Methotrexate-associated oral mucositis in children with acute lymphoblastic leukemia

Methotrexate is an antifolate widely used in oncology and rheumatology that plays an important role in the treatment of acute lymphoblastic leukemia in children. One of its most common side effects is oral mucositis, which is a general term for ulceration and inflammation of the mucous membrane of the mouth. It can severely affect a patient’s quality of life, causes poor nutrition, and may lead to discontinuation of the next course of chemotherapy. Oral mucositis typically develops a few days after chemotherapy infusion. Due to this risk, it appears reasonable to use preventive agents against oral mucositis before the inclusion of methotrexate in therapy. To date, clinical trials have examined the effectiveness of medications such as glutamine, palifermin, chlorhexidine, amifostine, cyclooxygenase-1 inhibitor, leucovorin or other methods including laser therapy and oral cryotherapy. There are also several methods used to control already established inflammation and reduce pain more effectively: laser therapy, platelet-rich plasma and platelet gel, taxifolin, film-forming and coating agents. A crucial role is played by supportive interventions involving analgesic treatment, including topical morphine and benzydamine and a modern approach to pain management – for example, the use of virtual reality

Association of germline genetic variants in RFC, IL15 and VDR genes with minimal residual disease in pediatric B-cell precursor ALL

Minimal residual disease (MRD) enables reliable assessment of risk in acute lymphoblastic leukemia (ALL). However, little is known on association between MRD status and germline genetic variation. We examined 159 Caucasian (Slavic) patients with pediatric ALL, treated according to ALL-IC-BFM 2002/2009 protocols, in search for association between 23 germline polymorphisms and MRD status at day 15, day 33 and week 12, with adjustment for MRD-associated clinical covariates. Three variants were significantly associated with MRD: rs1544410 in VDR (MRD-day15); rs1051266 in RFC (MRD-day33, MRD-week12), independently and in an additive effect with rs10519613 in IL15 (MRD-day33). The risk alleles for MRD-positivity were: A allele of VDR (OR = 2.37, 95%CI = 1.07–5.21, P = 0.03, MRD-day15); A of RFC (OR = 1.93, 95%CI = 1.05–3.52, P = 0.03, MRD-day33 and MRD-week12, P < 0.01); A of IL15 (OR = 2.30, 95%CI = 1.02–5.18, P = 0.04, MRD-day33). The risk for MRD-day33-positive status was higher in patients with risk alleles in both RFC and IL15 loci than in patients with risk alleles in one locus or no risk alleles: 2 vs. 1 (OR = 3.94, 95% CI = 1.28–12.11, P = 0.024), 2 vs. 0 (OR = 6.75, 95% CI = 1.61–28.39, P = 0.012). Germline variation in genes related to pharmacokinetics/pharmacodynamics of anti-leukemic drugs and to anti-tumor immunity of the host is associated with MRD status and might help improve risk assessment in ALL

Modelling of combined ICRF and NBI heating in JET hybrid plasmas

During the 2015-2016 JET campaigns many efforts have been devoted to the exploration of high performance plasma scenarios envisaged for ITER operation. In this paper we model the combined ICRF+NBI heating in selected key hybrid discharges using PION. The antenna frequency was tuned to match the cyclotron frequency of minority hydrogen (H) at the center of the tokamak coinciding with the second harmonic cyclotron resonance of deuterium. The modelling takes into account the synergy between ICRF and NBI heating through the second harmonic cyclotron resonance of deuterium beam ions which allows us to assess its impact on the neutron rate RNT. We evaluate the influence of H concentration which was varied in different discharges in order to test their role in the heating performance. According to our modelling, the ICRF enhancement of RNT increases by decreasing the H concentration which increases the ICRF power absorbed by deuterons. We find that in the recent hybrid discharges this ICRF enhancement was in the range of 10-25%. Finally, we extrapolate the results to D-T and find that the best performing hybrid discharges correspond to an equivalent fusion power of ∼7.0 MW in D-T.This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014-2018 under grant agreement No 633053. The views and opinions expressed herein do not necessarily reflect those of the European Commission. Dani Gallart would like to thank “La Caixa” for support of his PhD studies.Peer ReviewedPostprint (published version

Moderate exercise may attenuate some aspects of immunosenescence

BACKGROUND: Immunosenescence is related to the deterioration of many immune functions, which may be manifested in increased susceptibility to infection, cancer, and autoimmunity. Lifestyle factors, such as diet or physical activity, may influence the senescence of the immune system. It is widely accepted that moderate physical activity may cause beneficial effects for physical and psychological health as well as for the immune system activity in aged people. METHODS: Thirty elderly women aged 62 to 86 were subjected to a two-years authorized physical activity program. Peripheral blood lymphocytes distribution and the production of cytokines involved in the immune response development and regulation (IL-2, IL-4 and IFN-γ) were investigated. The same parameters were evaluated in two control groups of women: a sedentary group of 12 elderly women selected for the second round of the physical activity program and in a group of 20 sedentary young women. Flow cytometry methods were used for the examination of surface markers on peripheral blood lymphocytes and intracellular cytokines expression. RESULTS: The distribution of the main lymphocytes subpopulations in the peripheral blood of elderly women did not show changes after long-term moderate physical training. The percentage of lymphocytes expressing intracellular IL-2 was higher in the group of women attending 2-years physical activity program than in the control group of elderly sedentary women, and it was similar to the value estimated in the group of young sedentary women. There was no difference in the intracellular expression of IL-4 and IFN-γ between the active and elderly sedentary women. CONCLUSIONS: Our results suggest that moderate, long-term physical activity in elderly women may increase the production of IL-2, an important regulator of the immune response. This may help ameliorate immunosenescence in these women

Mechanical thrombectomy in acute stroke – Five years of experience in Poland

Objectives Mechanical thrombectomy (MT) is not reimbursed by the Polish public health system. We present a description of 5 years of experience with MT in acute stroke in Comprehensive Stroke Centers (CSCs) in Poland. Methods and results We retrospectively analyzed the results of a structured questionnaire from 23 out of 25 identified CSCs and 22 data sets that include 61 clinical, radiological and outcome measures. Results Most of the CSCs (74%) were founded at University Hospitals and most (65.2%) work round the clock. In 78.3% of them, the working teams are composed of neurologists and neuro-radiologists. All CSCs perform CT and angio-CT before MT. In total 586 patients were subjected to MT and data from 531 of them were analyzed. Mean time laps from stroke onset to groin puncture was 250±99min. 90.3% of the studied patients had MT within 6h from stroke onset; 59.3% of them were treated with IV rt-PA prior to MT; 15.1% had IA rt-PA during MT and 4.7% – emergent stenting of a large vessel. M1 of MCA was occluded in 47.8% of cases. The Solitaire device was used in 53% of cases. Successful recanalization (TICI2b–TICI3) was achieved in 64.6% of cases and 53.4% of patients did not experience hemorrhagic transformation. Clinical improvement on discharge was noticed in 53.7% of cases, futile recanalization – in 30.7%, mRS of 0–2 – in 31.4% and mRS of 6 in 22% of cases. Conclusion Our results can help harmonize standards for MT in Poland according to international guidelines

Wpływ dodatków biowęglowych na właściwości funkcjonalne smarów plastycznych

The article presents the results of tests on tribological and physicochemical properties of plastic greases, in which the dispersing phase was highly refined mineral oil and the dispersed phase (thickener) lithium stearate. The functional additives were biocarbon, which were obtained in the pyrolysis process of waste of natural origin, i.e. stems with corn leaves, wheat straw, flax straw, and cherry stones. The compositions containing 5% m/m biocarbon were prepared. Their evaluated on the functional properties of plastic greases was assessed. Tribological characteristics of the greases compositions were determined using the T-02 tester in accordance with the requirements of the subject standards. The effect of biocarbon used on anti-wear (Goz) and anti-seizing (Pt, poz) plastic greases was determined. An assessment was also made of the effect of plant biocarbon on changes in basic physicochemical properties of the composition of plastic greases, i.e. penetration, dropping temperature, and thermo-oxidative stability. It was found that some of the biocarbon significantly improve the tribological properties of plastic greases without significantly affecting the change of key physicochemical parameters. The most beneficial impact of the tested additives on the operational properties of plastic greases was observed when using biocarbon from wheat straw. In some cases, a lower oxidative resistance of biocarbon grease is observed compared to grease without the addition of biocarbon.W artykule przedstawiono wyniki badań właściwości tribologicznych i fizykochemicznych smarów plastycznych, w których fazą dyspergującą był wysokorafinowany olej mineralny, a fazą zdyspergowaną (zagęszczaczem) stearynian litu, dodatkami funkcyjnymi były biowęgle otrzymane w procesie pirolizy odpadów pochodzenia naturalnego tj. łodyg wraz z liśćmi kukurydzy, słomy pszenicznej, paździerzy lnianych i pestek wiśni. Sporządzono kompozycje zawierające 5% m/m biowęgli i oceniono ich wpływ na właściwości funkcjonalne otrzymanych smarów plastycznych. Charakterystyki tribologiczne kompozycji smarowych wyznaczono z wykorzystaniem testera T-02 zgodnie z wymaganiami norm przedmiotowych. Określono wpływ zastosowanych biowęgli na właściwości przeciwzużyciowe (Goz) i przeciwzatarciowe (Pt, poz) opracowanych smarów plastycznych. Dokonano także oceny wpływu biowęgli pochodzenia roślinnego na zmiany podstawowych właściwości fizykochemicznych kompozycji smarów plastycznych, tj. penentrację, temperaturę kroplenia i stabilność termooksydacyjną. Stwierdzono, że niektóre z biowęgli zdecydowanie poprawiają właściwości tribologiczne smarów plastycznych, nie wpływając istotnie na zmianę kluczowych parametrów fizykochemicznych. Najkorzystniejszy wpływ badanych dodatków na właściwości eksploatacyjne smarów plastycznych zaobserwowano w przypadku zastosowania biowegli ze słomy pszenicznej. W niektórych przypadkach obserwuje się niższą odporność oksydacyjną smarów biowęglowych w porównaniu ze smarem bez dodatku biowęgla

Methotrexate-associated oral mucositis in children with acute lymphoblastic leukemia

Methotrexate is an antifolate widely used in oncology and rheumatology that plays an important role in the treatment of acute lymphoblastic leukemia in children. One of its most common side effects is oral mucositis, which is a general term for ulceration and inflammation of the mucous membrane of the mouth. It can severely affect a patient’s quality of life, causes poor nutrition, and may lead to discontinuation of the next course of chemotherapy. Oral mucositis typically develops a few days after chemotherapy infusion. Due to this risk, it appears reasonable to use preventive agents against oral mucositis before the inclusion of methotrexate in therapy. To date, clinical trials have examined the effectiveness of medications such as glutamine, palifermin, chlorhexidine, amifostine, cyclooxygenase-1 inhibitor, leucovorin or other methods including laser therapy and oral cryotherapy. There are also several methods used to control already established inflammation and reduce pain more effectively: laser therapy, platelet-rich plasma and platelet gel, taxifolin, film-forming and coating agents. A crucial role is played by supportive interventions involving analgesic treatment, including topical morphine and benzydamine and a modern approach to pain management – for example, the use of virtual reality