Conventional cytogenetics (CC) can be used to identify chromosomal abnormalities that are predictors of treatment outcome in acute lymphoblastic leukemia (ALL). The detection of abnormalities in ALL ...is difficult because low mitotic index and poor-quality metaphases are obtained. Flow cytometry (FC) and fluorescence in situ hybridization (FISH) can be used to detect aneuploidy in any phase of the cell cycle, increasing the number of analyzable cells. The aim of this study was to develop a strategy combining these methods to improve the frequency of chromosome abnormality detection. One hundred children with newly diagnosed ALL were included. CC and DNA content analysis by FC were performed in all patients. The numerical abnormalities identified by both methods were compared and patients were classified as concordant or discordant. FISH was used to support aneuploidy results in discrepant cases using centromeric probes for the chromosomes most frequently involved in aneuploidy. CC and FC showed high concordance (86%). Fourteen cases were discrepant: nine showed hypodiploidy and low hyperdiploidy by cytogenetics and five showed high hyperdiploidy by FC. FISH confirmed aneuploidy in 12 cases in which it could be performed. High hyperdiploidy was the most common abnormality; the 31 cases showing this aneuploidy were identified by FC. The search for abnormalities must begin by measuring DNA content to detect this aneuploidy, which is useful to evaluate the patient's risk. However, it is important to screen for structural abnormalities by CC or molecular techniques. This strategy may detect chromosomal abnormalities, optimizing resources in laboratories where not all the screening methods are available.
Abstract Objective The measurement of dead space to tidal volume fraction (Vd/Vt) using various methodologies has been shown to be a reliable predictor of mortality in critically ill patients. In ...this study, we evaluated the correlation of a validated equation using clinically available information to predict calculation of Vd/Vt with clinically relevant outcome parameters in patients requiring mechanical ventilation. Methods Calculations of Vd/Vt were obtained based upon a previously published prediction equation for dead space ventilation fraction: Vd/Vt = 0.320 + 0.0106 (Pa co2 − end-tidal carbon dioxide measurement) + 0.003 (respiratory rate per minute) + 0.0015 (age in years) on study days 1, 3 to 4, 6 to 9, and 14 after initiation of mechanical ventilation in adult patients who satisfied 1 of the 3 study defined diseases: (1) acute bacterial pneumonia, (2) acute respiratory distress syndrome, or (3) cystic fibrosis. Results Using the final/last available time point calculation of Vd/Vt, a significant difference was observed between survivors and nonsurvivors both in relation to mean and median values (56.5% vs 71.2% and 56.0% vs 65.0%, respectively). In addition, sequential analyses of Vd/Vt calculations over time also demonstrated a statistically significant difference between survivors and nonsurvivors for days 6 to 9. Conclusion In this study-specific population of critically ill patients, the prediction equation of Vd/Vt using clinically available parameters correlates with mortality. In addition, we provide a simple method to estimate Vd/Vt that can be potentially applicable to all critically ill intensive care unit patients.
Objective We sought to investigate the effect of body mass index (BMI) on in vitro response to tocolytics. Study Design Myometrial biopsies were obtained at the time of scheduled cesarean deliveries ...from term nonlaboring women with BMI ≤29.9 (26.3 ± 1.3; n = 7), 30-34.9 (31.8 ± 1.2; n = 16), and ≥35 (39.5 ± 4.9; n = 9). Tissue strips were suspended in organ chambers for isometric tension recording. The effects of cumulative doses (10−10 to 10−5 mol/L) of nifedipine or indomethacin on spontaneous uterine contractility were determined. Areas under the contraction curve were compared using 1-way analysis of variance with Tukey post hoc test. Results Myometrial response to tocolytics did not differ between the BMI groups. Nifedipine, but not indomethacin, significantly inhibited myometrial contractility independent of BMI. Conclusion BMI does not affect uterine response to tocolytics in isolated uterine tissue from term nonlaboring women.
To assess the pharmacodynamics and safety of alpha-1-proteinase inhibitor (human) (A1PI) isolated from pooled human plasma, a series of animal studies was conducted. Using both unlabeled and ...125I-labeled A1PI (highly purified), plasma residence time and tissue distribution were determined in rabbits. A catabolic half-life of 48.5 hours was obtained for the labeled material, which agreed well with the antigenic decay (35.5 hours), measured with a specific enzyme-linked immunosorbent assay, and the functional activity decay (38.1 hours), measured antigenically by the ability of resident human A1PI to complex with human neutrophil elastase. No unusual tissue distribution was observed at the first, 24th, or 168th hour of sacrifice. Cynomolgous monkeys received infusions of labeled A1PI and a catabolic half-life of 55.45 hours was obtained; infusion of unlabeled material yielded anticipated plasma recovery and a significant increment in A1PI in bronchial-alveolar lavage fluid, both antigenically and functionally determined. Safety studies assessing acute physiologic response and both acute and subacute toxicity presented no significant adverse effects. We conclude that A1PI (human) presents normal pharmacodynamics and safety and is therefore associated with a wide margin of safety for the intended clinical applications.
The aim of this study is to review the basic aspects of focal cerebral ischemia as a fundamental element in clinical practice and of neuroprotective strategies.
Ischemia triggers several different ...responses in nerve tissue which, according to the degree of energetic limitation, can be adaptive or lead to cell death due to necrosis or apoptosis. Establishing these processes is a complex task and the mechanisms involved have still not been fully explained; this is made more difficult by the fact that many of them are simultaneous and also because of the implications they may have, not only in cell death but also in the adaptation of the neurons that suffered ischemic stress and survived. We outline the foundations for understanding the physiopathological phenomena at work in ischemia: neuronal stress and death, and the reaction of the macroglial and microglial cells. This is also illustrated by original images from research into cell response to ischemia at a pre-clinical level in an experimental model of focal cerebral ischemia in rats, evaluated using, for example, hematoxylin-eosin and immunohistochemical techniques for several cell markers.
Cell death in ischemia is a complex phenomenon that can have two different outcomes: necrotic death or apoptotic death. Basic knowledge of the pathophysiology of ischemia and of the response of microglial and macroglial cells is the foundation for elaborating neuroprotective-type strategies, which must not only be oriented towards preventing acute cell death, but also later modes of cell death or strengthening the surviving tissue.
Charged-current neutrino interactions with low hadronic recoil ("low-nu") have a cross-section that is approximately constant versus neutrino energy. These interactions have been used to measure the ...shape of neutrino fluxes as a function of neutrino energy at accelerator-based neutrino experiments such as CCFR, NuTeV, MINOS and MINERvA. In this paper, we demonstrate that low-nu events can be used to measure parameters of neutrino flux and detector models and that utilization of event distributions over the upstream detector face can discriminate among parameters that affect the neutrino flux model. From fitting a large sample of low-nu events obtained by exposing MINERvA to the NuMI medium-energy beam, we find that the best-fit flux parameters are within their a priori uncertainties, but the energy scale of muons reconstructed in the MINOS detector is shifted by 3.6% (or 1.8 times the a priori uncertainty on that parameter). These fit results are now used in all MINERvA cross-section measurements, and this technique can be applied by other experiments operating at MINERvA energies, such as DUNE.
Research in animals has shown that early life experience, particularly parenting behaviors, influences later-life stress reactivity. Despite the tremendous relevance of this finding to human ...development and brain function, it has not been tested prospectively in humans. In this study two aspects of parenting were measured at age 4 in a sample of healthy, low socioeconomic status, African American children, and stress reactivity was measured in the same children 11-14 years later using a modified version of the Trier Social Stress Test (n = 55). Salivary cortisol was measured before, during and after the stressor and data were analyzed using piecewise hierarchical linear modeling. Parental responsivity, independent of the use of physical discipline, was positively related to cortisol reactivity. Effects were independent of subjective appraisals of the stressor and were also independent of other environmental risk factors and current psychosocial functioning. Therefore this study demonstrates in a novel and precise fashion that early childhood parental responsivity prospectively and independently predicts stress reactivity in adolescence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Phys.Rev.Lett. 131 (2023) 1, 011801 Neutrino-induced charged-current single $\pi^+$ production in the
$\Delta(1232)$ resonance region is of considerable interest to
accelerator-based neutrino ...oscillation experiments. In this work, high
statistics differential cross sections are reported for the semi-exclusive
reaction $\nu_\mu A \to \mu^- \pi^+ +$ nucleon(s) on scintillator, carbon,
water, iron, and lead targets recorded by MINERvA using a wide-band $\nu_\mu$
beam with $\left< E_\nu \right> \approx 6$~GeV. Suppression of the cross
section at low $Q^2$ and enhancement of low $T_\pi$ are observed in both light
and heavy nuclear targets compared to phenomenological models used in current
neutrino interaction generators. The cross-section ratios for iron and lead
compared to CH across the kinematic variables probed are 0.8 and 0.5
respectively, a scaling which is also not predicted by current generators.
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