1,612 research outputs found
Baseline and recurrent exposure to the standard dose of artemisinin-based combination therapies (ACTs) induces oxidative stress and liver damage in mice (BALB/c)
Background In malaria-endemic countries, repeated intake of artemisinin-based combination therapies (ACTs)
is rampant and driven by drug resistance, improper usage, and easy accessibility. Stress effects and potential liver tox-
icity due to the frequent therapeutic use of ACTs have not been extensively studied. Here, we investigated the effects
of repeated treatment with standard doses of the commonly used ACTs artemether/lumefantrine (A/L) and artesu-
nate-amodiaquine (A/A) on oxidative stress and liver function markers in male mice (BALB/c).
Methods Forty Five mice were divided into three groups: control, A/L, and A/A. The drugs were administered three
days in a row per week, and the regimen was repeated every two weeks for a total of six cycles. The levels of oxidative
stress and liver function markers were measured in both plasma and liver tissue after initial (baseline) and repeated
exposures for the second, third, and sixth cycles.
Results Exposure to A/L or A/A caused a significant (p < 0.001) increase in plasma malondialdehyde (MDA) lev-
els after the first and repeated exposure periods. However, Hepatic MDA levels increased significantly (p < 0.01)
only after the sixth exposure to A/A. Following either single or repeated exposure to A/L or A/A, plasma and liver
glutathione peroxidase (GPx) and catalase (CAT) activities, plasma aspartate and alanine transaminase, alkaline phos-
phatase activity, and bilirubin levels increased, whereas total plasma protein levels decreased significantly (p < 0.001).
Varying degrees of hepatocyte degeneration and blood vessel congestion were observed in liver tissues after a single
or repeated treatment period.
Conclusion Irrespective of single or repeated exposure to therapeutic doses of A/L or A/A, plasma oxidative stress
and liver damage were observed. However, long-term repeated A/A exposure can led to hepatic stress. Compensa-
tory processes involving GPx and CAT activities may help reduce the observed stress
Thermodynamic properties of ZnO with in mie-gruneisen hypothesis
Zink oxide (mineral name: Zincite) is an attractive wide band gap semiconductor due to its large number of industrial applications such as in the production of solar cells,
liquid-crystal displays, electrochromic devices, LED, as well as adhesive taps, automobile tires, ceramics, glass, varistors, etc. It is due to versatile nature of ZnO, in we have studied its thermal properties at high temperatures. Theoretically, complete ab initio investigations at elevated temperatures are restricted due largely to computational complexity of many-body nature. We have therefore used an consistent iterative scheme to include thermal effect by combining the universal equation of
state (UEOS) to the Mie-Gruneisen hypothesis. It is demonstrated that from the knowledge of cohesive properties at ambient condition various thermodynamic properties can be predicted at finite temperatures and pressures. For example, presently calculated relative volume-thermal expansions, static EOS are in good accordance with experimental results.
When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/2787
Integrated safety analysis: Frequency of urinary tract infections in patients with psoriasis treated with ixekizumab.
Horseplay, care and hands on hard work: gendered strategies of a project manager on a construction site
The discourse of managerial expertise favours rational analysis and masculine ideals but contemporary management literature also recognises the value of well-being and employee voice in the workplace. Drawing upon narrative analysis of interview data, we share unique insights into the lived experiences of Laura, one female project manager who recently managed a construction site in the Midlands in the UK. In contrast to previous research which indicates that female managers tend to conform to quite a traditional set of gender behaviours, Laura embraces a range of workplace appropriate gendered strategies, such as hard work and horseplay, together with sensitivity and caring. She draws from this mix of gendered strategies in negotiating between two different discourses of construction; one professional and one tough and practical. Her behaviour both reproduces the masculine ideals (through horseplay and heroic management) and opens up possibilities for modernising construction management (by caring). It is this combination of strategies that is at the heart of tacit expertise for Laura. Theoretically, the discussion adds to the development of a more nuanced understanding of management expertise as situated and person specific knowledge that draws on both the explicit and tacit. Specifically, the centrality of gendered strategies beyond the masculine ideals to success on site is highlighted
Comprehensive molecular characterization of urachal adenocarcinoma reveals commonalities with colorectal cancer, including a hypermutable phenotype
Purpose Urachal adenocarcinoma is a rare type of primary bladder adenocarcinoma that comprises less than 1% of all bladder cancers. The low incidence of urachal adenocarcinomas does not allow for an evidence-based approach to therapy. Transcriptome profiling of urachal adenocarcinomas has not been previously reported.Wehypothesized that an in-depth molecular understanding of urachal adenocarcinoma would uncover rational therapeutic strategies. Patients and Methods We performed targeted exon sequencing and global transcriptome profiling of 12 urachal tumors to generate a comprehensive molecular portrait of urachal adenocarcinoma. A single patient with an MSH6 mutation was treated with the anti-programmed death-ligand 1 antibody, atezolizumab. Results Urachal adenocarcinoma closely resembles colorectal cancer at the level of RNA expression, which extends previous observations that urachal tumors harbor genomic alterations that are found in colorectal adenocarcinoma. A subset of tumors was found to have alterations in genes that are associated with microsatellite instability (MSH2 and MSH6) and hypermutation (POLE).Apatient with anMSH6mutation was treated withimmunecheckpoint blockade, which resulted in stable disease. Conclusion Because clinical trials are next to impossible for patients with rare tumors, precision oncology may be an important adjunct for treatment decisions. Our findings demonstrate that urachal adenocarcinomas molecularly resemble colorectal adenocarcinomas at the level ofRNA expression, are the first report, to our knowledge, of MSH2andMSH6mutations in this disease, and support the consideration of immune checkpoint blockade as a rational therapeutic treatment of this exceedingly rare tumor
Disease burden and conditioning regimens in ASCT1221, a randomized phase II trial in children with juvenile myelomonocytic leukemia: A Children's Oncology Group study
Background: Most patients with juvenile myelomonocytic leukemia (JMML) are curable only with allogeneic hematopoietic cell transplantation (HCT). However, the current standard conditioning regimen, busulfan-cyclophosphamide-melphalan (Bu-Cy-Mel), may be associated with higher risks of morbidity and mortality. ASCT1221 was designed to test whether the potentially less-toxic myeloablative conditioning regimen containing busulfan-fludarabine (Bu-Flu) would be associated with equivalent outcomes. Procedure: Twenty-seven patients were enrolled on ASCT1221 from 2013 to 2015. Pre- and post-HCT (starting Day +30) mutant allele burden was measured in all and pre-HCT therapy was administered according to physician discretion. Results: Fifteen patients were randomized (six to Bu-Cy-Mel and nine to Bu-Flu) after meeting diagnostic criteria for JMML. Pre-HCT low-dose chemotherapy did not appear to reduce pre-HCT disease burden. Two patients, however, received aggressive chemotherapy pre-HCT and achieved low disease-burden state; both are long-term survivors. All four patients with detectable mutant allele burden at Day +30 post-HCT eventually progressed compared to two of nine patients with unmeasurable allele burden (P = 0.04). The 18-month event-free survival of the entire cohort was 47% (95% CI, 21–69%), and was 83% (95% CI, 27–97%) and 22% (95% CI, 03–51%) for Bu-Cy-Mel and Bu-Flu, respectively (P = 0.04). ASCT1221 was terminated early due to concerns that the Bu-Flu arm had inferior outcomes. Conclusions: The regimen of Bu-Flu is inadequate to provide disease control in patients with JMML who present to HCT with large burdens of disease. Advances in molecular testing may allow better characterization of biologic risk, pre-HCT responses to chemotherapy, and post-HCT management
Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA
An investigation of the hadronic final state in diffractive and
non--diffractive deep--inelastic electron--proton scattering at HERA is
presented, where diffractive data are selected experimentally by demanding a
large gap in pseudo --rapidity around the proton remnant direction. The
transverse energy flow in the hadronic final state is evaluated using a set of
estimators which quantify topological properties. Using available Monte Carlo
QCD calculations, it is demonstrated that the final state in diffractive DIS
exhibits the features expected if the interaction is interpreted as the
scattering of an electron off a current quark with associated effects of
perturbative QCD. A model in which deep--inelastic diffraction is taken to be
the exchange of a pomeron with partonic structure is found to reproduce the
measurements well. Models for deep--inelastic scattering, in which a
sizeable diffractive contribution is present because of non--perturbative
effects in the production of the hadronic final state, reproduce the general
tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil
A Search for Selectrons and Squarks at HERA
Data from electron-proton collisions at a center-of-mass energy of 300 GeV
are used for a search for selectrons and squarks within the framework of the
minimal supersymmetric model. The decays of selectrons and squarks into the
lightest supersymmetric particle lead to final states with an electron and
hadrons accompanied by large missing energy and transverse momentum. No signal
is found and new bounds on the existence of these particles are derived. At 95%
confidence level the excluded region extends to 65 GeV for selectron and squark
masses, and to 40 GeV for the mass of the lightest supersymmetric particle.Comment: 13 pages, latex, 6 Figure
Forward pi^0 Production and Associated Transverse Energy Flow in Deep-Inelastic Scattering at HERA
Deep-inelastic positron-proton interactions at low values of Bjorken-x down
to x \approx 4.10^-5 which give rise to high transverse momentum pi^0 mesons
are studied with the H1 experiment at HERA. The inclusive cross section for
pi^0 mesons produced at small angles with respect to the proton remnant (the
forward region) is presented as a function of the transverse momentum and
energy of the pi^0 and of the four-momentum transfer Q^2 and Bjorken-x.
Measurements are also presented of the transverse energy flow in events
containing a forward pi^0 meson. Hadronic final state calculations based on QCD
models implementing different parton evolution schemes are confronted with the
data.Comment: 27 pages, 8 figures and 3 table
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