Kisspeptin signaling in astrocytes modulates the reproductive axis.

Reproduction is safeguarded by multiple, often cooperative regulatory networks. Kisspeptin signaling, via KISS1R, plays a fundamental role in reproductive control, primarily by regulation of hypothalamic GnRH neurons. We disclose herein a pathway for direct kisspeptin actions in astrocytes that contributes to central reproductive modulation. Protein-protein-interaction and ontology analyses of hypothalamic proteomic profiles after kisspeptin stimulation revealed that glial/astrocyte markers are regulated by kisspeptin in mice. This glial-kisspeptin pathway was validated by the demonstrated expression of Kiss1r in mouse astrocytes in vivo and astrocyte cultures from humans, rats and mice, where kisspeptin activated canonical intracellular signaling-pathways. Cellular co-expression of Kiss1r with the astrocyte markers, GFAP and S100-ß, occurred in different brain regions, with higher percentage in Kiss1- and GnRH-enriched areas. Conditional ablation of Kiss1r in GFAP-positive cells, in the G-KiRKO mouse, altered gene expression of key factors in PGE2 synthesis in astrocytes, and perturbed astrocyte-GnRH neuronal appositions, as well as LH responses to kisspeptin and LH pulsatility, as surrogate marker of GnRH secretion. G-KiRKO mice also displayed changes in reproductive responses to metabolic stress induced by high-fat diet, affecting female pubertal onset, estrous cyclicity and LH-secretory profiles. Our data unveil a non-neuronal pathway for kisspeptin actions in astrocytes, which cooperates in fine-tuning the reproductive axis and its responses to metabolic stress.

Low-Density Lipoproteins Increase Proliferation, Invasion, and Chemoresistance via an Exosome Autocrine Mechanism in MDA-MB-231 Chemoresistant Cells.

Dyslipidemias involving high concentrations of low-density lipoproteins (LDLs) increase the risk of developing triple-negative breast cancer (TNBC), wherein cholesterol metabolism and protein translation initiation mechanisms have been linked with chemoresistance. Doxorubicin (Dox) treatment, a member of the anthracycline family, represents a typical therapeutic strategy; however, chemoresistance remains a significant challenge. Exosomes (Exs) secreted by tumoral cells have been implicated in cell communication pathways and chemoresistance mechanisms; the content of exosomes is an outcome of cellular cholesterol metabolism. We previously induced Dox resistance in TNBC cell models, characterizing a variant denominated as variant B cells. Our results suggest that LDL internalization in parental and chemoresistant variant B cells is associated with increased cell proliferation, migration, invasion, and spheroid growth. We identified the role of eIF4F translation initiation factor and the down-regulation of tumor suppressor gene PDCD4, an inhibitor of eIF4A, in chemoresistant variant B cells. In addition, the exomes secreted by variant B cells were characterized by the protein content, electronic microscopy, and cell internalization assays. Critically, exosomes purified from LDL-treated variant B cell promoted cell proliferation, migration, and an increment in lactate concentration. Our results suggest that an autocrine phenomenon induced by exosomes in chemoresistant cells may induce modifications on signaling mechanisms of the p53/Mdm2 axis and activation of p70 ribosomal protein kinase S6. Moreover, the specific down-regulated profile of chaperones Hsp90 and Hsp70 secretion inside the exosomes of the chemoresistant variant could be associated with this phenomenon. Therefore, autocrine activation mediated by exosomes and the effect of LDL internalization may influence changes in exosome chaperone content and modulate proliferative signaling pathways, increasing the aggressiveness of MDA-MB-231 chemoresistant cells.

Acupuncture is a feasible alternative to procedural sedation for shoulder reduction in the emergency department.

Treating shoulder dislocations is common in the emergency department and often requires procedural sedation. The use of acupuncture for treatment of chronic pain has been shown to be successful in various outpatient settings, and some EDs have recently incorporated acupuncture as an analgesia adjunct for chronic painful conditions to avoid opioid therapy. Limited data describe acupuncture to facilitate ED procedures. Here we present two cases of acute shoulder dislocation that were successfully treated with acupuncture as an alternative to parenteral pharmacologic procedural sedation. A 50 year old male sustained an anterior shoulder dislocation after an altercation, and a 59 year old female sustained an anterior dislocation after a fall. Instead of using conventional pharmacologic sedation and analgesia during shoulder reduction, both were treated with acupuncture in the ED. Reduction in both cases was rapid, safe, and avoided use of any parenteral medications, procedural sedation monitoring, or prolonged nurse observation. Using acupuncture as alternative to opioids for ED procedures deserves future study for orthopedic and other common ED procedures.

Cell proliferation and glial cell marker expression in the wall of the third ventricle in the tuberal region of the male mouse hypothalamus during postnatal development.

The third ventricle (3 V) wall of the tuberal hypothalamus is composed of two types of cells; specialized ependymoglial cells called tanycytes located ventrally and ependymocytes dorsally, which control the exchanges between the cerebrospinal fluid and the hypothalamic parenchyma. By regulating the dialogue between the brain and the periphery, tanycytes are now recognized as central players in the control of major hypothalamic functions such as energy metabolism and reproduction. While our knowledge of the biology of adult tanycytes is progressing rapidly, our understanding of their development remains very incomplete. To gain insight into the postnatal maturation of the 3 V ependymal lining, we conducted a comprehensive immunofluorescent study of the mouse tuberal region at four postnatal ages (postnatal day (P) 0, P4, P10, and P20). We analyzed the expression profile of a panel of tanycyte and ependymocyte markers (vimentin, S100, connexin-43 [Cx43], and glial fibrillary acidic protein [GFAP]) and characterized cell proliferation in the 3 V wall using the thymidine analog bromodeoxyuridine. Our results show that most changes in marker expression occur between P4 and P10, with a switch from a 3 V mostly lined by radial cells to the emergence of a tanycytic domain ventrally and an ependymocytic domain dorsally, a drop in cell proliferation and increased expression of S100, Cx43, and GFAP that acquire a mature profile at P20. Our study thus identifies the transition between the first and the second postnatal week as a critical time window for the postnatal maturation of the 3 V wall ependymal lining.

[The specificities of the interventions of physiotherapists in intensive care]. / Les spécificités des interventions des masseurs-kinésithérapeutes en réanimation.

The intervention of physiotherapists in the intensive care unit allows the optimisation of the care project through the assessment and management of the motor, respiratory and swallowing functions of patients. If COVID-19 has only slightly modified the practice of these professionals, the impact of the pandemic on intensive care units has reinforced the added value of their care.

GnRH neurons recruit astrocytes in infancy to facilitate network integration and sexual maturation.

Neurons that produce gonadotropin-releasing hormone (GnRH), which control fertility, complete their nose-to-brain migration by birth. However, their function depends on integration within a complex neuroglial network during postnatal development. Here, we show that rodent GnRH neurons use a prostaglandin D2 receptor DP1 signaling mechanism during infancy to recruit newborn astrocytes that 'escort' them into adulthood, and that the impairment of postnatal hypothalamic gliogenesis markedly alters sexual maturation by preventing this recruitment, a process mimicked by the endocrine disruptor bisphenol A. Inhibition of DP1 signaling in the infantile preoptic region, where GnRH cell bodies reside, disrupts the correct wiring and firing of GnRH neurons, alters minipuberty or the first activation of the hypothalamic-pituitary-gonadal axis during infancy, and delays the timely acquisition of reproductive capacity. These findings uncover a previously unknown neuron-to-neural-progenitor communication pathway and demonstrate that postnatal astrogenesis is a basic component of a complex set of mechanisms used by the neuroendocrine brain to control sexual maturation.

Projection of E-Learning in Higher Education: A Study of Its Scientific Production in Web of Science.

E-learning is conceived as a purely virtual training approach. Different learning styles have been proliferated in recent years, especially now, due to the impact of COVID-19 in the educational field. The aim of this study is to discover the evolution of e-learning in higher education (ELHI) in scientific literature indexed on the Web of Science. Co-word analysis and bibliometric analysis was performed. A total matrix of 1261 documents was analyzed through SciMAT software. The results revealed that studies on ELHI are written in English and presented by conference papers. The main source of publication for the conferences is EDULEARN proceedings, while the journal source is Procedia-Social and Behavioral Sciences. Spain is the country with the highest volume of production. It is concluded that research on ELHI use does not have an established line of research, due to its recent creation and the lack of related research. The bibliometric analysis specifies that the research is oriented towards knowing the level of acceptance and application of the pedagogical method in the teaching and learning processes.

Adaptation and Validation of the Motivated Strategies for Learning Questionnaire for Spanish Adolescents.

This work adapts and validates the scale of the motivated strategies for learning questionnaire (MSLQ), which is used to measure motivation. For this, an instrumental design was carried out with the purpose of analyzing the psychometric properties of the instrument. The sample consisted of 307 participants enrolled in compulsory secondary education. Reliability with fit indices were good in model B (proposed) with composite reliability, global reliability index, and Cronbach's alpha. The original model (A) presented small problems that had to be adjusted when carrying out the translation. We concluded that adaptation and subsequent validation of the MSLQ instrument into a Spanish context was positive. In this sense, adequate adjustment rates have been achieved. However, in its contextual adequacy, the need arises to modify the presentation of the items alluding to intrinsic motivation due to the difficulty of measuring such a construct. Among the implications reached in this study is the possibility of having a validated instrument for the Spanish adolescent context to measure motivation on educational aspects. Furthermore, this tool can serve as the basis for the design of other instruments that measure this construct in other age ranges.

Spanish Adaptation and Validation of the Teaching and Learning Experiences Questionnaire.

Training processes are mainly based on the pedagogical methods applied by teachers. In many cases, these pedagogical methods are adapted to the social, economic, and cultural environment of the students themselves. In this study, we used a psychometric analysis based on the analysis of structural equations to detect the psychometric properties through classical goodness-of-fit indices. The objective of this study was to translate, adapt, and validate the instrument called the Teaching and Learning Experiences Questionnaire (ETLQ) for the population of Spanish adolescents in secondary education. The rrecommendations in the literature were followed for its translation and adaptation into Spanish. The results indicate that, after translation and adaptation, the model remained in 11 factors with acceptable goodness-of-fit indices. We conclude that the process of translation, adaptation, and validation of the ETLQ has produced a valid and reliable tool due to the psychometric findings revealed in the present work.

Gamification and flipped learning and their influence on aspects related to the teaching-learning process.

Nowadays, education is going through a moment of methodological transformation. Two of the active methodologies with excellent projection within the educational field are gamification and flipped learning. This study analyzed the methodological contrast between gamification and flipped learning in the subject of Physical Education in three different educational stages to determine the most influential methodology in the training process. Research design was a quasi-experimental research with a sample of 356 students in Spain. Data collection took place with a questionnaire. The results show that gamification as a teaching and learning methodology is better valued at an early stage, while the more aged participants better value the flipped learning methodology. Both methodologies have shown great potential in the development of educational processes in Physical Education. Gamification indeed seems to have positive effects on students from the lower stages. On the other hand, flipped learning produces positive effects on the group stages, pre-university students.

Surfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum.

Levels of intestinal toll-like receptor 4 (TLR4) impact inflammation in the neonatal gastrointestinal tract. While surfactant protein A (SP-A) is known to regulate TLR4 in the lung, it also reduces intestinal damage, TLR4 and inflammation in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats. We hypothesized that SP-A-deficient (SP-A-/-) mice have increased ileal TLR4 and inflammatory cytokine levels compared to wild type mice, impacting intestinal physiology. We found that ileal TLR4 and proinflammatory cytokine levels were significantly higher in infant SP-A-/- mice compared to wild type mice. Gavage of neonatal SP-A-/- mice with purified SP-A reduced ileal TLR4 protein levels. SP-A reduced expression of TLR4 and proinflammatory cytokines in normal human intestinal epithelial cells (FHs74int), suggesting a direct effect. However, incubation of gastrointestinal cell lines with proteasome inhibitors did not abrogate the effect of SP-A on TLR4 protein levels, suggesting that proteasomal degradation is not involved. In a mouse model of experimental NEC, SP-A-/- mice were more susceptible to intestinal stress resembling NEC, while gavage with SP-A significantly decreased ileal damage, TLR4 and proinflammatory cytokine mRNA levels. Our data suggests that SP-A has an extrapulmonary role in the intestinal health of neonatal mice by modulating TLR4 and proinflammatory cytokines mRNA expression in intestinal epithelium.

Social axioms on high school students in the North African context: Validation and fit of the SAS-II.

Social axioms or general social beliefs represent people's cognitive map of their social world acquired through social experiences. Empirical research has related the central constructs in the study of psychology and social axioms, establishing a broad nomological network in various cultural settings. This paper studies the validity of the Social Axioms Survey II (SAS-II) short form, Spanish version, on the individual level in Melilla as North Africa´s borderland. Participants were 410 high school students from 14 to 18 years of age. The reliability analysis, the discriminant validity analysis, and the confirmatory factor analysis through the structural model equation, showed similar results to previous studies in other contexts and allowing the use of the survey in Melilla. In addition it is presented a fitted model that improves the psychometric results showing significant differences with the initial model. The confirmatory multi-group analysis of the fitted model shows measurement invariance across educational centers, allowing new research possibilities in the cultural context of Melilla.

Effects on Personal Factors Through Flipped Learning and Gamification as Combined Methodologies in Secondary Education.

PURPOSE: This study aims to analyze the effects of a flipped and gamified program on the autonomy, competence, relation with others, satisfaction/enjoyment, intrinsic and extrinsic motivation, and boredom of students of Physical Education. METHOD: The study used a control group and an experimental group to compare pretest and posttest data in both of them. Instruments used were the Basic Psychological Needs in Exercise Scale, Sport Motivation Scale, and Sport Satisfaction Instrument, all of them validated in academic literature. RESULTS: On one hand, data indicated that autonomy has been increased with the application of these teaching methodologies. On the other hand, students' satisfaction, enjoyment, and intrinsic motivation have improved based on the interaction with gamification and flipped learning. Finally, with all dimensions, it seems that academic performance has been improved, although not in a significative way. DISCUSSION/CONCLUSION: Results of the study provide to educational researchers valuable information for a better understanding of how flipped learning and gamification influence personal performance of Physical Education students.

Evaluating Activation and Absence of Negative Effect: Gamification and Escape Rooms for Learning.

Innovation has allowed for and developed new ways of teaching and learning. Gamification is among the new training methodologies, which is a didactic approach based on the game structure with an attractive component for students. Within gamification, flipped learning and problem-based learning, escape rooms can be found as a technical aspect, which is focused on providing enigmas and tracks for the various educational content that students have assimilated through learning based on problem solving. The aim of this study is to identify how the use of gamification with the use of educational escape rooms affects activation and absence of a negative effect on students. 61 Master students of the Autonomous City of Ceuta participated in this case study. They were divided into three study groups (1 control group; 2 experimental groups) that followed different formative actions (control group-traditional; experimental groups-escape rooms). To achieve the objectives, a mixed research design based on quantitative and qualitative techniques was followed. The instrument used for data collection was the GAMEX (Gameful Experience Scale). The results reveal that the students who had taken a gamified formative action through escape rooms obtained better assessment results in the indicators concerning motivation, teamwork, commitment, activation, and absence of a negative effect on the learning process than those with the traditional methodology.

Scientific Mapping of Gamification in Web of Science.

Education is a constantly changing field. The new teaching processes are developed today and all teachers should be prepared. Gamification is one of the methodologies with the greatest impact on the learning process. The objective of the study is to analyze the relevance and progression that the concepts "gamification" and "learning" have acquired in the scientific literature of Web of Science. This research has been based on a bibliometric methodology. A classic bibliometric and thematic analyses have been carried out. A 1230 document matrix analysis has been selected. For descriptive bibliometrics, the Bibliometrix library is used, while Scimat is used for the thematic analysis. Both tools are widely used in this type of study. Results indicate that growth on the study of these topics is booming. There are also authors who accumulate most of the documents, such as Martí Parreño. English is positioned as the predominant language. The topics studied have evolved from how classic games affect learning to the study of video games and their impact on performance. It is concluded that these types of studies are still relevant and with a great future prospect. Furthermore, research focuses especially on video games, on the effects of technology on learning and on the study of flipped learning experiences.

[Analysis of nursing student prejudices towards the migrant population]. / Análisis de los prejuicios del alumnado de enfermería hacia la población migrante.

OBJECTIVE: To determine whether nursing students have subtle or blatant prejudices towards migrants. METHOD: A descriptive ex post facto study was conducted. The sample consisted of 282 students and the study variables were sex, cultural origin, age, year, and contact with migrants. The Subtle and Blatant Prejudice Scale was used. Descriptive and inferential analyses were performed. RESULTS: There were significant differences in the culture variable, with students of Berber origin and of Muslim faith showing less prejudice than those of European origin and of Christian faith. Fourth-year students had the most blatant prejudices. According to the variable contact with migrants, it is the students who have not had contact with this group who have the greatest blatant prejudices. CONCLUSION: Nursing students have more subtle prejudices rather than blatant prejudices towards the migrant population.

Enfermería Transcultural. Formación de los futuros profesionales de Enfermería en España / Transcultural Nursing. Training of future Nursing professionals in Spain

Objetivo principal: conocer las Facultades de Enfermería que en España se imparte la asignatura de Enfermería Transcultural o similar, así como saber si son asignaturas obligatorias u optativas. Metodología: Revisión de los planes de estudios de las Universidades españolas donde se imparte la titulación de Enfermería. Resultados principales: De las Universidades examinadas, el 63% de las titulaciones de Enfermería ofrece formación específica en Enfermería Transcultural. Conclusión principal: No existe un compromiso firme desde el ámbito académico en Enfermería en la formación transcultural de los futuros profesionales de enfermería

Objective: Know what Faculties of Nursing in Spain are teaching Transcultural Nursing or similar subjetcs, as well as knowing if they are compulsory or optional subjects. Methods: Review of the curricula of the Spanish Universities where the Nursing degree is taught. Results: Results obtained show that only a 63% of Nursing degrees offers specific training in Transcultural Nursing. Conclusions: There is no firm commitment in Nursing degrees about cross-cultural training of future nursing professionals

Reducing the Flexibility of Type†II Dehydroquinase for Inhibition: A Fragment-Based Approach and Molecular Dynamics Study.

A multidisciplinary approach was used to identify and optimize a quinazolinedione-based ligand that would decrease the flexibility of the substrate-covering loop (catalytic loop) of the type II dehydroquinase from Helicobacter pylori. This enzyme, which is essential for the survival of this bacterium, is involved in the biosynthesis of aromatic amino acids. A computer-aided fragment-based protocol (ALTA) was first used to identify the aromatic fragments able to block the interface pocket that separates two neighboring enzyme subunits and is located at the active site entrance. Chemical modification of its non-aromatic moiety through an olefin cross-metathesis and Seebach's self-reproduction of chirality synthetic principle allowed the development of a quinazolinedione derivative that disables the catalytic loop plasticity, which is essential for the enzyme's catalytic cycle. Molecular dynamics simulations revealed that the ligand would force the catalytic loop into an inappropriate arrangement for catalysis by strong interactions with the catalytic tyrosine and by expelling the essential arginine out of the active site.

Neurophysiological Evidence for a Cortical Contribution to the Wakefulness-Related Drive to Breathe Explaining Hypocapnia-Resistant Ventilation in Humans.

Spontaneous ventilation in mammals is driven by automatic brainstem networks that generate the respiratory rhythm and increase ventilation in the presence of increased carbon dioxide production. Hypocapnia decreases the drive to breathe and induces apnea. In humans, this occurs during sleep but not during wakefulness. We hypothesized that hypocapnic breathing would be associated with respiratory-related cortical activity similar to that observed during volitional breathing, inspiratory constraints, or in patients with defective automatic breathing (preinspiratory potentials). Nineteen healthy subjects were studied under passive (mechanical ventilation, n = 10) or active (voluntary hyperventilation, n = 9) profound hypocapnia. Ventilatory and electroencephalographic recordings were performed during voluntary sniff maneuvers, normocapnic breathing, hypocapnia, and after return to normocapnia. EEG recordings were analyzed with respect to the ventilatory flow signal to detect preinspiratory potentials in frontocentral electrodes and to construct time-frequency maps. After passive hyperventilation, hypocapnia was associated with apnea in 3 cases and ventilation persisted in 7 cases (3 and 6 after active hyperventilation, respectively). No respiratory-related EEG activity was observed in subjects with hypocapnia-related apneas. In contrast, preinspiratory potentials were present at vertex recording sites in 12 of the remaining 13 subjects (p < 0.001). This was corroborated by time-frequency maps. This study provides direct evidence of a cortical substrate to hypocapnic breathing in awake humans and fuels the notion of corticosubcortical cooperation to preserve human ventilation in a variety of situations. Of note, maintaining ventilatory activity at low carbon dioxide levels is among the prerequisites to speech production insofar as speech often induces hypocapnia. SIGNIFICANCE STATEMENT: Human ventilatory activity persists, during wakefulness, even when hypocapnia makes it unnecessary. This peculiarity of human breathing control is important to speech and speech-breathing insofar as speech induces hypocapnia. This study evidences a specific respiratory-related cortical activity. This suggests that human hypocapnic breathing is driven, at least in part, by cortical mechanisms similar to those involved in volitional breathing, in breathing against mechanical constraints or with weak inspiratory muscle, and in patients with defective medullary breathing pattern generators. This fuels the notion that the human ventilatory drive during wakefulness often results from a corticosubcortical cooperation, and opens new avenues to study certain ventilatory and speech disorders.