Effects of Cycloleucine in the Nucleus Accumbens Septi on the Elevated plus Maze Test in Rats.

INTRODUCTION: In recent years, an important number of studies have emphasized the psychopharmacological actions of cycloleucine (1-aminocyclopentanecarboxylic acid) acting on the NR1 subunit (glycine allosteric site) of NMDA (N-methyl-D-aspartic acid) receptor. We studied the effects of its injection in an anxiety test. METHODS: The elevated plus maze test was used. Male rats bilaterally cannulated into the nucleus accumbens septi (NAS) were employed. Rats were divided into 5 groups that received either 1 µL injections of saline or cycloleucine (0.5, 1, 2, or 4 µg) 15 min before testing. RESULTS: Time spent in the open arm was significantly increased by cycloleucine treatment with all doses (1 and 2 µg, p < 0.05; 0.5 and 4 µg, p < 0.01), like number of extreme arrivals (0.5 and 1 µg, p < 0.05; 2 µg, p < 0.01; and 4 µg, p < 0.001). Open arm entries were increased by the highest dose only (4 µg, p < 0.01). DISCUSSION/CONCLUSION: Present results show no difference between all doses in the time spent in the open arm, suggesting an indirect, noncompetitive action of the drug. The increase in extreme arrivals and open arm entries suggests a dose influence in these parameters. We conclude that cycloleucine influence on the NMDA receptors within NAS leads to anxiolytic-like effects and behavioral disinhibition, which once more confirms the involvement of NAS in anxiety processing.

Prediction of neonatal death in pregnant women in an intensive care unit: Application of machine learning models.

Introduction: Neonatal mortality remains a critical concern, particularly in developing countries. The advent of machine learning offers a promising avenue for predicting the survival of at-risk neonates. Further research is required to effectively deploy this approach within distinct clinical contexts. Objective: This study aimed to assess the applicability of machine learning models in predicting neonatal mortality, drawing from maternal and clinical characteristics of pregnant women within an intensive care unit (ICU). Methods: Conducted as an observational cross-sectional study, the research enrolled pregnant women receiving care in a level III national hospital's ICU in Peru. Detailed data encompassing maternal diagnosis, maternal characteristics, obstetric characteristics, and newborn outcomes (survival or demise) were meticulously collected. Employing machine learning, predictive models were developed for neonatal mortality. Estimations of beta coefficients in the training dataset informed the model application to the validation dataset. Results: A cohort of 280 pregnant women in the ICU were included in this study. The Gradient Boosting approach was selected following rigorous experimentation with diverse model types due to its superior F1-score, ROC curve performance, computational efficiency, and learning rate. The final model incorporated variables deemed pertinent to its efficacy, including gestational age, eclampsia, kidney infection, maternal age, previous placenta complications accompanied by hemorrhage, severe preeclampsia, number of prenatal checkups, and history of miscarriages. By incorporating optimized hyperparameter values, the model exhibited an impressive area under the curve (AUC) of 0.98 (95 % CI: 0.95-1), along with a sensitivity of 0.98 (95 % CI: 0.94-1) and specificity of 0.98 (95 % CI: 0.93-1). Conclusion: The findings underscore the utility of machine learning models, specifically Gradient Boosting, in foreseeing neonatal mortality among pregnant women admitted to the ICU, even when confronted with maternal morbidities. This insight can enhance clinical decision-making and ultimately reduce neonatal mortality rates.

[A multidisciplinary program for the treatment and follow up of depression in ambulatory elderly]. / Ensayo pragmático para evaluar la efectividad de un programa de manejo de depresión para pacientes mayores de 65 años en un Plan de Salud.

Depression is a common disorder in the elderly population; with significant elevated rates in terms of morbidity and mortality. Nonetheless it continues to be a subdiagnosticated disease with poor outcomes due to lack in the effectiveness of follow up. We developed collaborative intervention programs for elderly people in primary care at Hospital Italiano de Buenos Aires designing a randomized controlled trial in the ambulatory setting. Patients were recruited for an initial comprehensive geriatric evaluation, and then randomly assigned to the program intervention (n=18) or usual care (n=19). At 6 months, 55.5% of intervention patients had a 50% or greater reduction in depressive symptoms from baseline compared with 31.5% of those on usual care. Although the reduction of the outcomes of depressive symptoms is not statistically significative, these are preliminary data. We believe there is a trend toward better results with regard to improvements in depressive symptoms in patients in the intervention group, and that this will achieve statistical significance as the number of subjects recruited is increased in the course of the trial.

Deep hypothermia prevents striatal alterations produced by perinatal asphyxia: Implications for the prevention of dyskinesia and psychosis.

GABAergic medium spiny neurons are the main neuronal population in the striatum. Calbindin is preferentially expressed in medium spiny neurons involved in the indirect pathway. The aim of the present work is to analyze the effect of perinatal asphyxia on different subpopulations of GABAergic neurons in the striatum and to assess the outcome of deep therapeutic hypothermia. The uterus of pregnant rats was removed by cesarean section and the fetuses were exposed to hypoxia by immersion in water (19 min) at 37°C (perinatal asphyxia). The hypothermic group was exposed to 10°C during 30 min after perinatal asphyxia. The rats were euthanized at the age of one month (adolescent/adult rats), their brains were dissected out and coronal sections were immunolabeled for calbindin, calretinin, NeuN, and reelin. Reelin+ cells showed no staining in the striatum besides subventricular zone. The perinatal asphyxia (PA) group showed a significant decrease in calbindin neurons and a paradoxical increase in neurons estimated by NeuN staining. Moreover, calretinin+ cells, a specific subpopulation of GABAergic neurons, showed an increase caused by PA. Deep hypothermia reversed most of these alterations probably by protecting calbindin neurons. Similarly, there was a reduction of the diameter of the anterior commissure produced by the asphyxia that was prevented by hypothermic treatment.

Emotional salience enhances intelligibility in adverse acoustic conditions.

INTRODUCTION: Emotion facilitates word recognition under adverse acoustic conditions. We use an auditory emotional paradigm to evaluate the ability to distinguish words from irrelevant random stimuli, elucidating its neural correlates. Secondarily, we evaluate the impact of schizotypy traits on this capacity. METHODS: 25 participants, undertook an fMRI task, indicating whether they recognized words, through a response box. 20 audio files of emotionally negative words and 20 neutral words were presented. Word intelligibility was manipulated merging the audio files with white noise at varying signal-to-noise ratios (SNR), resulting in 3 levels (high, medium, and low). We measured schizotypy with the O-LIFE scale. RESULTS: A 2x3 factorial ANOVA was performed with emotion (neutral or negative) and intelligibility (high, medium, and low) as factors. There was an interaction between emotion and intelligibility [F(2,44) = 23.89,p<0.001]. Post hoc t-test demonstrated that, in medium and low intelligibility, negative words were more recognized than neutral ones. Negative words minus neutral, activated the right anterior cingulate cortex (rACC), right dorsolateral prefrontal cortex (rDLPFC), and right orbitofrontal cortex (rOFC). Low compared to high intelligibility, activated the left medial temporal gyrus (lMTG), left supramarginal gyrus (lSMG), and left angular gyrus (lAG). Medium compared with high intelligibility, activated the left temporal pole (lTP) and the lMTG. There were correlations between schizotypy and rACC, lMTG, and rOFC activations. DISCUSSION: Negative emotional salience improves intelligibility, possibly by recruiting selective attention. Less intelligible stimuli activated temporo-parietal regions related to speech processing in adverse acoustic conditions, while emotionally negative stimuli activated areas associated with emotional processing (rACC and rOFC) and selective attention (rDLPFC). High schizotypy correlated with greater responses in rACC, lMTG, and rOFC, during low intelligibility. Irrelevant emotionally salient stimuli would capture automatic attention activating rACC and rOFC, enhancing speech comprehension through additional recruitment of lMTG, which could derive in false word recognition.

Deep hypothermia reverses behavioral and histological alterations in a rat model of perinatal asphyxia.

The consequences of perinatal asphyxia (PA) include alterations which may manifest as schizophrenia. Characteristic features of this disease include a decrease in specific subpopulations of GABAergic cells and deterioration of social interaction. The purpose of this study is to assess if a deep and short-hypothermic treatment can ameliorate this damage in a model of PA. Rats offsprings were exposed to 19 min of asphyxia by immersing the uterus horns in water at 37 °C followed by 30 min in air at 10 °C that resulted in 15 °C body temperature. At postnatal day 36-38, the rats were tested in the open field and social interaction paradigms and processed for immunostaining of calbindin and reelin. A brief exposure to deep hypothermia reversed the deterioration produced by PA in play soliciting. PA decreased the density of calbindin neurons in layer II of the Anterior Insular Cortex, while deep hypothermia reversed this effect. Paradoxically, in AIC, there was a significant increase in the number of reelin-secreting neurons in layers II and III generated by PA and this increase was reversed by hypothermia. This suggests a compensatory mechanism, where reelin neurons trend to compensate for the loss of calbindin neurons, at least within Anterior Insular Cortex. Finally, the deep hypothermic shock might represent a valuable therapeutic alternative to treat PA.

Effects of dizocilpine-induced glutamatergic blockade in the nucleus accumbens septi on the plus maze test.

BACKGROUND: In previous studies, we have observed that specific N-methyl-d-aspartic acid (NMDA) antagonists and non-NMDA antagonists injected within the nucleus accumbens septi (NAS) induced an anxiolytic-like effect in the plus maze test in rats. In the present study, the effect of intracanalicular blockade of NMDA receptors using dizocilpine in the plus maze was studied in male rats bilaterally cannulated NAS. METHODS: Rats were divided into five groups that received either 1 µL injections of saline or dizocilpine (MK-801, [5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine) in different doses (0.5, 1, 2, or 4 µg) 15 min before testing. RESULTS: Time spent in the open arm increased under dizocilpine treatment with the two higher doses (2 and 4 µg, p<0.05), extreme arrivals were increased by the three higher doses (1 µg, p<0.05; 2 and 4 µg, p<0.01), and open arm entries by the three higher doses (1, 2, and 4 µg, p<0.05). A dose-effect relationship was observed in all cases. CONCLUSIONS: We conclude that dizocilpine-glutamatergic blockade in the accumbens lead to an anxiolytic-like effect and a behavioral disinhibition related to an increase in some motoric parameters, showing specific behavioral patterns.