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Biomedical subjects

M Barros

Publications and source records attributed to M Barros.

At least 19 recordsLinked to original sources

Personalized diagnosis by cached solutions with hypertension as a study model.

Statistical modeling of links between genetic profiles with environmental and clinical data to aid in medical diagnosis is a challenge. Here, we present a computational approach for rapidly selecting important clinical data to assist in medical decisions based on personalized genetic profiles. What could take hours or days of computing is available on-the-fly, making this strategy feasible to implement as a routine without demanding great computing power. The key to rapidly obtaining an optimal/nearly optimal mathematical function that can evaluate the "disease stage" by combining information of genetic profiles with personal clinical data is done by querying a precomputed solution database. The database is previously generated by a new hybrid feature selection method that makes use of support vector machines, recursive feature elimination and random sub-space search. Here, to evaluate the method, data from polymorphisms in the renin-angiotensin-aldosterone system genes together with clinical data were obtained from patients with hypertension and control subjects. The disease "risk" was determined by classifying the patients' data with a support vector machine model based on the optimized feature; then measuring the Euclidean distance to the hyperplane decision function. Our results showed the association of renin-angiotensin-aldosterone system gene haplotypes with hypertension. The association of polymorphism patterns with different ethnic groups was also tracked by the feature selection process. A demonstration of this method is also available online on the project's web site.

Algorithms↗

Rapid habituation of scan behavior in captive marmosets following brief predator encounters.

Scan behavior in 10 captive predator-naive adult black tufted-ear marmosets (Callithrix penicillata) was investigated prior, during and following brief predator encounters (taxidermized oncilla cat -- Leopardus tigrinus) versus neutral stimulus exposures (stuffed toy). For each stimulus, three 9 min home-cage trials were conducted > or = 72 h apart. Each trial was divided into three consecutive 3 min intervals: pre-exposure baseline observation, stimulus exposure, and post-exposure observation period. Post-exposure scan duration increased during the first two predator confrontations, while scan frequency increased significantly only after the first. Scan behavior remained constant within the last predator encounter, as it also did within and between the three neutral stimulus exposures. Although marmosets scanned more often and significantly longer after encountering the predator than the neutral stimulus, this response rapidly habituated by the second trial. Therefore, black tufted-ear marmosets in a familiar environment rapidly habituate to brief repeated predator encounters, possibly minimizing anti-predation costs once the degree of a potential threat has been adequately assessed.

Animals↗

Cocaine-induced 'active immobility' and its modulation by the serotonin1A receptor.

'Active immobility' (AI) is an independent behaviour that can be characterized by behavioural immobility, an increased muscular rigidity and the sustaining of an unusual posture. In previous studies with cocaine we observed, concomitant with hyperlocomotion and increased rearing activity, an increase in AI in well-habituated animals, which may constitute another 'positive' acute effect of cocaine on behaviour. The contribution of the serotonergic (5-HT) system to AI is well established. However, little information exists about the contribution of particular 5-HT-receptor subtypes. In order to examine a possible role of the 5-HT1A receptor on this effect of cocaine, we systematically re-analysed four previous experiments in well-habituated animals and one in little-habituated animals, focusing on the acute behavioural effects of cocaine on AI. We found that, in well-habituated animals, cocaine at a medium dose (10 mg/kg, i.p.) induces AI behaviour, which, however, does not correlate with cocaine effects on locomotion, rearing or grooming behaviour. However, there was no effect of cocaine (1, 5 or 15 mg/kg, i.p.) on AI in little-habituated animals. The 5-HT1A-receptor antagonist, WAY 100635 [N-[2-(4-2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide trihydrochloride] (0.4 mg/kg, i.p.), potentiated cocaine-induced AI in well-habituated animals, while the 5-HT1A-receptor agonist, 8-OH-DPAT (0.2 mg/kg, i.p.), attenuated it. The local application of 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] into the nucleus accumbens (0, 1, 10 micromol/l) or hippocampus (0, 0.1, 1, 10 micromol/l) modulated cocaine-induced AI in a complex way. These results showed that cocaine induces AI at a medium dose in well-habituated but not in little-habituated animals. The cocaine-induced AI in well-habituated animals can be potentiated by systemic 5-HT1A-receptor antagonism and attenuated by 5-HT1A-receptor agonism. Two experiments with local activation of postsynaptic 5-HT1A receptors revealed that both nucleus accumbens and hippocampal 5-HT1A-receptor populations are involved in the expression of cocaine-induced AI.

Animals↗

Evaluation of a rapid test (QuickVue) compared with the shell vial assay for detection of influenza virus clearance after antiviral treatment.

QuickVue influenza rapid diagnostic test (Quidel Corp., San Diego, CA, USA) was compared with the classical shell vial assay for evaluation of influenza virus clearance in patients treated with antiviral drugs. The shell vial assay was carried out on nasopharyngeal samples obtained from volunteers for a neuraminidase-inhibitor clinical trial protocol with 24 h or less from the onset of symptoms of influenza before the use of antiviral (day 1). Follow-up included samples collected after 24 and 72 h of therapy (day 2 and 4). The rapid test was retrospectively carried out in frozen samples. Test results on 99 samples from 33 adults were compared and the shell vial assay was considered the gold standard. The overall rate of detection for the shell vial assay was 39.4% and for QuickVue was 35.5%, with a concordance of 79.8%. The sensitivity obtained for QuickVue was 74.4% and the specificity was 82.7%. Comparison of test results day by day in the follow-up resulted: day 1, higher sensitivity of QuickVue test (85.5%, 24/29); day 2, agreement on positive and negative results between QuickVue and shell vial was 60.6% (20/33); day 4, all test results in samples collected after 72 h of therapy were negative. The QuickVue test showed good sensitivity for the diagnosis of influenza-like illnesses. This rapid test kit can be an alternative tool for interventions in disease management.

Adolescent↗

Features of the 3'-consensus sequence of rotavirus mRNAs critical to minus strand synthesis.

The last seven nucleotides of the 3'-end of rotavirus mRNAs, 5'-UGUGACC-3', are highly conserved and form a cis-acting signal that can promote the synthesis of (-) strand RNA to produce the viral dsRNA genome in vitro. Previous studies have shown that the sequence, location, and strandedness (single- versus double-stranded) of the 3'-consensus sequence of the mRNA affect the efficiency of (-) strand synthesis. In this study, we have used exhaustive mutagenesis of the SA11 gene 8 mRNA and an in vitro replication system to define the importance of each of the residues in the consensus sequence in (-) strand synthesis. The analysis showed that the CC of the consensus sequence was the most critical for (-) strand synthesis. Furthermore, the data revealed that other, but not all, residues of the consensus sequence contributed to efficient (-) strand synthesis in vitro. Mutant gene 8 RNAs supported an intermediate level of (-) strand synthesis when the 15 nt sequence upstream of the CC was replaced with long tracts of poly(A) or poly(U), but not with poly(G). Predictions of the secondary structure of the mutant RNAs suggested that the poly(G)-RNA could not replicate because its 3'-terminus was largely basepaired, instead of extending as a single-stranded tail as is the case for the 3'-termini of the poly(A)- and poly(U)-RNAs and wild-type gene 8 RNA. Subsequent experiments performed with complementary oligonucleotides indicated that efficient RNA replication occurs in vitro only when the last four residues of the 3'-consensus sequence, and most importantly the two terminal C's, existed in a single-stranded form. A single-stranded CC may be crucial for formation of an initiation complex for (-) strand synthesis consisting of viral RdRP, mRNA, and the dinucleotide pGpG.

Animals↗

Behavioral effects of buspirone in the marmoset employing a predator confrontation test of fear and anxiety.

In order to further validate the recently developed marmoset (Callithrix penicillata) predator confrontation model of fear and anxiety, we investigated the behavioral effects of buspirone with this method. The apparatus consisted of three parallel arms connected at each end to a perpendicular arm, forming a figure-eight continuous maze. A taxidermized wild oncilla cat (Felis tigrina) was positioned facing a corner of the parallel arms, alternating between the left or right side of the maze among animals tested. All subjects were first submitted to seven 30-min maze habituation trials (HTs) in the absence of the predator, and then to five randomly assigned treatment trials (TTs) in the presence of the predator: three buspirone sessions (0.1, 0.5 and 1.0 mg/kg), saline and sham injection controls. Twenty minutes after treatment administration, the animal was released into the maze and had free access to the apparatus for 30 min. All trials were taped for later behavioral analysis. Buspirone significantly decreased the frequency of scent marking, while increasing the time spent in proximity to the 'predator' stimulus, indicating an anxiolytic effect. Neither locomotor activity, exposure to a novel environment, stimulus location and habituation, nor gender influenced the effects of the drug treatments. These results further validate this method and demonstrate the potential usefulness of this ethologically based paradigm to test anxiety and fear-induced avoidance in nonhuman primates and its susceptibility to anxiolytic pharmacological manipulations.

Animals↗

Measuring fear and anxiety in the marmoset (Callithrix penicillata) with a novel predator confrontation model: effects of diazepam.

This report describes a new experimental method for measuring fear and anxiety in Cerrado marmosets (Callithrix penicillata). In order to test the sensitivity of the behavioral parameters to an anxiolytic substance, the effects of the benzodiazepine diazepam on the anxiety measures were examined. The strategy was to use a naturally occurring stimulus known to elicit anxiety and fear in this species. A taxidermized predator (the wild cat Felis tigrina) was chosen as the stimulus to induce anxiety-related behaviors on the basis of a preceding study in which various stimuli were systematically compared in their effectiviness to induce fear responses. The apparatus consisted of three parallel arms of equal dimensions, joining two perpendicular arms at each end, thus comprising a figure eight-like or five-arm continuous rectangular maze. The wild-cat was placed outside of one corner of the maze's outer parallel arms. Each subject was submitted to six treatments given in random order: three drug sessions (diazepam 1, 2 and 3 mg/kg, i.m.), saline, sham (injection control), and a control session, involving neither manipulation nor injection. Subjects were placed into the back of the chamber, out of sight of the 'predator', 20 min after a treatment and given free access to the maze for 30 min. The behavioral repertoire was recorded via videocamera. The following behaviors were considered to be possible indices of emotionality relevant to exposure to the predator in the paradigm used: scratching, scent marking, exploration, frequency and time spent in each of 13 defined sections of the maze. Administration of diazepam induced a significant reduction in scratching and an increase in the time spent in the vicinity of the 'predator', as well as in the frequency of exploratory behaviors, indicative of an anxiolytic effect. Gender did not influence the effect of treatment. These results suggest that this new ethologically-based test may be a useful method for studying anxiety and fear-induced avoidance in non-human primates and for pre-clinical research on psychoactive drugs.

Animals↗

[Respiratory symptoms and cough reflex in populations exposed to different degrees of environmental pollution].

BACKGROUND: Santiago is a city with a high degree of environmental pollution caused by particulate matter and ozone, producing adverse effects in the respiratory system. AIM: To compare respiratory symptoms and cough reflex in adults from Santiago and from a rural area with low levels of environmental pollution. SUBJECTS AND METHODS: One hundred twenty six non-smoker adults from Santiago and 116 from a rural area with low levels of pollution answered a respiratory symptom questionnaire. Of these 101 subjects from Santiago and 116 from the rural area inhaled doubling concentrations of capsaicin from 0.5 to 500 microM or until five coughs were elicited. The lowest concentration eliciting 2 or more coughs (CD2) or 5 or more coughs (CD5) was recorded. Levels of environmental particulate matter were also recorded in both locations. RESULTS: Levels of particulate matter were 102 +/- 41 and 64 +/- 24 micrograms/m3 in Santiago and the rural area respectively. People from Santiago had higher rates of throat clearing, cough and phlegm. CD2 geometric mean and confidence limits in Santiago and the rural area were 6.9 (5.2-7.4) and 2.8 (2.7-2.9) respectively (p < 0.001). No differences in CD5 were observed between both locations. Multivariate analysis disclosed the variable location (city) as the only independent predictor of respiratory symptoms. CONCLUSIONS: The increased CD2 found in Santiago suggests that the higher rates of respiratory symptoms related to air pollution can be associated to a decreased sensitivity of the cough reflex.

Adolescent↗

[Intermittent negative pressure ventilation in patients with chronic air flow limitation: criteria for selection of patients].

To determine clinical and functional predictive criteria for use of intermittent negative pressure ventilation we evaluated 9 patients with severe chronic air flow limitation. Arterial blood gases, lung volumes, maximal inspiratory pressures and transdiaphragmatic pressure during quiet breathing were measured. patients were then ventilated once or twice a week for 3 to 10 weeks and improvement was evaluated through changes in quality of life, dyspnea, PaO2, PaCO2 and maximal inspiratory mouth pressure (PRMAX). Result was considered good when 4 or more of these indices improved. 5 patients benefitted from intermittent negative pressure ventilation. Compared to non responders, patients who improved had significantly lower PRMAX (39.4 +/- 11.6 VS 73.5 +/- 13.8 CMh20, p < 0.025), and higher percentage of their maximal inspiratory pressure during quiet breathing (31.2 +/- 7 vs 12.2 +/- 5%, p < 0.025>). Other indices were not different between groups. We conclude that a severe impairment of inspiratory muscle function characterizes patients with chronic air flow limitation who may benefit from intermittent negative pressure ventilation.

Adult↗

Site of action of nitrofurantoin in experimental urinary tract infection.

The effectiveness of nitrofurantoin in suppressing bacterial growth in the urinary tract was evaluated by using two different experimental models. Pyelonephritis was produced in rats by direct inoculation of 10(4)Escherichia coli in the medulla of left kidney. Ascending urinary tract infection was induced by inoculation into the urinary bladder of 10(7)Proteus mirabilis, after a partial cystectomy. Nitrofurantoin was shown to be effective in suppressing bladder bacteriuria, in preventing ascending pyelonephritis, and also in preventing bacterial multiplication in kidney tissue following direct inoculation.

Animals↗