Evaluation of left ventricular function in overweight children and teenagers with arterial hypertension and white coat hypertension

Background: Obesity in childhood is strongly associated with elevated arterial blood pressure and risk of hypertension. The aim of the study was the evaluation of left ventricular (LV) function in hypertensive and white coat hypertensive overweight children and teenagers. Methods: The study group consisted of 74 overweight patients aged 10.3 ± 3.1 years (range: 6–16 years) diagnosed as hypertensive in standard blood pressure measurement. The control group consisted of 31 normotensive and normoweight children. Ambulatory blood pressure monitoring (ABPM) and echocardiographic assessment of the LV mass and function were performed in all participants. Results: Using ABPM hypertension was confirmed in 20 (27%) children. In the 54 (73%) remaining children white coat hypertension was diagnosed. The analysis of echocardiographic parameters revealed higher LV mass index (LVMI) in hypertensive overweight than in normotensive normoweight children (47.5 ± 9.2 g/m2.7 vs. 39.8 ± 12.1 g/m2.7; p < 0.05) and no difference between overweight hypertensive and white coat hypertension-hypertensive groups. The deceleration time of mitral early filling (DCT) was longer in hypertensive normoweight children than in normotensive overweight patients (219.5 ± 110.3 ms vs. 197.8 ± 65.8 ms; p < 0.05). A significant correlation between systolic blood pressure load (SBPL) and DCT (r = 0.57) and moderate correlation between SBPL and LVMI (r: 0.48) as well as between LVMI and isovolumetric relaxation time (r = 0.37) were found. Conclusions: In overweight children the diagnosis of hypertension should be confirmed in ABPM because of the high prevalence of white coat hypertension. Periodic echocardiographic examinations should be recommended in overweight children with increased SBPL and decreased systolic nocturnal deep because of the possibility of LV function impairment

Implementation of Exome Sequencing in Prenatal Diagnosis and Impact on Genetic Counseling: The Polish Experience

This article belongs to the Special Issue Novel Insights into Prenatal Genetic Testing.Background: Despite advances in routine prenatal cytogenetic testing, most anomalous fetuses remain without a genetic diagnosis. Exome sequencing (ES) is a molecular technique that identifies sequence variants across protein-coding regions and is now increasingly used in clinical practice. Fetal phenotypes differ from postnatal and, therefore, prenatal ES interpretation requires a large amount of data deriving from prenatal testing. The aim of our study was to present initial results of the implementation of ES to prenatal diagnosis in Polish patients and to discuss its possible clinical impact on genetic counseling. Methods: In this study we performed a retrospective review of all fetal samples referred to our laboratory for ES from cooperating centers between January 2017 and June 2021. Results: During the study period 122 fetuses were subjected to ES at our institution. There were 52 abnormal ES results: 31 in the group of fetuses with a single organ system anomaly and 21 in the group of fetuses with multisystem anomalies. The difference between groups was not statistically significant. There were 57 different pathogenic or likely pathogenic variants reported in 33 different genes. The most common were missense variants. In 17 cases the molecular diagnosis had an actual clinical impact on subsequent pregnancies or other family members. Conclusions: Exome sequencing increases the detection rate in fetuses with structural anomalies and improves genetic counseling for both the affected couple and their relatives.This research was funded by the Ministry of Health, granted to the Center of Postgradu- ate Medical Education, Poland, grant number Minigrant-501-1-106-44-20/MG4 to J.B., and by the National Science Centre, Poland, grant number Miniatura 2—Dec2018/02/X/NZ2/00709 to D.M.info:eu-repo/semantics/publishedVersio

The demographic challenges for the mazovian regional authority

Artykuł prezentuje wybrane zagadnienia dotyczące zmian demograficznych w województwie mazowieckim. Sytuacja demograficzna Mazowsza jest powiązana z polaryzacją jego rozwoju powodującą zróżnicowania przestrzenne problemów społecznych. Dlatego w pierwszej części artykułu zaprezentowano podstawowe cechy rozwoju społeczno-gospodarczego województwa mazowieckiego oraz wskazano główne trendy w rozwoju demograficznym regionu tj.: a) spadek zachowań promałżeńskich i prokreacyjnych, b) depopulację obszarów peryferyjnych, c) starzenie się ludności. Odwrócenie tych zjawisk wymaga zdecydowanej reakcji rządu i władz województwa mazowieckiego. W drugiej części zaprezentowano przewidziane w „Strategii rozwoju województwa mazowieckiego do roku 2030. Innowacyjne Mazowsze” oraz w „Strategii Polityki Społecznej Województwa Mazowieckiego na lata 2014-2020” działania na rzecz powstrzymania i zapobiegania negatywnym trendom rozwoju społecznego.The article presents selected issues of demographic change in the Mazowieckie Voivodship. Demographic situation is related to the polarization of its development, resulting in spatial differentiation of social problems. Therefore, in the first part of the article presents the basic features of the socio-economic development Mazowieckie Voivodship are presented and the main trends in the demographic development of the region are identified, such as: a) a decrease in marital and reproductive behaviors, b) the depopulation of peripheral areas, c) the aging of the population. These phenomena requires a strong response from the government and the regional authority. "The Development Strategy for the Mazowieckie Voivodship 2030. Innovative Mazowsze" and "The Strategy of Social Policy of the Mazowieckie Voivodship 2014- 2020" includes actions to stop and prevent the negative trends of social development

Thermodynamics parameters for binding of halogenated benzotriazole inhibitors of human protein kinase CK2α.

The interaction of human CK2α (hCK2α) with nine halogenated benzotriazoles, TBBt and its analogues representing all possible patterns of halogenation on the benzene ring of benzotriazole, was studied by biophysical methods. Thermal stability of protein-ligand complexes, monitored by calorimetric (DSC) and optical (DSF) methods, showed that the increase in the mid-point temperature for unfolding of protein-ligand complexes (i.e. potency of ligand binding to hCK2α) follow the inhibitory activities determined by biochemical assays. The dissociation constant for the ATP-hCK2α complex was estimated with the aid of microscale thermophoresis (MST) as 4.3±1.8μM, and MST-derived dissociation constants determined for halogenated benzotriazoles, when converted according to known ATP concentrations, perfectly reconstruct IC50 values determined by the biochemical assays. Ligand-dependent quenching of tyrosine fluorescence, together with molecular modeling and DSC-derived heats of unfolding, support the hypothesis that halogenated benzotriazoles bind in at least two alternative orientations, and those that are efficient hCK2α inhibitors bind in the orientation which TBBt adopts in its complex with maize CK2α. DSC-derived apparent heat for ligand binding (ΔΔHbind) is driven by intermolecular electrostatic interactions between Lys68 and the triazole ring of the ligand, as indicated by a good correlation between ΔΔHbind and ligand pKa. Overall results, additionally supported by molecular modeling, confirm that a balance of hydrophobic and electrostatic interactions contribute predominantly (~40kJ/mol), relative to possible intermolecular halogen/hydrogen bonding (less than 10kJ/mol), in binding of halogenated benzotriazoles to the ATP-binding site of hCK2α. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases

Wpływ wyników badań naukowych na formułowanie polityki rozwojowej w oparciu o fakty – przykład projektu Trendy rozwojowe Mazowsza

Evidence-based policies require data and information on determinants, trends, and consequences of ongoing development processes. This data and information must be conveyed to policy makers. Thus a mechanism is needed to reach them and equip them with arguments for or against specific policy options. This mechanism is to be incorporated into the system of monitoring, analyzing, planning, and managing development processes. This article presents a brief outline of how the project “Development Trends of Mazovian Region” (DTMR) implemented in the years 2009-20014 related to regional policy formulation in terms of building an information base for diagnostic purposes, preparing instruments for modeling and scenario building, networking and lobbying for institutional arrangements that would foster cooperation among researchers and practitioners, both planners and policy makers. The DTRM project was co-financed by the European Union under the European Social Fund and managed by the Mazovian Office for Regional Planning.W artykule przedstawiono doświadczenia związane z projektem badawczym „Trendy rozwojowe Mazowsza’, realizowanym przez Mazowieckie Biuro Planowania Regionalnego w Warszawie w latach 2009-2014 oraz omówiono założenia projektu, hipotezy badawcze i organizację badań. Przedstawiono także w skrócie rezultaty diagnozy uwarunkowań i poziomu rozwoju regionu oraz stanu jego zagospodarowania przestrzennego przygotowanej na podstawie wyników badań. W artykule przedstawiono również wyniki weryfikacji hipotez badawczych oraz główne rekomendacje dotyczące działań mających na celu stymulowanie zrównoważonego rozwoju regionu oraz omówiono wykorzystanie wyników badań w przygotowaniu strategicznych dokumentów dotyczących rozwoju regionu: strategii rozwoju województwa, planu zagospodarowania przestrzennego i regionalnej strategii innowacji

Vaccine against African swine fever – where are we and where are we going?

African swine fever (ASF), is a viral disease of pigs and wild boar that is usually deadly. There are neither vaccines nor cures. African swine fever has got a significant negative impact on the global pig industry. The disease control is based on ensuring biosecurity, early diagnosis and culling pig herds with ASFV‐infected animals. However, in view of the ease with which ASFV spreads, its high resistance to environmental conditions and the many difficulties related to the introduction of effective specific immunoprophylaxis, this process is extremely difficult. Despite encountering problems such as lack of an animal model other than the natural host, lack of an effective continuous cell line for the isolation and propagation of ASFV, a risk of reversion to virulence, or inability to differentiate infected animals from vaccinated ones, scientists do not stop trying to design an effective vaccine. Recent approaches to ASF vaccine construction have focused on the development of modified live vaccines by targeted gene deletion from different isolates or of subunit vaccines. Here, we discuss current scientific advances and technological progress in this issue. The design of a safe and effective vaccine against ASFV seems to be achievable, nevertheless, a commercial vaccine is unlikely to appear within the next few years

Spin Probes as Scavengers of Free Radicals in Cells

Spin probes can be used to monitor biological membranes, including the penetration of different molecules into cells. The aim of the present studies was an investigation of the endocytosis process of two spin labels—2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) and 4-hydroxy-TEMPO (TEMPOL)—into yeast cells and a leukemia cell line (HL-60, ATCC CCL-240) by Electron Spin Resonance (ESR). The ESR method is helpful for the direct detection of free radicals. The cell incubation and endocytosis of spin probes were carried out at 310 K. In contrast, the ESR measurements of yeast cells and a leukemia cell line with spin probes were at 240 K. Spectral differentiation was observed; hence, the spin probes present in suspension and attached to the cell membrane could be distinguished. The ESR signal changes of spin probes depended on spin probe concentration, cell number, and type of cell (healthy/cancerous). Additionally, the effect of external factors (oxygen and vitamin C) on the ESR signal decay of spin markers in the cell solution was established. The experimental results prove that the spin probes (TEMPO and TEMPOL) could scavenge free radicals inside the cell. At the same time, the mechanism of spin probe interaction in suspension was determined based on the measurements at low temperatures

Targeting Cellular Trafficking of Fibroblast Growth Factor Receptors as a Strategy for Selective Cancer Treatment

Fibroblast growth factor receptors (FGFRs) in response to fibroblast growth factors (FGFs) transmit signals across the cell membrane, regulating important cellular processes, like differentiation, division, motility, and death. The aberrant activity of FGFRs is often observed in various diseases, especially in cancer. The uncontrolled FGFRs’ function may result from their overproduction, activating mutations, or generation of FGFRs’ fusion proteins. Besides their typical subcellular localization on the cell surface, FGFRs are often found inside the cells, in the nucleus and mitochondria. The intracellular pool of FGFRs utilizes different mechanisms to facilitate cancer cell survival and expansion. In this review, we summarize the current stage of knowledge about the role of FGFRs in oncogenic processes. We focused on the mechanisms of FGFRs’ cellular trafficking—internalization, nuclear translocation, and mitochondrial targeting, as well as their role in carcinogenesis. The subcellular sorting of FGFRs constitutes an attractive target for anti-cancer therapies. The blocking of FGFRs’ nuclear and mitochondrial translocation can lead to the inhibition of cancer invasion. Moreover, the endocytosis of FGFRs can serve as a tool for the efficient and highly selective delivery of drugs into cancer cells overproducing these receptors. Here, we provide up to date examples how the cellular sorting of FGFRs can be hijacked for selective cancer treatment

High Affinity Promotes Internalization of Engineered Antibodies Targeting FGFR1

Fibroblast growth factor receptor 1 (FGFR1) is a plasma membrane protein that transmits signals from the extracellular environment, regulating cell homeostasis and function. Dysregulation of FGFR1 leads to the development of human cancers and noncancerous diseases. Numerous tumors overproduce FGFR1, making this receptor a perspective target for cancer therapies. Antibody-drug conjugates (ADCs) are highly potent and selective anticancer agents. ADCs are composed of antibodies (targeting factors) fused to highly cytotoxic drugs (warheads). The efficiency of ADC strategy largely depends on the internalization of cytotoxic conjugate into cancer cells. Here, we have studied an interplay between affinity of anti-FGFR1 antibodies and efficiency of their cellular uptake. We have developed a unique set of engineered anti-FGFR1 antibodies that bind the same epitope in the extracellular part of FGFR1, but with different affinities. We have demonstrated that these antibodies are effectively taken up by cancer cells in the FGFR1-dependent manner. Interestingly, we have found that efficiency, defined as rate and level of antibody internalization, largely depends on the affinity of engineered antibodies towards FGFR1, as high affinity antibody displays fastest internalization kinetics. Our data may facilitate design of therapeutically relevant targeting molecules for selective treatment of FGFR1 overproducing cancers