Gestational diabetes mellitus (GDM) — do the number of fulfilled diagnostic criteria predict the perinatal outcome?

Objectives: The aim of the study was to check whether the number of fulfilled diagnostic criteria of gestational diabetes mellitus (GDM) had any association with patients’ characteristics and pregnancy outcomes. Material and methods: A total of 756 women with single pregnancies and GDM who gave birth at the 2nd Department of Obstetrics and Gynecology of the Medical University of Warsaw between 01.2013-12.2016 were included in a retrospective analysis. Patients were divided into 2 groups: A - 499 patients diagnosed with GDM on the basis of one diagnostic criterion, B - 257 patients diagnosed with GDM on the basis of more than one diagnostic criterion. Results: Patients from group A had lower pre-pregnancy BMI than those from group B (median 24.9 kg/m2 vs. 26.5 kg/m2, p=0.0003). Women from group A were less frequently treated with insulin than women from group B (19.1% vs. 32.7%; p=0.00002). Group A had lower median OGTT levels than group B (85.9 mg/dL vs. 94.1 mg/dL, p=0,0001; 160.2 mg/dL vs. 197.6 mg/dL, p=0.0001; 144.8 mg/dL vs. 167.0 mg/dL,p=0.0001; respectively). Moreover, in group B the average week of labor was earlier than in group A (mean 38,1 and 38,5 weeks of gestation, p=0,0006). Conclusions: Patients who fulfilled more than one diagnostic criterion for GDM may have worse pregnancy outcome. We think that a number of fulfilled diagnostic criteria for GDM may be an important risk factor for insulin therapy during pregnancy and earlier gestational age at delivery

Dimeric peroxiredoxins are druggable targets in human Burkitt lymphoma

Burkitt lymphoma is a fast-growing tumor derived from germinal center B cells. It is mainly treated with aggressive chemotherapy, therefore novel therapeutic approaches are needed due to treatment toxicity and developing resistance. Disturbance of red-ox homeostasis has recently emerged as an efficient antitumor strategy. Peroxiredoxins (PRDXs) are thioredoxin-family antioxidant enzymes that scavenge cellular peroxides and contribute to red-ox homeostasis. PRDXs are robustly expressed in various malignancies and critically involved in cell proliferation, differentiation and apoptosis. To elucidate potential role of PRDXs in lymphoma, we studied their expression level in B cell-derived primary lymphoma cells as well as in cell lines. We found that PRDX1 and PRDX2 are upregulated in tumor B cells as compared with normal counterparts. Concomitant knockdown of PRDX1 and PRDX2 significantly attenuated the growth rate of lymphoma cells. Furthermore, in human Burkitt lymphoma cell lines, we isolated dimeric 2-cysteine peroxiredoxins as targets for SK053, a novel thiol-specific small-molecule peptidomimetic with antitumor activity. We observed that treatment of lymphoma cells with SK053 triggers formation of covalent PRDX dimers, accumulation of intracellular reactive oxygen species, phosphorylation of ERK1/2 and AKT and leads to cell cycle arrest and apoptosis. Based on site-directed mutagenesis and modeling studies, we propose a mechanism of SK053-mediated PRDX crosslinking, involving double thioalkylation of active site cysteine residues. Altogether, our results suggest that peroxiredoxins are novel therapeutic targets in Burkitt lymphoma and provide the basis for new approaches to the treatment of this disease

Inhibition of protein disulfide isomerase induces differentiation of acute myeloid leukemia cells

Acute myeloid leukemia is a malignant disease of immature myeloid cells. Despite significant therapeutic effects of differentiation-inducing agents in some acute myeloid leukemia subtypes, the disease remains incurable in a large fraction of patients. Here we show that SK053, a thioredoxin inhibitor, induces differentiation and cell death of acute myeloid leukemia cells. Considering that thioredoxin knock-down with short hairpin RNA failed to exert antiproliferative effects in one of the acute myeloid leukemia cell lines, we used a biotin affinity probe-labeling approach to identify potential molecular targets for the effects of SK053. Mass spectrometry of proteins precipitated from acute myeloid leukemia cells incubated with biotinylated SK053 used as a bait revealed protein disulfide isomerase as a potential binding partner for the compound. Biochemical, enzymatic and functional assays using fluorescence lifetime imaging confirmed that SK053 binds to and inhibits the activity of protein disulfide isomerase. Protein disulfide isomerase knockdown with short hairpin RNA was associated with inhibition of cell growth, increased CCAAT enhancer-binding protein α levels, and induction of differentiation of HL-60 cells. Molecular dynamics simulation followed by the covalent docking indicated that SK053 binds to the fourth thioredoxin-like domain of protein disulfide isomerase. Differentiation of myeloid precursor cells requires the activity of CCAAT enhancer-binding protein α, the function of which is impaired in acute myeloid leukemia cells through various mechanisms, including translational block by protein disulfide isomerase. SK053 increased the levels of CCAAT enhancer-binding protein α and upregulated mRNA levels for differentiation-associated genes. Finally, SK053 decreased the survival of blasts and increased the percentage of cells expressing the maturation-associated CD11b marker in primary cells isolated from bone marrow or peripheral blood of patients with acute myeloid leukemia. Collectively, these results provide a proof-of-concept that protein disulfide isomerase inhibition has potential as a therapeutic strategy for the treatment of acute myeloid leukemia and for the development of small-molecule inhibitors of protein disulfide isomerase

Psychological violence against a child as a manifestation of family dysfunctionality

Temat niniejszej pracy to „Przemoc psychiczna wobec dziecka jako przejaw dysfunkcjonalności rodziny”. Jej celem jest zaprezentowanie teoretycznych oraz praktycznych aspektów zjawiska krzywdzenia emocjonalnego wobec osoby nieletniej. Praca składa się z czterech rozdziałów. Pierwszy z nich pełni funkcję wprowadzenia w zakres pracy i przedstawienia jej struktury oraz założeń poznawczych. Rozdział drugi stanowi zbiór informacji na temat rodziny. Zaprezentowane są w nim różne ujęcia definicyjne tej grupy społecznej, funkcje, jakie powinna wypełniać oraz opis zjawiska dysfunkcyjności w rodzinie. Kolejny rozdział to kompendium wiedzy na temat przemocy. Zawiera on opis różnych jej form, specyfikę przemocy psychicznej, a także aspekty prawne oraz badania społeczne dotyczące tego problemu. W rozdziale czwartym znajduje się dokładniejsza charakterystyka znęcania emocjonalnego nad dzieckiem, jego przyczyny oraz skutki. Przedstawione są w nim również różne formy pomocy i wsparcia dla pokrzywdzonych osób – przede wszystkim dzieci. Podsumowanie stanowi konkluzję poruszanych uprzednio zagadnień, będących odpowiedzią na problemy badawcze postawione na wstępie.The subject of this work is "Psychological violence against a child as a manifestation of family dysfunctionality". Its aim is to present the theoretical and practical aspects of the phenomenon of emotional abuse to a minor. The work consists of four chapters. The first of them has a function of introduction to the scope of work and presenting its structure and cognitive assumptions . The second chapter is a collection of information about the family. It presents different definitions of this social group, functions that should be fulfilled and a description of the dysfunctionality in the family . The next chapter is a compendium of knowledge about violence. It contains a description of its various forms, the specificity of psychological Violetce and legal aspects and social research concerning this problem. In the fourth chapter there is a more detailed characteristic of emotional abuse over the child, his causes and effects . There are also presented various forms of assistance and support for victims – especially children. The summary is the conclusion of the previously discussed issues, which are a response to the research problems posed at the beginning

Risk factors of colorectal cancer: the comparison of selected nutritional behaviors of medical and non-medical students

Abstract Background The aim of the study was to compare the diet of medical and non-medical students in relation to colorectal cancer risk factors. Material and methods The study included 239 students of various universities in Bialystok, Poland. Respondents were divided into four groups: students of dietetics at the Medical University (SD), students of other fields of study at the Medical University (SMUB), students of the University of Technology (SBUT) and students of the University of Bialystok (SUB). The research tool was an anonymous questionnaire in an electronic form, designed by the authors of this paper. Results Overweight was the least common among students of dietetics. Products that may increase the risk of developing colorectal cancer were most frequently consumed by students of non-medical universities. Everyday consumption of processed meat products was declared by 2.08% of SD, 24.00% of SMUB, 16.13% of SBUT and 25.93% of SUB. Red meat was consumed several times a week or every day by 25% of SD, 25.33% of SMUB, 48.39% of SBUT and 35.19% of SUB. Fast-food meals consumption once or several times a week was confirmed by 4.17% of SD, 18.67% of SMUB, 27.42% of SBUT and 38.89% of SUB. Conclusion The study conducted shows that students expose themselves to colorectal cancer risk factors through their diet

Umiejscowienie kontroli zdrowia wśród leśników i myśliwych wobec zawodowej ekspozycji na choroby przenoszone przez kleszcze

Introduction: Making the forester profession and practicing hunting associate with frequent staying in the environment of feeding ticks and exposure to biological agents. Lyme disease and encephalitis transmitted by ticks are the most frequently diagnosed tick-borne diseases in Poland. In order to avoid the infection it’s important to use before exposure prophylaxis and take appropriate actions after the bite of a tick.Aim: To assess the degree of exposure to tick-borne diseases in the group of foresters and hunters against the Multidimensional Health Locus of Control Scale (MHLC).Material and methods: The study group consisted of 121 persons: 66 foresters, 15 hunters and 40 respondents who are both forester and hunter. The study used diagnostic survey method using: the own questionnaire and MHLC Scale.Results: Foresters and hunters are exposed to tick-borne diseases. As many as 55.86% respondents were stabbed by a tick from 1-10 times in the last year. Among 45.59% (n=51) of the foresters and hunters tick-borne diseases were detected: it was Lyme disease in 50 cases and tick-borne encephalitis in one. Most respondents knew personal protection methods in the prevention of infection and they applied to those methods. However, the number of stings by ticks wasn’t dependent on the actions and taken precautions.Conclusions: The types of locus of health control hadn’t connection with the activities undertaken by the foresters and hunters after a tick. In the diagnosis of diseases transmitted by ticks essential role has post-exposure observation of the body.    Wstęp. Wykonywanie zawodu leśnika oraz uprawianie myślistwa wiążą się z częstym przebywaniem w środowisku żerowania kleszczy i narażeniem na czynniki biologiczne. Borelioza z Lyme i zapalenie mózgu przenoszone przez kleszcze stanowią najczęściej rozpoznawane choroby odkleszczowe w Polsce. Cel pracy. Ocena stopnia ekspozycji na choroby przenoszone przez kleszcze w grupie leśników i myśliwych na tle wielowymiarowej skali umiejscowienia kontroli zdrowia. Materiał i metody. Grupę badaną stanowiło 121 osób: 66 leśników, 15 myśliwych oraz 40 respondentów będących jednocześnie leśnikiem i myśliwym. W badaniu zastosowano metodę sondażu diagnostycznego z zastosowaniem autorskiego kwestionariusza ankiety oraz Wielowymiarowej Skali Umiejscowienia Kontroli Zdrowia (MHLC). Wyniki. Leśnicy i myśliwi są narażeni na choroby przenoszone przez kleszcze. Wśród respondentów aż u 55,86% badanych w ostatnim roku miało miejsce 1–10 zakłuć przez kleszcze. Aż u 45,59% (n = 51) respondentów wykryto chorobę odkleszczową: w 50 przypadkach była to borelioza, a w jednym kleszczowe zapalenie mózgu. Badani w większości znali metody ochrony osobistej w profilaktyce zakażenia i stosowali się do nich. Liczba ukłuć przez kleszcze w ich opinii nie była jednak zależna od podejmowanych działań ostrożności. Wnioski. Typy umiejscowienia kontroli zdrowia nie miały związku z działaniami podejmowanymi przez leśników i myśliwych po ukłuciu przez kleszcza. W rozpoznaniu choroby przenoszonej przez kleszcze istotne znaczenie ma obserwacja organizmu po ekspozycji

Coherence-based prediction of Multi-Temporal InSAR measurement availability for infrastructure monitoring

Predicting the availability of measurement points provided by Multi-Temporal Interferometric Synthetic Aperture Radar (MT-InSAR) poses a challenge due to a nonuniform distribution of Persistent Scatterers (PSs). This article introduces a novel method to estimate the availability of MT-InSAR results on buildings and infrastructure networks, eliminating the need for labor-intensive and time-consuming analyses of the entire SAR data stack. The method is based on an analysis of the interferometric coherence decay characteristics and data regarding buildings and transport infrastructure location as inputs to a convolutional neural network. Specifically, a U-Net architecture model was implemented and trained to predict the PS density of Sentinel-1 data. The methodology was applied to a regional-scale analysis of the Dutch infrastructure, resulting in a low 1.06 ± 0.10 mean absolute error in the pixel-based PS count estimation on the test data split, with over 80% of predictions within ± 1 from the actual value. The model achieved high accuracy when applied to a previously unseen dataset, demonstrating strong generalization performance. The proposed workflow, with its notable ability to accurately predict areas lacking measurement points, offers stakeholders a tool to assess the feasibility of applying MT-InSAR for specific structures. Thereby, it enhances infrastructure reliability by addressing a critical need in decision-making processes and improving the applicability of MT-InSAR for structural health monitoring of infrastructure assets

Aptamer and Electrochemical Aptasensor towards Selenate Ions (SeO₄²⁻)

Selenium is an essential inorganic compound in human and animal nutrition, involved in the proper functioning of the body. As a micronutrient, it actively contributes to the regulation of various metabolic activities, i.e., thyroid hormone, and protection against oxidative stress. However, Se exhibits a narrow concentration window between having a positive effect and exerting a toxic effect. In higher doses, it negatively affects living organisms and causes DNA damage through the formation of free radicals. Increased reactivity of Se anions can also disrupt the integrity and function of DNA-repairing proteins. As the permissible concentration of Se in drinking water is 10 µg/L, it is vital to develop sensitive and robust methods of Se detection in aqueous samples. In this study, for the first time, we proposed a selective aptamer for selenate ion detection, chosen following the SELEX process, and its application in the construction of an electrochemical aptasensor towards SeO42− ions. Measurement conditions such as the used redox marker and pH value of the measurement solution were chosen. The proposed aptasensor is characterized by good selectivity and an LOD of 1 nM. Conditions for biosensor regeneration and storage were also investigated in this research

N-glycosylation acts as a switch for FGFR1 trafficking between the plasma membrane and nuclear envelope

Abstract Fibroblast growth factor receptor 1 (FGFR1) is a heavily N-glycosylated cell surface receptor tyrosine kinase that transmits signals across the plasma membrane, in response to fibroblast growth factors (FGFs). Balanced FGF/FGFR1 signaling is crucial for the development and homeostasis of the human body, and aberrant FGFR1 is frequently observed in various cancers. In addition to its predominant localization to the plasma membrane, FGFR1 has also been detected inside cells, mainly in the nuclear lumen, where it modulates gene expression. However, the exact mechanism of FGFR1 nuclear transport is still unknown. In this study, we generated a glycosylation-free mutant of FGFR1, FGFR1.GF, and demonstrated that it is localized primarily to the nuclear envelope. We show that reintroducing N-glycans into the D3 domain cannot redirect FGFR1 to the plasma membrane or exclude the receptor from the nuclear envelope. Reestablishment of D2 domain N-glycans largely inhibits FGFR1 accumulation in the nuclear envelope, but the receptor continues to accumulate inside the cell, mainly in the ER. Only the simultaneous presence of N-glycans of the D2 and D3 domains of FGFR1 promotes efficient transport of FGFR1 to the plasma membrane. We demonstrate that while disturbed FGFR1 folding results in partial FGFR1 accumulation in the ER, impaired FGFR1 secretion drives FGFR1 trafficking to the nuclear envelope. Intracellular FGFR1.GF displays a high level of autoactivation, suggesting the presence of nuclear FGFR1 signaling, which is independent of FGF. Using mass spectrometry and proximity ligation assay, we identified novel binding partners of the nuclear envelope-localized FGFR1, providing insights into its cellular functions. Collectively, our data define N-glycosylation of FGFR1 as an important regulator of FGFR1 kinase activity and, most importantly, as a switchable signal for FGFR1 trafficking between the nuclear envelope and plasma membrane, which, due to spatial restrictions, shapes FGFR1 interactome and cellular function. Video Abstrac