An estrone-salicylaldehyde thiosemicarbazone hybrid (
estrone-TSC
) containing integrated domains was designed and synthesized with excellent yield
via
the condensation reaction of thiosemicarbazide ...and 2-formyl-estrone under optimized microwave reaction conditions. A structurally related bicyclic derivative (
thn-TSC
) starting from 5,6,7,8-tetrahydro-1-naphtol (
th-1-n
) was also prepared in addition to their copper(
ii
) complexes. The ligands have somewhat higher p
K
a
values determined for the deprotonation of the hydroxyl group by UV-visible spectrophotometric and fluorometric titrations than the reference compound salicylaldehyde thiosemicarbazone (
STSC
), and are neutral at physiological pH. The novel conjugates are more lipophilic and possess higher membrane permeability than
STSC
based on the
n
-octanol/water partitioning and the parallel artificial membrane permeability assays, respectively. The isolated Cu(estrone-TSCH
−2
) and Cu(thn-TSCH
−2
) complexes were characterized by ESI-MS, UV-visible and EPR spectroscopy and a detailed solution study was performed to reveal their stoichiometry, stability and reduction by glutathione. The crystal structure of the ligand
thn-TSC
and its complex Cu(thn-TSCH
−1
)Cl was studied by single crystal X-ray diffraction method. The complexes are fairly stable at pH 7.4, the observed stability order is
STSC
<
thn-TSC
<
estrone-TSC
, and are able to oxidize glutathione readily. The novel ligands
thn-TSC
and
estrone-TSC
were found to be only moderately cytotoxic against several human cancer cell lines; however rather low IC
50
values were measured in the hormone-responsive MCF-7 breast cancer cell lines (
thn-TSC
: 3.7 μM,
estrone-TSC
: 6.4 μM). The copper(
ii
) complexes exhibited high cytotoxicity (IC
50
< 0.3-2 μM) and were considerably more cytotoxic than the respective ligands. Low level of reactive oxygen species was measured and a weak GSH depletion was observed for the complexes of
thn-TSC
and
estrone-TSC
in SUM159 breast cancer cells, thus their mechanism of action might be related to the induction of oxidative stress.
Copper complex of a novel estrone-thiosemicarbazone hybrid with significant cytotoxicity, lipophilicity and solution stability in addition to its structurally related bicyclic analogue.
In this project, we used formalin‐fixed paraffin‐embedded (FFPE) tissue samples to measure thousands of spectra per tissue core with Fourier transform mid‐infrared spectroscopy using an FT‐IR imaging ...system. These cores varied between normal colon (NC) and colorectal primer carcinoma (CRC) tissues. We created a database to manage all the multivariate data obtained from the measurements. Then, we applied classifier algorithms to identify the tissue based on its yielded spectra. For classification, we used the random forest, a support vector machine, XGBoost, and linear discriminant analysis methods, as well as three deep neural networks. We compared two data manipulation techniques using these models and then applied filtering. In the end, we compared model performances via the sum of ranking differences (SRD).
Thousands of MIR spectra were measured from formalin‐fixed paraffin‐embedded tissue samples that varied between normal colon and colorectal primer carcinoma tissues. Machine learning algorithms, including deep neural networks, were applied to predict the type of tissue a spectrum belonged to. Further analysis was conducted with data manipulation techniques and the sum of ranking differences (SRD).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The solution chemical properties such as proton dissociation, complex formation with copper(II) and gallium(III) ions in addition to antibacterial and antitumor activity of a novel tridentate ...salicyaldehyde semicarbazone-estrone hybrid (estrone-SC) and a related bicyclic compound (thn-SC) were investigated. The crystal structure of complex Cu(thn-SCH−1)Cl was studied by single crystal X-ray diffraction method. Estrone-SC and thn-SC form mono-ligand complexes with Cu(II) characterized by relatively high stability, however, they are much less stable than their thiosemicarbazone analogues. The neutral Cu(II) complexes with (O−,N,O−)(H2O) coordination mode predominate at physiological pH. Estrone-SC and thn-SC are more efficient Ga(III) binders in comparison with thiosemicarbazones, although the complexes also suffer dissociation at pH 7.4. The Cu(II) complex of estrone-SC displayed significant cytotoxicity in A549, SW480 and CH1/PA cancer cells, and moderate apoptosis induction and ROS formation. The semicarbazone compounds did not exhibit antibacterial effect; unlike the related Cu(II)-thiosemicarbazone complexes represented by the fairly low MIC values (3–50 μM) obtained on the Gram-positive Staphylococcus aureus and Enterococcus faecalis bacteria.
A salicylaldehyde semicarbazone-estrone hybrid and its complexation with Cu(II) and Ga(III) was studied. The exchange of S to O in the thiocarbamoyl moiety results in significant effect on pKa, complex stability, antitumor and antibacterial activity. Display omitted
•A novel tridentate salicyaldehyde semicarbazone-estrone hybrid.•Significantly higher stability complexes formed with Cu(II) than with Ga(III).•Estrone hybridization results in the higher solution stability of the complexes.•Cytotoxicity of the semicarbazone-estrone hybrid is enhanced upon Cu(II) complexation.•Exchange of S to O in the thiocarbamoyl moiety strongly influences the bioactivities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aim of this study was to investigate the effects of caffeine on reaction time during a specific taekwondo task and athletic performance during a simulated taekwondo contest. Ten taekwondo ...athletes ingested either 5 mg·kg⁻¹ body mass caffeine or placebo and performed two combats (spaced apart by 20 min). The reaction-time test (five kicks "Bandal Tchagui") was performed immediately prior to the first combat and immediately after the first and second combats. Caffeine improved reaction time (from 0.42 ± 0.05 to 0.37 ± 0.07 s) only prior to the first combat (P = 0.004). During the first combat, break times during the first two rounds were shorter in caffeine ingestion, followed by higher plasma lactate concentrations compared with placebo (P = 0.029 and 0.014, respectively). During the second combat, skipping-time was reduced, and relative attack times and attack/skipping ratio was increased following ingestion of caffeine during the first two rounds (all P < 0.05). Caffeine resulted in no change in combat intensity parameters between the first and second combat (all P > 0.05), but combat intensity was decreased following placebo (all P < 0.05). In conclusion, caffeine reduced reaction time in non-fatigued conditions and delayed fatigue during successive taekwondo combats.
After several years of development and continuous improvement of the BIPM Kibble balance, mass measurement of a 1 kg Pt/Ir artefact in terms of the Planck constant has been carried out. The paper ...describes the apparatus and its alignment, and explains the measurement and data processing. The balance operates in a one-mode and two measurement phase scheme using a bifilar coil. The mass value of the artefact was measured in vacuum with a relative standard uncertainty of 49 µg. This value differs from the value deduced from the calibration following the dissemination process after the redefinition of the kilogram by 15 µg.
Objective
Distress screening programs aim to ensure appropriate psychooncological support for cancer patients, but many eligible patients do not use these services. To improve distress management, we ...need to better understand patients' supportive care needs. In this paper, we report the first key finding from a longitudinal study that focused on patients' intentions to use psychooncological support and its association with distress and uptake of the psychooncology service.
Methods
We conducted a prospective, observational study in an Oncology Outpatient Clinic and assessed distress, intention to use psychooncological support, and uptake of the psychooncology service by using the Distress Thermometer, a semistructured interview, and hospital records. We analyzed data with a mixed‐methods approach.
Results
Of 333 patients (mean age 61 years; 55% male; 54% Distress Thermometer ≥ 5), 25% intended to use the psychooncology service (yes), 33% were ambivalent (maybe), and 42% reported no intention (no). Overall, 23% had attended the psychooncology service 4 months later. Ambivalent patients reported higher distress than patients with no intention (odds ratio = 1.18, 95% confidence interval 1.06‐1.32) but showed significantly lower uptake behavior than patients with an intention (odds ratio = 14.04, 95% confidence interval 6.74‐29.24). Qualitative analyses revealed that ambivalent patients (maybe) emphasized fears and uncertainties, while patients with clear intentions (yes/no) emphasized knowledge, attitudes, and coping concepts.
Conclusions
We identified a vulnerable group of ambivalent patients with high distress levels and low uptake behavior. To optimize distress screening programs, we suggest addressing and discussing patients' supportive care needs in routine clinical practice.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The Kibble balance is expected to become an important instrument in the near future for realizing the unit of mass, the kilogram, in the revised international system of units (SI). The Kibble balance ...assumes an equality of two magnetic profiles measured in the weighing and velocity phases. A recent study conducted in the Kibble balance group at the Bureau International des Poids et Mesures (BIPM) showed that the coil current could significantly affect the magnetic profile, which should be carefully taken into account in the Kibble balance experiment. This paper gives a deeper understanding and investigation of the effect, and discusses the magnetic profile change due to the coil current, for both the classical two-mode and the one-mode Kibble balances. The coil current effect has been theoretically and experimentally investigated based on a typical magnet design with an air gap. One important conclusion found in the one-mode Kibble balance is that the magnetic profile change measured in the velocity phase is twice the change in the weighing phase. A compensation suggestion, to minimize the profile change due to the coil current in a BIPM-type magnet, is presented.
Abstract Introduction Recently extracellular vesicles (exosomes, microparticles also referred to as microvesicles and apoptotic bodies) have attracted substantial interest as potential biomarkers and ...therapeutic vehicles. However, analysis of microparticles in biological fluids is confounded by many factors such as the activation of cells in the blood collection tube that leads to in vitro vesiculation. In this study we aimed at identifying an anticoagulant that prevents in vitro vesiculation in blood plasma samples. Materials and Methods We compared the levels of platelet microparticles and non-platelet-derived microparticles in platelet-free plasma samples of healthy donors. Platelet-free plasma samples were isolated using different anticoagulant tubes, and were analyzed by flow cytometry and Zymuphen assay. The extent of in vitro vesiculation was compared in citrate and acid-citrate-dextrose (ACD) tubes. Results Agitation and storage of blood samples at 37 °C for 1 hour induced a strong release of both platelet microparticles and non-platelet-derived microparticles. Strikingly, in vitro vesiculation related to blood sample handling and storage was prevented in samples in ACD tubes. Importantly, microparticle levels elevated in vivo remained detectable in ACD tubes. Conclusions We propose the general use of the ACD tube instead of other conventional anticoagulant tubes for the assessment of plasma microparticles since it gives a more realistic picture of the in vivo levels of circulating microparticles and does not interfere with downstream protein or RNA analyses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective To evaluate the effectiveness of telephone based peer support in the prevention of postnatal depression.Design Multisite randomised controlled trial.Setting Seven health regions across ...Ontario, Canada.Participants 701 women in the first two weeks postpartum identified as high risk for postnatal depression with the Edinburgh postnatal depression scale and randomised with an internet based randomisation service.Intervention Proactive individualised telephone based peer (mother to mother) support, initiated within 48-72 hours of randomisation, provided by a volunteer recruited from the community who had previously experienced and recovered from self reported postnatal depression and attended a four hour training session.Main outcome measures Edinburgh postnatal depression scale, structured clinical interview-depression, state-trait anxiety inventory, UCLA loneliness scale, and use of health services.Results After web based screening of 21 470 women, 701 (72%) eligible mothers were recruited. A blinded research nurse followed up more than 85% by telephone, including 613 at 12 weeks and 600 at 24 weeks postpartum. At 12 weeks, 14% (40/297) of women in the intervention group and 25% (78/315) in the control group had an Edinburgh postnatal depression scale score >12 (χ2=12.5, P<0.001; number need to treat 8.8, 95% confidence interval 5.9 to 19.6; relative risk reduction 0.46, 95% confidence interval 0.24 to 0.62). There was a positive trend in favour of the intervention group for maternal anxiety but not loneliness or use of health services. For ethical reasons, participants identified with clinical depression at 12 weeks were referred for treatment, resulting in no differences between groups at 24 weeks. Of the 221 women in the intervention group who received and evaluated their experience of peer support, over 80% were satisfied and would recommend this support to a friend.Conclusion Telephone based peer support can be effective in preventing postnatal depression among women at high risk.Trial registration ISRCTN 68337727.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The objective of the present study was to verify if active recovery (AR) applied after a judo match resulted in a better performance when compared to passive recovery (PR) in three tasks varying in ...specificity to the judo and in measurement of work performed: four upper-body Wingate tests (WT); special judo fitness test (SJFT); another match. For this purpose, three studies were conducted. Sixteen highly trained judo athletes took part in study 1, 9 in study 2, and 12 in study 3. During AR judokas ran (15 min) at the velocity corresponding to 70% of 4 mmol l
−1
blood lactate intensity (~50%
peak), while during PR they stayed seated at the competition area. The results indicated that the minimal recovery time reported in judo competitions (15 min) is long enough for sufficient recovery of WT performance and in a specific high-intensity test (SJFT). However, the odds ratio of winning a match increased ten times when a judoka performed AR and his opponent performed PR, but the cause of this phenomenon cannot be explained by changes in number of actions performed or by changes in match’s time structure.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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