Learning and assessment strategies to develop specific and transversal competencies for a humanized medical education.

Introduction: Medical education should promote the development of skills and abilities that can be applied to real-world work performance. The aim of this study is to evaluate technical and methodological knowledge, as well as physician-patient communication skills, as one of the most important transversal competencies that a good physician should acquire; all this in a reliable, accurate and objective way. Methods: We present a rubric specifically designed and implemented for the evaluation of specific and transversal competencies in the physiology practical sessions, during the second year of the medical degree. The assessment consists in two evaluation tests: 1) a theoretical test that consists of multiple-choice questions. Students must demonstrate that they have acquired adequate theoretical knowledge (specific competency "to know"); 2) a practical test, in which students are evaluated by the rubric through the simulation of a medical consultation. Thus, demonstrating their ability to execute/apply what they have learned in class (specific competency "to know how to do"). They are also evaluated on the transversal competencies that we call "communication with the patient" (transversal competency "to know how to be there") and "dealing with the patient" (transversal competency "to know how to be"). Results: We evaluated whether there were differences in the grades obtained by students when the transversal competencies were not assessed (academic years 2017-2018 and 2018-2019; n = 289), and when the transversal competencies were assessed by applying the rubric in the academic years 2019-2020, 2021-2022, and 2022-2023 (n = 526). Furthermore, we present a student perception that supports the use of clinical simulation and our rubric as a good method within the competency learning process. Discussion: The acquisition of these competencies, starting from the first courses of undergraduate education, helps to raise the students' awareness in the development of a more humanized medicine, allowing a better response to the patients' needs. Our rubric, which clearly indicate the performance criteria, have become an excellent method to carry out the assessment of competencies, both for students and teachers, since they allow to obtain clear evidence of the level of acquisition and application of knowledge.

Distinct Temporal Coordination of Spontaneous Population Activity between Basal Forebrain and Auditory Cortex.

The basal forebrain (BF) has long been implicated in attention, learning and memory, and recent studies have established a causal relationship between artificial BF activation and arousal. However, neural ensemble dynamics in the BF still remains unclear. Here, recording neural population activity in the BF and comparing it with simultaneously recorded cortical population under both anesthetized and unanesthetized conditions, we investigate the difference in the structure of spontaneous population activity between the BF and the auditory cortex (AC) in mice. The AC neuronal population show a skewed spike rate distribution, a higher proportion of short (≤80 ms) inter-spike intervals (ISIs) and a rich repertoire of rhythmic firing across frequencies. Although the distribution of spontaneous firing rate in the BF is also skewed, a proportion of short ISIs can be explained by a Poisson model at short time scales (≤20 ms) and spike count correlations are lower compared to AC cells, with optogenetically identified cholinergic cell pairs showing exceptionally higher correlations. Furthermore, a smaller fraction of BF neurons shows spike-field entrainment across frequencies: a subset of BF neurons fire rhythmically at slow (≤6 Hz) frequencies, with varied phase preferences to ongoing field potentials, in contrast to a consistent phase preference of AC populations. Firing of these slow rhythmic BF cells is correlated to a greater degree than other rhythmic BF cell pairs. Overall, the fundamental difference in the structure of population activity between the AC and BF is their temporal coordination, in particular their operational timescales. These results suggest that BF neurons slowly modulate downstream populations whereas cortical circuits transmit signals on multiple timescales. Thus, the characterization of the neural ensemble dynamics in the BF provides further insight into the neural mechanisms, by which brain states are regulated.

Dopaminergic modulation of tonic but not phasic GABAA-receptor-mediated current in the ventrobasal thalamus of Wistar and GAERS rats.

Activation of GABA(A) receptors by GABA causes phasic and tonic conductances in different brain areas. In the ventrobasal (VB) thalamus, tonic inhibition originates from GABA acting on extrasynaptic receptors. Here we show that dopamine (DA), the D2-like agonist quinpirole and the selective D4R agonist PD-168,077 decrease the magnitude of the tonic GABA(A) current while D1-like agonist SKF39383 lacks any significant effects in VB neurons of Wistar rats. On the other hand, DA and D1/D2 receptor activation does not alter phasic GABA(A) conductance. As we previously reported that an increased tonic GABA(A) current in VB neurons is critical for absence seizure generation, we also investigated whether D2-D4 receptor activation is capable of normalizing this aberrant conductance in genetic absence epilepsy rats from Strasbourg (GAERS). Quinpirole and PD-168,077 selectively reduces tonic GABA(A) current as in normal rats. Therefore, it is conceivable that some DA anti-absence effects occur via modulation of tonic GABA(A) current in the VB.

Spinal cord injury immediately changes the state of the brain.

Spinal cord injury can produce extensive long-term reorganization of the cerebral cortex. Little is known, however, about the sequence of cortical events starting immediately after the lesion. Here we show that a complete thoracic transection of the spinal cord produces immediate functional reorganization in the primary somatosensory cortex of anesthetized rats. Besides the obvious loss of cortical responses to hindpaw stimuli (below the level of the lesion), cortical responses evoked by forepaw stimuli (above the level of the lesion) markedly increase. Importantly, these increased responses correlate with a slower and overall more silent cortical spontaneous activity, representing a switch to a network state of slow-wave activity similar to that observed during slow-wave sleep. The same immediate cortical changes are observed after reversible pharmacological block of spinal cord conduction, but not after sham. We conclude that the deafferentation due to spinal cord injury can immediately (within minutes) change the state of large cortical networks, and that this state change plays a critical role in the early cortical reorganization after spinal cord injury.

Aromatase expression in the normal and epileptic human hippocampus.

Aromatase is a key enzyme in estrogen biosynthesis that is involved in neuronal plasticity in the rodent hippocampus. Although aromatase mRNA expression has been detected in the human hippocampus, its cellular distribution has yet to be determined. Here, we have examined the immunohistochemical distribution of aromatase in the normal and the epileptic and sclerotic human hippocampus. In both the normal and epileptic hippocampus, aromatase was detected in numerous CA1-CA3 pyramidal neurons, in granule cells of the dentate gyrus and in interneurons that co-expressed the calcium-binding proteins calbindin, calretinin or parvalbumin. However, only a small subpopulation of astrocytes was immunoreactive for aromatase in either the normal and epileptic hippocampus. The widespread expression of aromatase in a large population of neurons in the normal and damaged hippocampus suggests that local estrogen formation may play an important role in human hippocampal function.

Selective transcriptional regulation of aromatase gene by vitamin D, dexamethasone, and mifepristone in human glioma cells.

The human aromatase gene (CYP19A1) is controlled by multiple promoters that give rise to different aromatase transcripts. Its regulation has been studied in cells from multiple origins, including placenta, bone, adipose tissue, and breast cancer. However, little is known about its regulation in cells from neural origin. We assessed whether vitamin D, dexamethasone, and the glucocorticoid receptor antagonist mifepristone regulate the aromatase gene in human glioma, neuroblastoma, and breast cancer cells. The results show that these compounds enhance the activity of different aromatase promoters in glioma cells, but not in neuroblastoma and breast cancer cells. Vitamin D increased the expression of I.3, I.7, and I.4 aromatase transcripts and induced de novo expression of the I.6 transcript; dexamethasone increased the expression of I.4, PII, and I.3 transcripts and mifepristone increased the expression of PII and I.3 aromatase transcripts. The cell specific regulation of CYP19A1 by vitamin D, dexamethasone, and mifepristone opens the possibility for cellular selective modulation of estrogen biosynthesis within the brain.

Aromatase distribution in the monkey temporal neocortex and hippocampus.

Numerous studies have shown that neuronal plasticity in the hippocampus and neocortex is regulated by estrogen and that aromatase, the key enzyme for estrogen biosynthesis, is present in cerebral cortex. Although the expression pattern of aromatase mRNA has been described in the monkey brain, its precise cellular distribution has not been determined. In addition, the degree to which neuronal aromatase is affected by gonadal estrogen has not been investigated. In this study, we examined the immunohistochemical distribution of aromatase in young ovariectomized female rhesus monkeys with or without long-term cyclic estradiol treatment. Both experimental groups showed that aromatase is localized in a large population of CA1-3 pyramidal cells, in granule cells of the dentate gyrus and in some interneurons in which it was co-expressed with the calcium-binding proteins calbindin, calretinin, and parvalbumin. Moreover, numerous pyramidal cells were immunoreactive for aromatase in the neocortex, whereas only small subpopulations of neocortical interneurons were immunoreactive for aromatase. The widespread expression of the protein in a large neuronal population suggests that local intraneuroral estrogen synthesis may contribute to estrogen-induced synaptic plasticity in monkey hippocampus and neocortex of female rhesus monkeys. In addition, the apparent absence of obvious differences in aromatase distribution between the two experimental groups suggests that these localization patterns are not dependent on plasma estradiol levels.

Ro5-4864, a synthetic ligand of peripheral benzodiazepine receptor, reduces aging-associated myelin degeneration in the sciatic nerve of male rats.

The peripheral-type benzodiazepine receptor (PBR) is a protein predominantly located in the mitochondrial outer membrane that plays an important role in the regulation of cell survival and proliferation. Previous studies have shown an enhanced expression of PBR in the regenerating sciatic nerve, suggesting that this protein may be involved in the regenerative response. The rat sciatic nerve suffers important structural alterations with aging, including alterations in the morphology of myelin sheaths and a decrease in the number of myelinated fibers. In this study, we have assessed the effect of two PBR ligands, Ro5-4864 and PK-11195, to determine whether PBR may influence aging-associated morphological changes in the sciatic nerve. The treatment of 23-month-old, Sprague-Dawley male rats for 1 month with Ro5-4864 significantly reduced the percentage of fibers with myelin decompaction and increased the total number of myelinated fibers. In contrast, PK-11195, a PBR ligand that binds to a different site than Ro5-4864 in the PBR molecule, did not significantly affect any of the parameters analyzed. These findings support the potential role of PBR ligands to prevent aging-associated peripheral nerve degeneration.

Aromatase, the enzyme responsible for estrogen biosynthesis, is expressed by human and rat glioblastomas.

The biosynthesis of estradiol and related estrogens is catalyzed by the enzyme aromatase. Among other tissues, aromatase is expressed in the brain, where it is involved in the regulation of neuroendocrine events and reproduction. Under physiological conditions, the expression of aromatase in the mammalian brain is restricted to neurons. However, recent studies have shown that reactive astrocytes express aromatase after brain injury. This opens the possibility for the expression of the enzyme in other altered forms of glial cell, such as gliomas. In the present study, the expression of aromatase has been assessed, by RT-PCR and immunocytochemistry, in the rat glioblastoma C6 and in two human glioblastoma cell lines T98G and U373MG. The three cell lines expressed aromatase mRNA and showed a cytoplasmic pattern of aromatase immunoreactivity. In addition, the three cell lines express estrogen receptor alpha, suggesting that estradiol formed by aromatase may act as an autocrine or paracrine factor for glioblastoma cells. By analogy to the implication of aromatase into the growth of other forms of estrogen-sensitive tumors, such as some breast cancers, it is conceivable that the expression of aromatase may play a role in the growth of glioblastomas.