We investigated sequence-learning skills in 64 children with cerebral palsy (aged 4.01-14.7 years; 49 with bilateral, two with dystonic, and 13 with unilateral cerebral palsy), compared with a ...matched control group of typically developing children. Participants’ motor and handling abilities were classified according to the Gross Motor Function Classification System and the Manual Ability Classification System. General cognitive, visuoperceptual, and constructive abilities were assessed. Participants performed an experimental computerized version of Corsi Span, followed by a normalized Supraspan sequence. Controls outperformed cerebral palsy participants in visual memory and accuracy. Participants with cerebral palsy were likelier to fail the test (cerebral palsy, 37.5%; control subjects, 5%) and obtain overall lower scores. Sequence learning skills were not related to motor and handling impairments. Failure to learn sequences resulted in an overall lower functioning profile regarding visuoperceptual, verbal, and performance abilities. The ability to fix sequences seemed to split the cerebral palsy group into an overall high-functioning group (successful in sequence learning) and low-functioning (failing) group. Results are discussed in light of a specific implicit memory impairment and the abnormal development of white matter frontostriatal and parietal connections.
The antiemetic activity of DAU 6215, a novel antagonist of 5-HT3 receptors, was investigated in animal models of cytotoxic treatment-evoked emesis and compared with the antiemetic activity of ...ondansetron and metoclopramide. In dogs, vomiting was induced by i.v. cisplatin; in ferrets, the emetic response was elicited by i.v. doxorubicin or X-ray exposure. Pretreatment with 0.1-1 mg/kg DAU 6215 given i.v. or p.o. prevented the vomiting response to the different emetic agents. In the dog, the antiemetic potency of metoclopramide was 30 times lower than that of DAU 6215. Ondansetron was less potent than DAU 6215 against cisplatin and doxorubicin but was equally effective in the radiotherapy protocol. In this model, lengthening of the pretreatment time to 2 h did not affect the antiemetic efficacy of DAU 6215, whereas it decreased that of ondansetron. The results demonstrate that DAU 6215 is a highly effective and long-lasting inhibitor of cytotoxic treatment-induced emesis in different animal species.
The feasibility and effectiveness of a year-long integrated rehabilitation program for young children (less than 6 years old) with cerebral palsy was evaluated, and efficacy of different treatment ...schedules was compared. A sample of 40 children (20 male; mean age, 3 years ±1.22) took part: 20 presented with tetraparesis, 12 with diparesis, and 8 with hemiparesis. Participants' motor abilities were classified according to the Gross Motor Function Measure classification system at baseline and after 1 year of treatment. For half of the participants, treatment consisted of continuous integrated intervention twice a week; for the other half, treatment was the 3i intervention (Intermittent, Intensive, Integrated), in which a month of intensive, twice-a-day treatment was followed by a continuous, twice-a-week phase, lasting 5 months. Overall, there was an improvement in gross motor function, with 37% of children improving and no children showing lowered function. Neither baseline general cognitive abilities nor age had a significant effect on the level of improvement, although initial gross motor function did. Children undergoing the intensive intermittent intervention showed the greatest motor function improvement. Results support the effectiveness of the integrated intervention and of periods of higher frequency intervention in young children.
Using a spectrally resolved electron interferometry technique, we measure photoionization time delays between the \(3s\) and \(3p\) subshells of argon over a large 34-eV energy range covering the ...Cooper minima in both subshells. The observed strong variations of the \(3s-3p\) delay difference, including a sign change, are well reproduced by theoretical calculations using the Two-Photon Two-Color Random Phase Approximation with Exchange. Strong shake-up channels lead to photoelectrons spectrally overlapping with those emitted from the \(3s\) subshell. These channels need to be included in our analysis to reproduce the experimental data. Our measurements provide a stringent test for multielectronic theoretical models aiming at an accurate description of inter-channel correlation.
A series of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic acid esters and amides containing a basic azacyclo- or azabicycloalkyl moiety has been synthesized and evaluated for 5-HT3 antagonistic ...activity in a radioligand binding assay (3HICS 205930) and in the 5-HT-induced von Bezold-Jarisch reflex in the rat. It was found that endo-substituted azabicycloalkyl derivatives (e.g. 7a, 12a, 12b) were much more active than the corresponding exo analogues (e.g. 7b, 12h, 12i) or azacycloalkyl compounds. Amidic derivatives 12a, 12b, 12c, 12e, 13b, and 13c proved to be about 10 times more active than the corresponding ester derivatives 7a, 11a, 7c, 7d, 8a, and 8b. In particular, compound 12a (DA 6215) showed a Ki = 3.8 nM in the binding test and an ED50 = 1 nM/kg iv in the von Bezold-Jarisch reflex assay, an activity comparable to that of the reference compound 2 (ICS 205930, Ki = 2 nM, ED50 = 2.1 nM/kg). IR spectroscopy studies in the solid state and in CHCl3 solution revealed the existence of an intramolecular hydrogen bond in 13b, taken as a model compound for this class of substances. A molecular modeling study showed that 12a, in its internal hydrogen-bound conformation, well matches a recently proposed pharmacophoric model for 5-HT3 antagonist activity.
Excitability is a property of many nonlinear dynamical systems which is defined by the response of the system to external perturbations. A system is said to be excitable if a small perturbation leads ...to a linear response (which depends on the perturbation itself) while a large enough perturbation, above a certain threshold, leads to a response which does not depend on the perturbation. This precise property is key to the operation of many biological systems and in particular to the information processing capabilities of ensambles of neural cells: in such a system information is encoded in the temporal pattern of the pulses and not in their precise shape or amplitude. From this point of view, the realization and the control of excitable systems based on semiconductor lasers (fast, robust and versatile elements of many present and future key technologies) may bring to optical telecommunications systems functionalities typical of neural cells such as thresholding and signal restoration. In spite of many theoretical 1 or experimental 2,3 investigations devoted to the excitable character of lasers with injected signal, no experimental demonstration for the control of excitable pulses in injected semiconductor lasers has been reported yet. In the present contribution, we show that excitable pulses can be triggered by applying suitable perturbations in either the bias current of the device or in the injected beam parameters.
A series of malonamic acid esters with suitable amino alcohols, typical of antimuscarinic compounds, was synthesized and the affinities for the three pharmacologically defined muscarinic receptor ...subtypes, namely M1, M2 and M3, were evaluated by radioligand displacement experiments. It was found that the esters with 3-quinuclidinol 7b, 7f-g, 8 and 9 are ligands with intermediate to high affinity for the M1 receptors, for which they show a preferential binding. Unexpectedly, the ester 7a with tropine bound with negligible affinity to all the receptors investigated. The introduction of a phenyl group on the carboxamido moiety of 7b gave compound 9, which showed an affinity for the M1 receptor comparable with that of the reference drug Pirenzepine 1.
BACKGROUNDChanges in flow to the gut and the kidney during hemorrhage and resuscitation contribute to organ dysfunction and outcome. We evaluated regional and splanchnic oxygen (O2) flow distribution ...and calculated oxygen supply distribution during hemorrhage and reperfusion and compared them with global measures.
METHODSSeven anesthetized pigs were instrumented to evaluate global hemodynamics, visceral blood flow, and oxygen transport. Tonometric pH probes were positioned in the stomach and jejunum. Animals were bled to 45 mm Hg for 1 hour. Crystalloids and blood were infused during the following 2 hours to normalize blood pressure, heart rate, urine output, and hemo- globin.
RESULTSDuring hemorrhage, mesenteric flow and O2 consumption were significantly decreased, whereas systemic consumption remained normal. Renal flow was reduced, but renal O2 consumption remained normal. After resuscitation, despite normal hemodynamics, neither systemic, mesenteric, nor renal O2 delivery returned to baseline. Lactate remained significantly increased. Arterial pH, base excess, and gastric and jejunal pH were all de- creased.
CONCLUSIONDuring hemorrhage, the gut is more prone than other regions to O2 consumption supply dependency. After resuscitation, standard clinical parameters do not detect residual O2 debt. Lactate, arterial pH, base excess, and intramucosal gut pH are all markers of residual tissue hypoperfusion.
Autoionization, which results from the interference between direct photoionization and photoexcitation to a discrete state decaying to the continuum by configuration interaction, is a well known ...example of the important role of electron correlation in light-matter interaction. Information on this process can be obtained by studying the spectral, or equivalently, temporal complex amplitude of the ionized electron wavepacket. Using an energy-resolved interferometric technique, we measure the spectral amplitude and phase of autoionized wavepackets emitted via the sp2+ and sp3+ resonances in helium. These measurements allow us to reconstruct the corresponding temporal profiles by Fourier transform. In addition, applying various time-frequency representations, we observe the build up of the wavepackets in the continuum, monitor the instantaneous frequencies emitted at any time and disentangle the dynamics of the direct and resonant ionization channels.
