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This paper focuses on the microstructure and tribological properties of novel hardfacing alloy based on Fe-C-Mn-B doped with Ni, Cr, and Si. The 4 mm-thick coating was deposited on the AISI 1045 carbon steel by the MIG-welding method using flux-cored wires in three passes. The transition zone thickness between the weld layers was ~80 μm, and the width of the substrate-coating interface was 5-10 μm. The following coating constituents were detected: coarser elongated M 2 B borides, finer particles of Cr 7 C 3 carbides, and an Fe-based matrix consisting of ferrite and austenite. The nanohardness of the matrix was ~5-6 GPa, carbides ~16-19 GPa, and borides 22-23 GPa. A high cooling rate during coating fabrication leads to the formation of a fine mesh of M 7 C 3 carbides; borides grow in the direction of heat removal, from the substrate to the friction surface, while in the transition zone, carbides become coarser. The dry sliding friction tests using a tribometer in PoD configuration were carried out at contact pressure 4, 7, 10, and 15 MPa against the AISI 1045 carbon steel (water-quenched and low-tempered, 50-52 HRC). The leading wear phenomenon at 4 and 7 MPa is fatigue, and at 10 and 15 MPa it is oxidation and delamination.

Microfluidics has recently emerged as a powerful tool in generation of submillimeter-sized cell aggregates capable of performing tissue-specific functions, so-called microtissues, for applications in drug testing, regenerative medicine, and cell therapies. In this work, we review the most recent advances in the field, with particular focus on the formulation of cell-encapsulating microgels of small "dimensionalities": "0D" (particles), "1D" (fibers), "2D" (sheets), etc., and with nontrivial internal topologies, typically consisting of multiple compartments loaded with different types of cells and/or biopolymers. Such structures, which we refer to as topological hydrogels or topological microgels (examples including core-shell or Janus microbeads and microfibers, hollow or porous microstructures, or granular hydrogels) can be precisely tailored with high reproducibility and throughput by using microfluidics and used to provide controlled "initial conditions" for cell proliferation and maturation into functional tissue-like microstructures. Microfluidic methods of formulation of topological biomaterials have enabled significant progress in engineering of miniature tissues and organs, such as pancreas, liver, muscle, bone, heart, neural tissue, or vasculature, as well as in fabrication of tailored microenvironments for stem-cell expansion and differentiation, or in cancer modeling, including generation of vascularized tumors for personalized drug testing. We review the available microfluidic fabrication methods by exploiting various cross-linking mechanisms and various routes toward compartmentalization and critically discuss the available tissue-specific applications. Finally, we list the remaining challenges such as simplification of the microfluidic workflow for its widespread use in biomedical research, bench-to-bedside transition including production upscaling, further in vivo validation, generation of more precise organ-like models, as well as incorporation of induced pluripotent stem cells as a step toward clinical applications.

The treatment of children with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL Ph+) is currently unsuccessful. The use of tyrosine kinase inhibitors (TKIs) combined with chemotherapy has modernized ALL Ph+ therapy and appears to improve clinical outcome. We report herein the toxicity events and results of children with ALL Ph+ treated according to the EsPhALL2010 protocol (the European intergroup study of post-induction treatment of Philadelphia chromosome positive ALL) in 15 hemato-oncological centers in Poland between the years 2012 and 2019. The study group included 31 patients, aged 1-18 years, with newly diagnosed ALL Ph+. All patients received TKIs. Imatinib was used in 30 patients, and ponatinib was applied in one child due to T315I and M244V mutation. During therapy, imatinib was replaced with dasatinib in three children. The overall survival of children with ALL Ph+ treated according to the EsPhALL2010 protocol was 74.1% and event-free survival was 54.2% after five years. The cumulative death risk of the study group at five years was estimated at 25.9%, and its cumulative relapse risk was 30%. Our treatment outcomes are still disappointing compared to other reports. Improvements in supportive care and emphasis placed on the determination of minimal residual disease at successive time points, which will impact decisions on therapy, may be required.

The aim of the study was to retrospectively compare the effectiveness of the ALL IC-BFM 2002 and ALL IC-BFM 2009 protocols and the distribution of risk groups by the two protocols after minimal residual disease (MRD) measurement as well as its impact on survival. We reviewed the medical records of 3248 patients aged 1-18 years with newly diagnosed ALL who were treated in 14 hemato-oncological centers between 2002 and 2018 in Poland. The overall survival (OS) of 1872 children with ALL treated with the ALL IC 2002 protocol was 84% after 3 years, whereas the OS of 1376 children with ALL treated with the ALL IC 2009 protocol was 87% (P < 0.001). The corresponding event-free survival rates were 82% and 84% (P = 0.006). Our study shows that the ALL IC-BFM 2009 protocol improved the results of children with ALL compared to the ALL IC-BFM 2002 protocol in Poland. This analysis confirms that MRD marrow assessment on day 15 of treatment by FCM-MRD is an important predictive factor.

Objectives: The aim of this population-based, retrospective study was to analyze biological and clinical features and treatment results in children diagnosed with MPAL in all Polish pediatric oncology centers between 2007 and 2018., Methods: Among 2893 children and adolescents diagnosed and treated for acute leukemia, 39 (1.35%) patients fulfilled the WHO criteria of MPAL. The T/myeloid phenotype was most prevalent., Results: Cytogenetics findings were seen in 2 (5.1%), while chromosomal abnormalities were found in 14 (35.9%) patients. Thirty-two patients achieved CR-1, including 23 (92.0%) treated with ALL-directed chemotherapy and 9 (64.3%) treated with AML-type induction regimens. Within these patients, 4 (12.5%) died due to treatment-related complications and 11 (34.4%) relapsed. Nineteen (63.3%) patients underwent allo-HSCT in CR-1 and 14 (73.7%) of them have been in CR-1. In total, 17 (43.6%) patients remain in CR-1 for 1-12 years, including 14 (58.3%) with T/myeloid MPAL. The 5-year pOS and pEFS were 51.8% and 44.2%, respectively. The overall survival for ALL-directed therapy was significantly better than the one for AML-type chemotherapy (P = .001). It was also better for patients who underwent HSCT in CR-1 (P = .001)., Conclusions: The prognosis of MPAL is unsatisfactory, but initial treatment with ALL-directed chemotherapy consolidated with allo-HSCT improves the outcomes in MPAL., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The aim of this study was to analyse the concentration of reducing sugars in beverages based on apple juice with the addition of 2 and 4% of native and high polymerized inulin as well as oligofructose. Moreover, the effect of the consumption of this potentially prebiotic beverage containing highly polymerized inulin (12 g per 300 mL) on constipation was analysed. Pasteurization of the studied beverages followed by 120-day storage at ambient temperature, carried out in three independent trials, did not cause the hydrolysis of fructans into reducing sugars. Sensory analysis showed that the presence of fructans in beverages based on apple juice did not change the colour, clarity, odour, flavour, sweetness and acidity in comparison to apple juice. A placebo-controlled, randomized study involving 20 volunteers of age 20-29 with symptoms related to chronic constipation showed that the consumption of juice enriched with highly polymerized inulin significantly (p≤ 0.05) increased the frequency of bowel movements and facilitated defecation. The final conclusion is that fructans in beverages based on apple juice are chemically stable, do not affect sensory sensation and can help those with chronic constipation.

The aim of this study was to evaluate the risk factors of relapse and treatment-related deaths in acute lymphoblastic leukemia (ALL) in children residing in Poland.A total of 1872 patients with newly diagnosed ALL, treated according to the ALL IC-BFM 2002 protocol in 14 Polish pediatric hematology centers from 2002 to 2012 were included in the study. Three-hundred eighty-four patients experienced treatment failure. The last follow-up was 31 December, 2016.Univariate analysis identified factors in each risk group that were significantly different between children whose treatment failed and those who remained in the first remission. Multivariate analysis demonstrated that only the age of 10 years or over at primary diagnosis in the high-risk group was an adverse prognostic factor. To facilitate the analysis, patients were divided into three groups: relapsed children who survived; relapsed children who died; children without relapse who died due to toxicity.Our analysis showed that age older than 10 years is a particular risk factor for the failure of first-line of treatment, both in terms of relapse and treatment-related mortality.

Background: Overweight and obesity are a problem negatively affecting human health. Besides the excess of energy from food, development of overweight can also result from food preferences, the frequency of meals and the speed of eating., Objective: The aim of this study was to analyse the effect of eating habits and physical activity on the occurrence of overweight and obesity., Material and Method: The questionnaire survey concerning eating habits and physical activity was conducted among adults aged 20-59 (n=420) in Lublin province (Poland). The subjects were divided into two groups – normal (BMI 18.5-25 kg/m2, n=250) and overweight and obese (BMI≥25 kg/m2, n=170). One-way analysis of variance (ANOVA) and post-hoc Tukey’s test as well as chi-square independence test were applied. In addition, the relative risk of overweight for groups divided according to their habits was determined., Results: The analysis of speed of eating was on the basis of subjective assessment of the subjects and as a relative speed of eating compared to family members and friends. In both methods of assessment, it has been shown that overweight and obesity facilitates fast food intake rate (p=0.0078 and p=0.0010, respectively) The relative risk of obesity and overweight increases almost twice (RR 1.79) when the number of meals consumed daily is between one and two compared to those having five meals a day. In addition, it has been shown that overweight facilitates low physical activity., Conclusions: Slowly consumed meals, high physical activity and having more than two meals a day promotes maintaining a normal body weight., Competing Interests: The authors declare no conflict of interest, (Copyright by the National Institute of Public Health - National Institute of Hygiene)

Background/aim: The risk factors, clinical features and non-hematological toxicity profiles during chemotherapy in acute lymphoblastic leukemia (ALL) patients treated in pediatric hematology centres were analysed., Materials and Methods: A total of 902/1872 children were reported as having grade 3 or 4 toxicity., Results: Among the analysed toxicities, infection and gastrointestinal and liver toxicities were the most common. The median follow-up was 6.8 years. Overall survival and event-free survival rates for the analysed group were lower than those reported for the group without grade ≥3 toxicity. In univariate analysis, we identified the number of toxic episodes, the risk group and remission status that had a significant impact on the outcome. Multivariate analysis demonstrated the risk group and the number of toxic episodes ≥3 to be statistically significant for the results., Conclusion: The toxic profiles investigated in our report should be used in future efforts to decrease the burden of side effects during chemotherapy., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Fiber-based approaches hold great promise for tendon tissue engineering enabling the possibility of manufacturing aligned hydrogel filaments that can guide collagen fiber orientation, thereby providing a biomimetic micro-environment for cell attachment, orientation, migration, and proliferation. In this study, a 3D system composed of cell-laden, highly aligned hydrogel yarns is designed and obtained via wet spinning in order to reproduce the morphology and structure of tendon fascicles. A bioink composed of alginate and gelatin methacryloyl (GelMA) is optimized for spinning and loaded with human bone morrow mesenchymal stem cells (hBM-MSCs). The produced scaffolds are subjected to mechanical stretching to recapitulate the strains occurring in native tendon tissue. Stem cell differentiation is promoted by addition of bone morphogenetic protein 12 (BMP-12) in the culture medium. The aligned orientation of the fibers combined with mechanical stimulation results in highly preferential longitudinal cell orientation and demonstrates enhanced collagen type I and III expression. Additionally, the combination of biochemical and mechanical stimulations promotes the expression of specific tenogenic markers, signatures of efficient cell differentiation towards tendon. The obtained results suggest that the proposed 3D cell-laden aligned system can be used for engineering of scaffolds for tendon regeneration., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: The aim of this study was to analyse the clinical characteristics and outcome of children diagnosed with Ph+ ALL., Material and Methods: A total of 2591 newly diagnosed ALL children were treated in Poland between the years 2005 and 2017. Of those, 44 were diagnosed with Ph(+) ALL. The patients were treated according to protocols: ALL IC-BFM 2002 and 2009 (26 patients), EsPhALL (12 patients), initially ALL IC-BFM and then EsPhALL (6 patients)., Results: The median of follow-up in the observed group was 3 years. Overall survival (OS) and event-free survival (EFS) of Ph+ ALL group were 0.73 and 0.64. OS and EFS of patients after HSCT were 0.78 and 0.66, while without HSCT were 0.6 and 0.6, P = 0.27 and 0.63. OS was 0.8 for patients treated with chemotherapy plus imatinib and 0.61 for chemotherapy alone, P = 0.22, while EFS was 0.66 (imatinib therapy) and 0. 61 (without imatinib), P = 0.41., Conclusion: Our study suggests that adding imatinib to intensive chemotherapy seems to improve outcome. However, this study was limited by a small number of patients and a variety of chemotherapy regimens with or without imatinib., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Chronic myeloid leukemia (CML) constitutes only 2-3% of all leukemias in pediatric patients. Philapelphia chromosome and BCR-ABL fusion are genetic hallmarks of CML, and their presence is crucial for targeted molecular therapy with tyrosine kinase inhibitors (TKIs), which replaced hematopoietic stem cell transplantation (HSCT) as a standard first-line therapy. The disease in pediatric population is rare, and despite molecular and clinical similarities to CML in adults, different approach is needed, due to the long lifetime expectancy and distinct developmental characteristics of affected children., Objectives: The objective of this study is to evaluate treatment with imatinib in Polish pediatric patients with CML., Material and Methods: We analyzed the results of treatment with imatinib in 57 pediatric patients (June 2006 - January 2016) from 14 Polish pediatric hematology and oncology centers., Results: In the study group, 40 patients continued imatinib (median follow-up: 23.4 months), while in 17 the treatment was terminated (median follow-up: 15.1 months) due to therapy failure. In the latter group, 13 patients underwent HSCT, while 4 switched to second-generation TKIs. The 5-year overall survival rate (OS) in the study group was 96%, and the 5-year event-free survival (EFS) was 81%., Conclusions: Our results confirm that the introduction of TKI therapy has revolutionized the treatment of CML in the pediatric population by replacing the previous method of treatment with HSCT and allowing a high percentage of OS and EFS.

Small RNA are very important post-transcriptional regulators in both, bacteria and eukaryotes. One of such sRNA is GraL, encoded in the greA leader region and conserved among enteric bacteria. Here, we conducted a bioinformatics search for GraL's targets in trans and validated our findings in vivo by constructing fusions of probable targets with lacZ and measuring their activity when GraL was overexpressed. Only one target's activity (nudE) decreased under those conditions and was thus selected for further analysis. In the absence of GraL and greA, the nudE::lacZ fusion's β-galactosidase activity was increased. However, a similar effect was also visible in the strain deleted only for greA. Furthermore, overproduction of GreA alone increased the nudE::lacZ fusion's activity as well. This suggests existence of complex regulatory loop-like interactions between GreA, GraL and nudE mRNA. To further dissect this relationship, we performed in vitro EMSA experiments employing GraL and nudE mRNA. However, stable GraL-nudE complexes were not detected, even though the detectable amount of unbound GraL decreased as increasing amounts of nudE mRNA were added. Interestingly, GraL is being bound by Hfq, but nudE easily displaces it. We also conducted a search for genes that are synthetic lethal when deleted along with GraL. This revealed 40 genes that are rendered essential by GraL deletion, however, they are involved in many different cellular processes and no clear correlation was found. The obtained data suggest that GraL's mechanism of action is non-canonical, unique and requires further research.

Children with Down syndrome (DS) have a 20-fold increased risk of developing leukemia compared with the general population. The aim of the study was to analyze the outcome of patients diagnosed with Down syndrome and acute lymphoblastic leukemia (ALL) in Poland between the years 2003 and 2010. A total of 1848 children were diagnosed with ALL (810 females and 1038 males). Of those, 41 (2.2%) had DS. The children were classified into three risk groups: a standard-risk group-14 patients, an intermediate-risk group-24, a high-risk group-3. All patients were treated according to ALLIC 2002 protocol. The median observation time of all patients was 6.1 years, and in patients with DS 5.3 years. Five-year overall survival (OS) was the same in all patients (86% vs 86%, long-rank test, p = .9). The relapse-free survival (RFS) was calculated as 73% in patients with DS and 81% in patients without DS during a median observation time (long-rank test, p = .3). No statistically significant differences were found in the incidence of nonrelapse mortality between those two groups of patients (p = .72). The study was based on children with ALL and Down syndrome who were treated with an identical therapy schedule as ALL patients without DS, according to risk group. This fact can increase the value of the presented results.

Pulsed electromagnetic field (PEMF) influenced the viability of proliferating in vitro peripheral blood mononuclear cells (PBMCs) isolated from Crohn's disease patients as well as acute myeloblastic leukemia (AML) patients by induction of cell death, but did not cause any vital changes in cells from healthy donors. Experiments with lymphoid U937 and monocytic MonoMac6 cell lines have shown a protective effect of PEMF on the death process in cells treated with death inducers. The aim of the current study was to investigate the influence of PEMF on native proliferating leukocytes originating from newly diagnosed acute lymphoblastic leukemia (ALL) patients. The effects of exposure to PEMF were studied in PBMCs from 20 children with ALL. PBMCs were stimulated with three doses of PEMF (7 Hz, 30 mT) for 4 h each with 24 h intervals. After the last stimulation, the cells were double stained with annexin V and propidium iodide dye to estimate viability by flow cytometric analysis. The results indicated an increase of annexin V positive as well as double stained annexin V and propidium iodide positive cells after exposure to threefold PEMF stimulation. A low-frequency pulsed electromagnetic field induces cell death in native proliferating cells isolated from ALL patients. The increased vulnerability of proliferating PBMCs to PEMF-induced interactions may be potentially applied in the therapy of ALL. The analysis of expression of apoptosis-related genes revealed changes in mRNA of some genes engaged in the intrinsic apoptotic pathway belonging to the Bcl-2 family and the pathway with apoptosis-inducing factor (AIF) abundance upon PEMF stimulation of PBMCs.

Introduction: The available legal regulations in Poland do not define the concentration thresholds enabling to differentiate between the states of "after-use" versus "under the influence" of a drug, as it is in the case of alcohol. The aim of the study was to analyse jurisdiction in cases regarding the evaluation of the effects of intoxicating agents and ethanol-like intoxicants and to identify ambiguities and gaps in the applicable regulations leading to problems in preparing expert opinions., Material and Methods: The material included the opinions of experts in the field of toxicology and forensic medicine made by the Department of Forensic Medicine in Lublin in the years 2009-2011 and records obtained in the process of inquiry from the regional prosecutor's offices and courts in 52 cases., Results: Amongst 52 cases in which the ordered toxicology examinations demonstrated the presence of intoxicating agents in drivers' blood (tetrahydrocannabinols in 39 and amphetamine in 21 cases) in 2 cases petty offence proceedings were instituted (Art. 87 of the Petty Offence Code) although high concentrations of xenobiotics indicated the state of being "under the influence" of a narcotic drug (Art. 178a of the Penal Code). Three cases were discontinued despite expert opinions that the drivers were at least in the after-narcotic use state. In only 3 cases were witnesses asked to provide testimony about the circumstances of the driver's conduct., Conclusions: The analysis has demonstrated that judicial bodies expect forensic expertise based exclusively on toxicological examination results; when expert findings are inconclusive, they only administer litigations opportunistically applying the principle of the presumption of innocence understood literally. Considering the above, threshold values of "use" and "influence" of the most commonly detected drugs should be urgently determined.

Background: Adult survivors of childhood malignancy are prone to accelerated atherogenesis and late cardiovascular complications. Plaque formation is initiated by recruitment of monocytes and T-cells into the intima, mediated by adhesion molecules and chemokines expressed by activated endothelial cells., Aim: To assess markers of inflammatory activity, endothelial activation as well as monocyte heterogeneity in adult survivors of childhood acute lymphoblastic leukemia (ALL) who had been treated with chemotherapy without cranial irradiation., Methods and Results: We studied 27 (age: 18-28 years) healthy survivors of childhood ALL and 20 controls (age: 20-31 years). Flow cytometry was used to identify monocyte subsets: classical CD14(++)CD16(-), intermediate CD14(++)CD16(+) and nonclassical CD14(+)CD16(++) monocytes which were further characterized by their expression of HLA-DR and β2-integrins CD11b/CD18 and CD11c/CD18. In ALL survivors we found increased levels of pentraxin-3 (median [interquartile range]: 0.63 [0.36-0.94] vs. 0.40 [0.32-0.57] ng/ml; p = 0.03), soluble vascular cell adhesion molecule-1 (687 [597-761] vs. 558 [534-702]ng/ml; p = 0.02), osteoprotegerin (mean ± SD: 5.24 ± 1.00 vs. 4.42 ± 1.34 pmol/l; p = 0.02) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (107.0 ± 23.6 vs. 89.5 ± 18.9 pg/ml; p = 0.01), whereas C-reactive protein, interleukin 6 and 18, TNF-α, monocyte chemotactic protein-1 and soluble intercellular adhesion molecule-1 were unchanged. Former ALL patients exhibited elevated counts of intermediate monocytes (6.3 ± 4.0 vs. 4.3 ± 1.5% of blood monocytes; p = 0.03). CD11b/CD18 and CD11c/CD18 expression on intermediate monocytes tended to be higher in ALL survivors (1917 ± 993 vs. 1396 ± 673 MFI [median fluorescence intensity]; p = 0.06 and 3883 ± 1445 vs. 3185 ± 645 MFI; p = 0.05, respectively)., Conclusion: Our findings suggest chronic inflammatory activation and immune dysregulation in adult survivors of childhood ALL, which can translate into late cardiovascular morbidity., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Background: Adult survivors of childhood malignancy are predisposed to late cardiovascular (CV) complications. Our aim was to estimate plasma levels of the endogenous nitric oxide formation inhibitor asymmetric dimethylarginine (ADMA), in long-term survivors of childhood acute lymphoblastic leukemia (ALL) treated with only chemotherapy., Methods: ADMA and its isomer symmetric dimethylarginine (SDMA) were measured in 25 former ALL patients (aged 18-28 years) who had survived without recurrent disease ≥ 5 years from completing chemotherapy without cranial irradiation, and in 20 healthy controls (aged 20-31 years)., Results: Characteristics of the both groups were similar, except for lower high-density lipoproteins-cholesterol (HDL-C) in ALL survivors. Compared to controls, the former ALL patients exhibited significant, albeit small, rises in levels of ADMA (0.63 ± 0.09 [SD] vs. 0.57 ± 0.07 μmol/L; p=0.016), but not SDMA, with a consequently increased ADMA to SDMA ratio (1.08 ± 0.22 vs. 0.91 ± 0.16; p=0.004). The effect of former ALL on ADMA was attenuated (intergroup p=0.10 [ANCOVA]) upon adjustment for HDL-C (ADMA vs. HDL-C regression coefficient: -0.065 ± 0.030 [SEM]; p=0.03)., Conclusions: ADMA is elevated in adult childhood ALL survivors, which can reflect late detrimental chemotherapy effects, partially related to minor lipid profile changes. Whether these subtle ADMA elevations might herald future CV morbidity, remains to be elucidated.