Kodeks etyki zawodowej w rachunkowości jako przykład zbioru zasad etycznego postępowania w zawodzie księgowego

Sponsorami konferencji byli: Stowarzyszenie Księgowych w Polsce Oddział Okręgowy w Łodzi, Krajowa Izba Biegłych Rewidentów

Identification and characterization of mutations in ubiquitin required for non-covalent dimer formation

Ubiquitin (Ub) is a small protein that post-translationally modifies a variety of substrates in eukaryotic cells to modulate substrate function. The ability of Ub to interact with numerous protein domains makes Ub an attractive scaffold for engineering ubiquitin variants (UbVs) with high target specificity. Previously, we identified a UbV that formed a non-covalent stable dimer via a β-strand exchange, and in the current work we identified and characterized the minimal substitutions in the primary sequence of Ub required to form a higher ordered complex. Using solution angle scattering and X-ray crystallography, we show that a single substitution of residue Gly10 to either Ala or Val is sufficient to convert Ub from a monomer to a dimer. We also investigate contributions to dimer formation by the residues in the surrounding sequence. These results can be used to develop next-generation phage-display libraries of UbVs to engineer new interfaces for protein recognition

Modelling of long term low water level in mountain river catchments area

Changing atmospheric conditions, including above all the deepening extreme weather phenomena, are increasing from year to year. This, in consequence, causes an increase in the incidence of low outflows. The study compares low water levels for two catchments: Biała Woda and Czarna Woda, and phosphorus and nitrogen load using the Nutrient Delivery Ratio (NDR) model in InVEST software. The objective of the NDR is to map nutrient sources from catchment area and transfer to the river bed. The nutrient loads (nitrogen and phosphorus) spread across the landscape are determined based on a land use (LULC) map and associated loading rates described in literature. The studies have shown that low water levels have been more common recently and pose the greatest threat to the biological life in the aquatic ecosystems. The structure of land use is also of great importance, with a significant impact on the runoff and nitrogen and phosphorus load. Phosphorus and runoff from surface sources to the water of Biała Woda and Czarna Woda catchments area has been reduced in forested areas. Only higher run-offs are observed in the residential buildings zone. The nitrogen load was also greater in the lower (estuary) parts of both catchments, where residential buildings dominate.info:eu-repo/semantics/publishedVersio

Wartość prognostyczna scyntygrafii perfuzyjnej mięśnia sercowego metodą SPECT z użyciem 99mTc-MIBI w grupie pacjentów po przebytym w przeszłości zawale serca

Introduction. Data describing prognostic utility of SPECT (single-photon emission computed tomography) among patients with history of myocardial infarction (MI) is scarce. We aimed to compare prognostic value of SPECT scans in patients with vs. without history of myocardial infarction (MI) prior to perfusion imaging. Material and methods. 151 consecutive patients with history of myocardial infarction, who underwent exercise 99mTc-MIBI SPECT examination were enrolled in the study (group 1). Next, based on clinical and demographic baseline characteristics, SPECT result and duration of follow-up period, a matching control subgroup (group 2) of 151 patients without history of MI was formed. During a mean follow-up of 60 ± 15 months in group 1 and a mean follow-up of 60 ± 13.5 months in group 2, we analyzed prevalence of cardiovascular events rates (cardiac deaths, myocardial infarctions and cardiac revascularizations). Results. We observed the following rates of cardiac deaths, myocardial infarctions and cardiac revascularizations: 4%, 15% and 26%, respectively in group 1 and 1%, 13% and 17%, respectively in group 2. In patients without history of MI (group 2) presence of mixed perfusion defects on SPECT was associated with significantly higher rate of myocardial infarctions (p = 0.05), hospitalizatons (p = 0.0001) and revascularizations (p = 0.0002). Fixed perfusion defects were associated with significantly higher occurrence of deaths (p = 0.012) and hospitalizations (p = 0.02), but not myocardial infarctions (p = 0.52) or cardiac revascularizations (p = 0.10). In contrast, among patients with history of MI (group 1) there was no statistically significant relationship between any type of perfusion defects and cardiovascular events. Conclusions. Long term follow-up demonstrates that prognostic value of 99mTc-MIBI SPECT is different in patients with and without history of MI.Wstęp. W dostępnej literaturze brakuje badań służących ocenie przydatności prognostycznej scyntygrafii perfuzyjnej mięśnia sercowego SPECT (tomografia emisyjna pojedynczego fotonu) w grupie chorych z wywiadem przebytego zawału serca. Celem opisanego badania jest porównanie wartości prognostycznej SPECT w grupie pacjentów z wywiadem zawału serca przed badaniem SPECT oraz bez takiego wywiadu. Materiał i metody. Do badania włączono 151 kolejnych pacjentów z wywiadem zawału serca, u których wykonano badanie SPECT z użyciem 99mTc-MIBI. Następnie, na podstawie charakterystyki klinicznej i demograficznej oraz długości okresu obserwacji dobrano, grupę kontrolną 151 pacjentów poddanych badaniu SPECT, bez wywiadu wcześniejszego zawału serca. Wyniki. Po średnim okresie obserwacji 60 ± 15 miesięcy (grupa 1) i 60 ± 13,5 miesiąca (grupa 2) częstość wystąpienia punktów końcowych, takich jak zgon z przyczyn sercowo-naczyniowych, zawał serca, rewaskularyzacja, wyniosła odpowiednio 4%, 15% i 26% w grupie 1 oraz 1%, 13%, 17% w grupie 2. Wśród pacjentów bez wywiadu zawału serca (grupa 2) obecność mieszanych zaburzeń perfuzji w badaniu SPECT wiązała się z istotnie większą częstością zawałów serca (p =0,05), hospitalizacji (p = 0,0001) oraz rewaskularyzacji (p = 0,0002). Utrwalone zaburzenia perfuzji wiązały się z istotnie większą liczbą zgonów z przyczyn sercowo-naczyniowych, liczbą hospitalizacji (p=0,02), ale nie zawałów serca (p = 0,52) ani rewaskularyzacji (p = 0,10). Natomiast wśród pacjentów bez wywiadu zawału serca (grupa 1) nie zaobserwowano istotnej statystycznie zależności między typem zaburzeń perfuzji a występowaniem powyższych punktów końcowych. Wnioski. W długoterminowej obserwacji wykazano różnicę w zakresie wartości rokowniczej badania SPECT między pacjentami po przebytym zawale serca oraz bez wywiadu zawału

Acute retinal pigment epithelitis in a 11-year-old child: case presentation and follow-up using optical coherence tomography angiography and static visual field

We present a case of unilateral self-limiting acute retinal pigment epithelitis (ARPE) in an 11-year-old girl and 10 weeks of follow-up until complete recovery using spectral domain optical coherence tomography (SD-OCT), SD-OCT-angiography (SD-OCTA) and static visual field

LIM kinase inhibitors disrupt mitotic microtubule organization and impair tumor cell proliferation

The actin and microtubule cytoskeletons are critically important for cancer cell proliferation, and drugs that target microtubules are widely-used cancer therapies. However, their utility is compromised by toxicities due to dose and exposure. To overcome these issues, we characterized how inhibition of the actin and microtubule cytoskeleton regulatory LIM kinases could be used in drug combinations to increase efficacy. A previously-described LIMK inhibitor (LIMKi) induced dose-dependent microtubule alterations that resulted in significant mitotic defects, and increased the cytotoxic potency of microtubule polymerization inhibitors. By combining LIMKi with 366 compounds from the GSK Published Kinase Inhibitor Set, effective combinations were identified with kinase inhibitors including EGFR, p38 and Raf. These findings encouraged a drug discovery effort that led to development of CRT0105446 and CRT0105950, which potently block LIMK1 and LIMK2 activity in vitro, and inhibit cofilin phosphorylation and increase αTubulin acetylation in cells. CRT0105446 and CRT0105950 were screened against 656 cancer cell lines, and rhabdomyosarcoma, neuroblastoma and kidney cancer cells were identified as significantly sensitive to both LIMK inhibitors. These large-scale screens have identified effective LIMK inhibitor drug combinations and sensitive cancer types. In addition, the LIMK inhibitory compounds CRT0105446 and CRT0105950 will enable further development of LIMK-targeted cancer therapy

Correlation between isotherms and isodoses in breast cancer radiotherapy - first study

The study is focused on correlation of isotherms derived from thermal images with an isodoses describing treatment plan for patients with breast cancer treated by radiotherapy. The irradiated area covered the part of the body after mastectomy. The study included patients diagnosed with breast cancer who were qualified for radiotherapy treatment. All patients were monitored during each treatment week during the entire radiotherapy process. The measurements were made under strictly defined conditions. In the treatment planning system (TPS), the specific plan was created for each patient. Spatial dose distribution in the patient’s body was obtained and presented by the isodoses (lines connecting points with the same dose values). The following areas from the treatment planning system were plotted on the thermograms: target (tumor area) and isodose: 45 Gy, 40 Gy, 30 Gy, 20 Gy and 10 Gy. The obtained results indicated a high correlation between magnitude of the dose represented as the isodose and the temperature of the treated skin. Moreover, preliminary analysis showed a repeatable increase of the mean temperature in the irradiated area during the treatment

Stabilization of the RAS:PDE6D complex is a novel strategy to inhibit RAS signaling

This work was supported by Cancer Research UK core funding number A17196.RAS is a major anticancer drug target which requires membrane localization to activate downstream signal transduction. The direct inhibition of RAS has proven to be challenging. Here, we present a novel strategy for targeting RAS by stabilizing its interaction with the prenyl-binding protein PDE6D and disrupting its localization. Using rationally designed RAS point mutations, we were able to stabilize the RAS:PDE6D complex by increasing the affinity of RAS for PDE6D, which resulted in the redirection of RAS to the cytoplasm and the primary cilium and inhibition of oncogenic RAS/ERK signaling. We developed an SPR fragment screening and identified fragments that bind at the KRAS:PDE6D interface, as shown through cocrystal structures. Finally, we show that the stoichiometric ratios of KRAS:PDE6D vary in different cell lines, suggesting that the impact of this strategy might be cell-type-dependent. This study forms the foundation from which a potential anticancer small-molecule RAS:PDE6D complex stabilizer could be developed.Publisher PDFPeer reviewe