are comparable with the European data, complications are less frequent than in other countries. The low percentage of multiple pregnancies, and so perinatal complications, is especially valuable. However, due to the lack of a central database and register, the possibility of external control and monitoring of pregnancies and births is limited. Thus, a fully reliable assessment of the treatment quality in our country is not possible.

[Polymorphisms in the oxidative stress-related genes and cancer risk]. / Polimorfizm genów obrony antyoksydacyjnej a ryzyko rozwoju raka.

Oxidative damage induced by the generation of reactive oxygen species (ROS) is thought to be related to human cancer aetiology. Oxidative stress can result in DNA damage, including oxidized bases, formation of DNA adducts and DNA strand breaks, as well as lipid peroxidation, protein modification, membrane disruption and mitochondrial damage. The effect of reactive oxygen species is balanced by the antioxidant action ofnonenzymatic antioxidants (e.g. vitamins A, C, E, glutathione and flavonoids), as well as antioxidant enzymes. There are three main types of antioxidant defence enzymes: superoxide dismutases, catalase and glutathione peroxidases. A variety of cancer cells are known to have lower antioxidant enzyme activity when compared with their normal counterparts. Many studies have examined genetic variation in the genes coding for these enzymes and their relationship to cancer risk. Only a few genetic variants (single nucleotide polymorphisms--SNPs) in genes related to antioxidant defence were found to be associated with breast, prostate, lung, pancreatic, colorectal and bladder cancer. However, the results from these have been contradictory. Moreover, it is believed that environmental as well as genetic factors are implicated in the development of cancers, and consequently it is important to assess both genetic (including gene-gene association) and non-genetic (e.g. diet, supplementation, smoking and alcohol consumption) variability in the activities of defence enzymes in relation to cancer. In this review we focus on the biological function of antioxidant defence enzymes, and relationship between well-known SNPs in SOD1, SOD2, CAT, GPX1 and GPX4 genes and genetic susceptibility to cancer.

Do BRCA1 modifiers also affect the risk of breast cancer in non-carriers?

We studied whether or not single nucleotide polymorphisms (SNPs), which have been shown to modify the risk of breast cancer in women with a BRCA1 mutation, are associated with cancer risk in unselected (non-hereditary) breast cancer patients. We genotyped seven SNPs in six distinct genes (PHB, RAD51, ITGB3, TGFB1, VEGF, MTHFR) in 1100 unselected Polish breast cancer patients and 1100 controls. The frequencies of genotypes were similar in cases and controls. In a subgroup analysis, we found a positive association between the homozygous genotype PHB 1630C/T and medullary breast cancer (odds ratio (OR)=4.0, 95% confidence interval (CI) 1.1-14.0). PHB 1630C/T was also associated with tumours negative for oestrogen receptor (OR=2.2, 95% CI 1.13-4.4) or progesterone receptor (OR=2.8, 95% CI 1.4-5.8). Our results show that, in general, the single nucleotide polymorphisms which modify the risk of hereditary breast cancer in Poland do not modify the risk of sporadic breast cancer. The PHB 1630 C/T single nucleotide polymorphism was associated with breast cancers with clinical features typical for BRCA1-positive tumours and is deserving of further study.

A structural-dynamical characterization of human Cox17.

Human Cox17 is a key mitochondrial copper chaperone responsible for supplying copper ions, through the assistance of Sco1, Sco2, and Cox11, to cytochrome c oxidase, the terminal enzyme of the mitochondrial energy transducing respiratory chain. A structural and dynamical characterization of human Cox17 in its various functional metallated and redox states is presented here. The NMR solution structure of the partially oxidized Cox17 (Cox17(2S-S)) consists of a coiled coil-helix-coiled coil-helix domain stabilized by two disulfide bonds involving Cys(25)-Cys(54) and Cys(35)-Cys(44), preceded by a flexible and completely unstructured N-terminal tail. In human Cu(I)Cox17(2S-S) the copper(I) ion is coordinated by the sulfurs of Cys(22) and Cys(23), and this is the first example of a Cys-Cys binding motif in copper proteins. Copper(I) binding as well as the formation of a third disulfide involving Cys(22) and Cys(23) cause structural and dynamical changes only restricted to the metal-binding region. Redox properties of the disulfides of human Cox17, here investigated, strongly support the current hypothesis that the unstructured fully reduced Cox17 protein is present in the cytoplasm and enters the intermembrane space (IMS) where is then oxidized by Mia40 to Cox17(2S-S), thus becoming partially structured and trapped into the IMS. Cox17(2S-S) is the functional species in the IMS, it can bind only one copper(I) ion and is then ready to enter the pathway of copper delivery to cytochrome c oxidase. The copper(I) form of Cox17(2S-S) has features specific for copper chaperones.

Structural and dynamic characterization of copper(II) binding of the human prion protein outside the octarepeat region.

Human prion protein (hPrP) fragments encompassing the 91-120 region, namely hPrP92-100 (SP1), hPrP106-113 (SP2), hPrP91-120 (LP1), and hPrP91-114 (LP2), were considered for delineation of the Cu(II)-binding site(s). NMR and EPR spectroscopy results obtained from LP1 or LP2 were compared with those obtained from SP1 and SP2. The coexistence of two binding sites, one centered at His96 and the other at His111, was evidenced and ratified by ESI mass spectrometry at low and high metal:peptide ratios. While room-temperature NMR spectroscopy data were consistent with the binding site centered on His111 being approximately fourfold stronger than that centered on His96, low-temperature EPR spectroscopy results yielded evidence for the opposite trend. This disagreement, which has also occurred in the literature, was clarified by temperature-dependent molecular dynamics runs that demonstrated Met112 approaching the metal at room temperature, a process that is expected to stabilize the His111-centered binding site through hydrophobic shielding of the metal coordination sphere.

Copper-ion interaction with the 106-113 domain of the prion protein: a solution-equilibria study on model peptides.

Prion diseases are characterized by a structural modification of the regular prion protein (PrP(C)) to its isoform, termed PrP(Sc)(scrapie). Such a modification involves the secondary and tertiary structure of the protein; the amino acidic sequence remains unchanged. PrP(Sc) is almost insoluble in non-denaturing solvents, resistant to proteases and it loses its redox activity. PrP(C) is able to bind copper and other metal ions: these complexes have been suggested to play an important role in the protein refolding leading to PrP(Sc). It is well-known that at least one relatively strong copper-binding site is located in the PrP(92--126) domain, where two His residues (96 and 111) are present. However, in the same domain, other amino acidic residues bear potentially donating atoms, i.e. Met, Asn and Lys residues. In order to shed light on the role of the side chains of such potentially tridentate amino acids on copper complexation, the polypeptide Ac-KTNMKHMA-NH(2), corresponding to the PrP(106--113) fragment, and some synthetic analogues have been investigated as ligands for the copper ion, by means of both thermodynamic and spectroscopic techniques. The pivotal role of imidazolic side chain of His in "anchoring" the metal ion has been confirmed. On the other hand, no clue was found on the participation of sulfur atom of Met or side amino-group of Lys residues to copper complex-formation.

Identification of a novel high affinity copper binding site in the APP(145-155) fragment of amyloid precursor protein.

The copper(II) binding features of the APP(145-155) and APP(145-157) fragments of the amyloid precursor protein, Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-NH2 and Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-Glu-Thr-NH2 were studied by NMR spectroscopy and NMR findings were supported by UV-vis, CD and EPR spectra. Potentiometric measurements were performed only for the more soluble Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-Glu-Thr-NH2 peptide fragment. The following was shown: (i) the imidazole rings of all the three His residues are involved in metal coordination; (ii) metal binding induces ionisation of Leu-148 and His-149 amide nitrogens that complete the donor set to copper(II) in the species dominant at neutral pH; (iii) the unusual coordination scheme of the His-Xxx-His-Xxx-His consensus sequence justifies the high specificity for Cu(II) when compared to SOD-like or albumin-like peptides or even in amyloid Abeta fragments. The present findings may represent the key for interpreting the observed requirement of His residues conservation for the redox cycling between Cu(II) and Cu(I) by soluble APP.