Using Virtual Reality to Study Spatial Mapping and Threat Learning.

Using spatial mapping processes to learn about threat and safety in an environment is crucial for survival. Research using conditioning paradigms has explored the effects of state (transient arousal) and trait anxiety (anxiety as an aspect of personality) on threat learning and acquisition. However, results are mixed, and little is known regarding why some individuals do not learn to discriminate between threat and safety during contextual conditioning. We used a virtual reality (VR) contextual threat conditioning paradigm to elucidate the effects of state and trait anxiety on contextual threat learning. 70 healthy participants (46 female) navigated and "picked" flowers in a VR environment. Flowers picked in the dangerous zone (half of the environment) were paired with an electric shock (or "bee sting") to the hand; flowers picked in the safe zone were never paired with a shock. Participants also collected and returned neutral objects as a measure of spatial memory. Galvanic skin response (GSR) was measured throughout the task and anxiety was assessed via the State Trait Anxiety Inventory (STAI). Participants were categorized as learners if they correctly identified the two zones after the task. Non-learners, compared to learners, performed significantly worse during the spatial memory task and demonstrated significantly higher state anxiety scores and GSR levels throughout the task. Learners showed higher skin conductance response (SCR) in the dangerous zone compared to the safe zone while non-learners showed no SCR differences between zones. These results indicate that state anxiety may impair spatial mapping, disrupting contextual threat learning.

Flow Cytometry of Synaptoneurosomes (FCS) Reveals Increased Ribosomal S6 and Calcineurin Proteins in Activated Medial Prefrontal Cortex to Nucleus Accumbens Synapses.

Learning and behavior activate cue-specific patterns of sparsely distributed cells and synapses called ensembles that undergo memory-encoding engram alterations. While Fos is often used to label selectively activated cell bodies and identify neuronal ensembles, there is no comparable endogenous marker to label activated synapses and identify synaptic ensembles. For the purpose of identifying candidate synaptic activity markers, we optimized a flow cytometry of synaptoneurosome (FCS) procedure for assessing protein alterations in activated synapses from male and female rats. After injecting yellow fluorescent protein (YFP)-expressing adeno-associated virus into medial prefrontal cortex (mPFC) to label terminals in nucleus accumbens (NAc) of rats, we injected 20 mg/kg cocaine in a novel context (cocaine+novelty) to activate synapses, and prepared NAc synaptoneurosomes 0-60 min following injections. For FCS, we used commercially available antibodies to label presynaptic and postsynaptic markers synaptophysin and PSD-95 as well as candidate markers of synaptic activity [activity-regulated cytoskeleton protein (Arc), CaMKII and phospho-CaMKII, ribosomal protein S6 (S6) and phospho-S6, and calcineurin and phospho-calcineurin] in YFP-labeled synaptoneurosomes. Cocaine+novelty increased the percentage of S6-positive synaptoneurosomes at 5-60 min and calcineurin-positive synaptoneurosomes at 5-10 min. Electron microscopy verified that S6 and calcineurin levels in synaptoneurosomes were increased 10 min after cocaine+novelty. Pretreatment with the anesthetic chloral hydrate blocked cocaine+novelty-induced S6 and calcineurin increases in synaptoneurosomes, and novel context exposure alone (without cocaine) increased S6, both of which indicate that these increases were due to neural activity per se. Overall, FCS can be used to study protein alterations in activated synapses coming from specifically labeled mPFC projections to NAc.SIGNIFICANCE STATEMENT Memories are formed during learning and are stored in the brain by long-lasting molecular and cellular alterations called engrams formed within specific patterns of cue-activated neurons called neuronal ensembles. While Fos has been used to identify activated ensemble neurons and the engrams within them, we have not had a similar marker for activated synapses that can be used to identify synaptic engrams. Here we developed a procedure for high-throughput in-line analysis of flow cytometry of synaptoneurosome (FCS) and found that ribosomal S6 protein and calcineurin were increased in activated mPFC-NAc synapses. FCS can be used to study protein alterations in activated synapses within specifically labeled circuits.

Intervention for Intraoperative Teaching in Anesthesiology Using Weekly Keyword Program: Development and Usability Study.

BACKGROUND: Learning in the operating room (OR) for residents in anesthesiology is difficult but essential for successful resident education. Numerous approaches have been attempted in the past to varying degrees of success, with efficacy often judged afterward using surveys distributed to participants. The OR presents a particularly complex set of challenges for academic faculty due to the pressures required by concurrent patient care, production pressures, and a noisy environment. Often, educational reviews in ORs are personnel specific, and instruction may or may not take place in this setting, as it is left to the discretion of the parties without regular direction. OBJECTIVE: This study aims to determine if a structured intraoperative keyword training program could be used to implement a curriculum to improve teaching in the OR and to facilitate impactful discussion between residents and faculty. A structured curriculum was chosen to allow for the standardization of the educational material to be studied and reviewed by faculty and trainees. Given the reality that educational reviews in the OR tend to be personnel specific and are often focused on the clinical cases of the day, this initiative sought to increase both the time and efficiency of learning interactions between learners and teachers in the stressful environment of the OR. METHODS: The American Board of Anesthesiology keywords from the Open Anesthesia website were used to construct a weekly intraoperative didactic curriculum, which was distributed by email to all residents and faculty. A weekly worksheet from this curriculum included 5 keywords with associated questions for discussion. The residents and faculty were instructed to complete these questions on a weekly basis. After 2 years, an electronic survey was distributed to the residents to evaluate the efficacy of the keyword program. RESULTS: A total of 19 teaching descriptors were polled for participants prior to and following the use of the intraoperative keyword program to assess the efficacy of the structured curriculum. The survey results showed no improvement in intraoperative teaching based on respondent perception, despite a slight improvement in teaching time, though this was statistically insignificant. The respondents reported some favorable aspects of the program, including the use of a set curriculum, suggesting that greater structure may be beneficial to facilitate more effective intraoperative teaching in anesthesiology. CONCLUSIONS: Although learning is difficult in the OR for residents, the use of a formalized didactic curriculum, centered on daily keywords, does not appear to be a useful solution for residents and faculty. Further efforts are required to improve intraoperative teaching, which is well known to be a difficult endeavor for both teachers and trainees. A structured curriculum may be used to augment other educational modalities to improve the overall intraoperative teaching for anesthesia residents.

Effect of Selective Lesions of Nucleus Accumbens µ-Opioid Receptor-Expressing Cells on Heroin Self-Administration in Male and Female Rats: A Study with Novel Oprm1-Cre Knock-in Rats.

The brain µ-opioid receptor (MOR) is critical for the analgesic, rewarding, and addictive effects of opioid drugs. However, in rat models of opioid-related behaviors, the circuit mechanisms of MOR-expressing cells are less known because of a lack of genetic tools to selectively manipulate them. We introduce a CRISPR-based Oprm1-Cre knock-in transgenic rat that provides cell type-specific genetic access to MOR-expressing cells. After performing anatomic and behavioral validation experiments, we used the Oprm1-Cre knock-in rats to study the involvement of NAc MOR-expressing cells in heroin self-administration in male and female rats. Using RNAscope, autoradiography, and FISH chain reaction (HCR-FISH), we found no differences in Oprm1 expression in NAc, dorsal striatum, and dorsal hippocampus, or MOR receptor density (except dorsal striatum) or function between Oprm1-Cre knock-in rats and wildtype littermates. HCR-FISH assay showed that iCre is highly coexpressed with Oprm1 (95%-98%). There were no genotype differences in pain responses, morphine analgesia and tolerance, heroin self-administration, and relapse-related behaviors. We used the Cre-dependent vector AAV1-EF1a-Flex-taCasp3-TEVP to lesion NAc MOR-expressing cells. We found that the lesions decreased acquisition of heroin self-administration in male Oprm1-Cre rats and had a stronger inhibitory effect on the effort to self-administer heroin in female Oprm1-Cre rats. The validation of an Oprm1-Cre knock-in rat enables new strategies for understanding the role of MOR-expressing cells in rat models of opioid addiction, pain-related behaviors, and other opioid-mediated functions. Our initial mechanistic study indicates that lesioning NAc MOR-expressing cells had different effects on heroin self-administration in male and female rats.SIGNIFICANCE STATEMENT The brain µ-opioid receptor (MOR) is critical for the analgesic, rewarding, and addictive effects of opioid drugs. However, in rat models of opioid-related behaviors, the circuit mechanisms of MOR-expressing cells are less known because of a lack of genetic tools to selectively manipulate them. We introduce a CRISPR-based Oprm1-Cre knock-in transgenic rat that provides cell type-specific genetic access to brain MOR-expressing cells. After performing anatomical and behavioral validation experiments, we used the Oprm1-Cre knock-in rats to show that lesioning NAc MOR-expressing cells had different effects on heroin self-administration in males and females. The new Oprm1-Cre rats can be used to study the role of brain MOR-expressing cells in animal models of opioid addiction, pain-related behaviors, and other opioid-mediated functions.

Outcomes and Disposition of Patients After Case Cancellation on Day of Surgery for Reasons Attributed to Medical or Anesthetic Care: A Retrospective Cohort Analysis.

BACKGROUND: Many day-of-surgery cancellations are avoidable, and different strategies are used to prevent these costly adverse events. Despite these past analyses and evaluations of positive interventions, studies have not examined the final disposition of patients whose cases were canceled in this late manner. This study sought to determine whether surgical procedures canceled for medical or anesthetic reasons were ultimately rescheduled, and the time elapsed between cancellation and completion. In addition, the resolution of the underlying issue leading to cancellation was examined. METHODS: Two years of surgical case data were reviewed in the electronic health record to isolate all procedures canceled on the intended operative date. These cases were then filtered by the documented reason for cancellation into 2 categories: 1 for cases related to medical or anesthetic care and 1 for unrelated cases. Medical- or anesthetic-related cases were further categorized to better elucidate the underlying reason for cancellation. Cases were then traced to determine if and when the procedure was ultimately completed. If a case was rescheduled, the record was reviewed to determine whether the underlying reason for cancellation was resolved. RESULTS: A total of 4472 cases were canceled in the study period with only 20% associated with medical or anesthetic causes. Of these, 72% were rescheduled and 83% of all rescheduled cases resolved the underlying issue before the rescheduled procedure. Nearly half of all cases (47.8%) canceled on the day of surgery for reasons linked to medical and/or anesthetic care were due to acute conditions. CONCLUSIONS: Nearly a fifth of cases that are canceled on the date of surgery are never rescheduled and, if they are rescheduled, the delay can be substantial. Although the majority of patients whose procedure are canceled for reasons related to medical or anesthetic care have resolved the underlying issue that led to initial postponement, a significant portion of patients have no change in their status before the ultimate completion of their surgical procedure.

SMART: An Open-Source Extension of WholeBrain for Intact Mouse Brain Registration and Segmentation.

Mapping immediate early gene (IEG) expression across intact mouse brains allows for unbiased identification of brain-wide activity patterns underlying complex behaviors. Accurate registration of sample brains to a common anatomic reference is critical for precise assignment of IEG-positive ("active") neurons to known brain regions of interest (ROIs). While existing automated voxel-based registration methods provide a high-throughput solution, they require substantial computing power, can be difficult to implement and fail when brains are damaged or only partially imaged. Additionally, it is challenging to cross-validate these approaches or compare them to any preexisting literature based on serial coronal sectioning. Here, we present the open-source R package SMART (Semi-Manual Alignment to Reference Templates) that extends the WholeBrain R package framework to automated segmentation and semi-automated registration of intact mouse brain light-sheet fluorescence microscopy (LSFM) datasets. The SMART package was created for novice programmers and introduces a streamlined pipeline for aligning, registering, and segmenting LSFM volumetric datasets across the anterior-posterior (AP) axis, using a simple "choice game" and interactive menus. SMART provides the flexibility to register whole brains, partial brains or discrete user-chosen images, and is fully compatible with traditional sectioned coronal slice-based analyses. We demonstrate SMART's core functions using example datasets and provide step-by-step video tutorials for installation and implementation of the package. We also present a modified iDISCO+ tissue clearing procedure for uniform immunohistochemical labeling of the activity marker Fos across intact mouse brains. The SMART pipeline, in conjunction with the modified iDISCO+ Fos procedure, is ideally suited for examination and orthogonal cross-validation of brain-wide neuronal activation datasets.

Medial prefrontal cortex and anteromedial thalamus interaction regulates goal-directed behavior and dopaminergic neuron activity.

The prefrontal cortex is involved in goal-directed behavior. Here, we investigate circuits of the PFC regulating motivation, reinforcement, and its relationship to dopamine neuron activity. Stimulation of medial PFC (mPFC) neurons in mice activated many downstream regions, as shown by fMRI. Axonal terminal stimulation of mPFC neurons in downstream regions, including the anteromedial thalamic nucleus (AM), reinforced behavior and activated midbrain dopaminergic neurons. The stimulation of AM neurons projecting to the mPFC also reinforced behavior and activated dopamine neurons, and mPFC and AM showed a positive-feedback loop organization. We also found using fMRI in human participants watching reinforcing video clips that there is reciprocal excitatory functional connectivity, as well as co-activation of the two regions. Our results suggest that this cortico-thalamic loop regulates motivation, reinforcement, and dopaminergic neuron activity.

Morphine and Fentanyl Repeated Administration Induces Different Levels of NLRP3-Dependent Pyroptosis in the Dorsal Raphe Nucleus of Male Rats via Cell-Specific Activation of TLR4 and Opioid Receptors.

Morphine promotes neuroinflammation after NOD-like receptor protein 3 (NLRP3) oligomerization in glial cells, but the capacity of other opioids to induce neuroinflammation and its relationship to the development of analgesic tolerance is unknown. We studied the effects of morphine and fentanyl on NLRP3 inflammasome activation in glial and neuronal cells in the dorsal raphe nucleus (DRN), a region involved in pain regulation. Male Wistar rats received i.p. injections of morphine (10 mg/kg) or fentanyl (0.1 mg/kg) 3 × daily for 7 days and were tested for nociception. Two hours after the last (19th) administration, we analyzed NLRP3 oligomerization, caspase-1 activation and gasdermin D-N (GSDMD-N) expression in microglia (CD11b positive cells), astrocytes (GFAP-positive cells) and neurons (NeuN-positive cells). Tolerance developed to both opioids, but only fentanyl produced hyperalgesia. Morphine and fentanyl activated NLRP3 inflammasome in astrocytes and serotonergic (TPH-2-positive) neurons, but fentanyl effects were more pronounced. Both opioids increased GFAP and CD11b immunoreactivity, caspase-1 and GSDMD activation, indicating pyroptotic cell death. The opioid receptor antagonist (-)-naloxone, but not the TLR4 receptor antagonist (+)-naloxone, prevented microglia activation and NLRP3 oligomerization. Only (+)-naloxone prevented astrocytes' activation. The anti-inflammatory agent minocycline and the NLRP3 inhibitor MCC950 delayed tolerance to morphine and fentanyl antinociception and prevented fentanyl-induced hyperalgesia. MCC950 also prevented opioid-induced NLRP3 oligomerization. In conclusion, morphine and fentanyl differentially induce cell-specific activation of NLRP3 inflammasome and pyroptosis in the DRN through TLR4 receptors in astrocytes and through opioid receptors in neurons, indicating that neuroinflammation is involved in opioid-induced analgesia and fentanyl-induced hyperalgesia after repeated administrations.

La relación entre la edad, el engagement y la disposición al cambio organizacional / The relationship between age, engagement and disposition to organizational change

Resumen La gestión de recursos humanos como función estratégica en las organizaciones de trabajo constituye en la actualidad una actividad de alta complejidad que implica importantes retos para los líderes de gestión humana a nivel global, debido a los procesos de cambio constante que viven las organizaciones de todo tipo. Estos procesos están dados tanto por exigencias provenientes de las transformaciones del entorno como por los requerimientos internos de ajuste en las organizaciones para mantener su productividad y competitividad en la dinámica de los mercados actuales, condiciones que imprimen serias implicaciones en la gestión del cambio y su relación con el comportamiento, desempeño y compromiso de los trabajadores. El objetivo de esta investigación fue identificar la posible relación entre la edad, el engagement, y la disposición al cambio organizacional, ya que estas variables resultan tener un papel clave en la gestión de recursos humanos en el contexto actual del mundo del trabajo, según se concluye de estudios previos que muestran relaciones entre diferentes tipos de compromiso y procesos de cambio organizacional. La presente investigación se enmarca en la perspectiva de la psicología positiva, un enfoque reciente que busca alejarse del énfasis en lo patológico del comportamiento para centrarse en los aspectos positivos y el potencial del ser humano. Esta perspectiva de la psicología en el campo del estudio del comportamiento organizacional se ha denominado "psicología organizacional positiva". Para lograr los objetivos de identificar la relación entre las variables, se realizó un estudio predictivo, que se orienta fundamentalmente a indagar la relación funcional entre dos o más variables, con un diseño correlacional simple en el que no se utilizan formas de control de variables extrañas que puedan tener influencia en la relación funcional investigada. La muestra estuvo compuesta por 808 personas divididas en dos submuestras (35.5 % colombianos y 65.5 % ecuatorianos), seleccionadas de manera no probabilística accidental. Para la evaluación de las variables se utilizó el autorreporte en la edad, el cuestionario Utrecht Work Engagement Scale (UWES) y el instrumento Disposición al Cambio Organizacional. Los resultados mostraron relaciones significativas entre las variables disposición al cambio organizacional y engagement, tanto a nivel general como en las submuestras. Sin embargo, al indagar sobre el posible papel moderador de la edad entre las otras dos variables, no se encontraron evidencias al respecto. Otros análisis sugieren la posibilidad de un efecto mediado por aspectos culturales que puede incidir en la disposición al cambio. El presente estudio constituye un importante aporte en la comprensión del comportamiento humano en el trabajo en relación con procesos de cambio organizacional, específicamente la asociación de este con variables como el engagement y la edad. Sin embargo, sucesos recientes como la situación mundial derivada de la pandemia por el virus SARSCOV2 y su impacto en las dinámicas de trabajo sugieren la necesidad de avanzar en estudios complementarios al realizado por los autores y que se presenta en este artículo, puesto que las actividades laborales han migrado para muchas personas del contexto de la empresa al contexto del hogar, lo que pone en escena otras variables que podrían incidir en la relación aquí indagada.

Abstract Human resource management as a strategic function in work organizations is currently a highly complex activity that implies significant challenges for human management leaders at a global level, due to the processes of constant change that all kind of organizations must experience, due to demands arising from the transformations of the environment and the internal requirements of adjustment in organizations to maintain their productivity and competitiveness in the dynamics of current markets, conditions that have serious implications in the management of change and its relationship with behavior , performance and commitment of the workers.. In this context, the human resources area has the important task of contributing to the management of human talent to achieve high levels of commitment from people in organizations and facilitate change processes, if organizational leaders want to achieve strategic objectives in a much more effective way. To achieve this, it is necessary to identify key variables that affect human behavior in work contexts and understand the possible relationships between these variables. The main objective of this research was to identify the relationship between age, engagement, and disposition to organizational change since these variables turn out to have a key role in human resource management in the current context of the world of work. The present investigation is framed in the perspective of positive psychology, a recent approach that seeks to move away from the emphasis on the pathological behavior to focus on the positive aspects and potential of the human being. This is the perspective of psychology in the field of the study of organizational behavior has been called positive organizational psychology. To achieve the objectives of identifying the relationship between the variables, a predictive study with a simple correlational design was performed. This kind of study is mainly oriented to investigate the functional relationship between two or more variables in which no forms of control of strange variables are used. The sample was made up of 808 people divided into two sub-samples (35.5 % Colombian and 65.5 % Ecuadorian), selected in an accidental non-probabilistic way; The self-report on age, the Utrecht Work Engagement Scale (UWES) questionnaire and the instrument Disposition to organizational change were used to evaluate the variables. The results showed significant relationships between the variables disposition to organizational change and engagement, both in general and in the subsamples; however, when investigating the possible role of age in moderating the other two variables, no evidence was found in this regard. Other analyzes suggest the possibility of an effect mediated by cultural aspects that may affect the readiness to change. However, recent events such as the world situation derived from the SARSCOV2 virus pandemic and its impact on work dynamics, suggest the need to advance in complementary studies to the one carried out by the authors and presented in this article, since the Work activities have migrated for many people from the context of the company to the context of the home, which highlights other variables that could affect the relationship investigated here.

Relapse-Associated Transient Synaptic Potentiation Requires Integrin-Mediated Activation of Focal Adhesion Kinase and Cofilin in D1-Expressing Neurons.

Relapse to drug use can be initiated by drug-associated cues. The intensity of cue-induced drug seeking in rodent models correlates with the induction of transient synaptic potentiation (t-SP) at glutamatergic synapses in the nucleus accumbens core (NAcore). Matrix metalloproteinases (MMPs) are inducible endopeptidases that degrade extracellular matrix (ECM) proteins, and reveal tripeptide Arginine-Glycine-Aspartate (RGD) domains that bind and signal through integrins. Integrins are heterodimeric receptors composed of αß subunits, and a primary signaling kinase is focal adhesion kinase (FAK). We previously showed that MMP activation is necessary for and potentiates cued reinstatement of cocaine seeking, and MMP-induced catalysis stimulates ß3-integrins to induce t-SP. Here, we determined whether ß3-integrin signaling through FAK and cofilin (actin depolymerization factor) is necessary to promote synaptic growth during t-SP. Using a small molecule inhibitor to prevent FAK activation, we blocked cued-induced cocaine reinstatement and increased spine head diameter (dh). Immunohistochemistry on NAcore labeled spines with ChR2-EYFP virus, showed increased immunoreactivity of phosphorylation of FAK (p-FAK) and p-cofilin in dendrites of reinstated animals compared with extinguished and yoked saline, and the p-FAK and cofilin depended on ß3-integrin signaling. Next, male and female transgenic rats were used to selectively label D1 or D2 neurons with ChR2-mCherry. We found that p-FAK was increased during drug seeking in both D1 and D2-medium spiny neurons (MSNs), but increased p-cofilin was observed only in D1-MSNs. These data indicate that ß3-integrin, FAK and cofilin constitute a signaling pathway downstream of MMP activation that is involved in promoting the transient synaptic enlargement in D1-MSNs induced during reinstated cocaine by drug-paired cues.SIGNIFICANCE STATEMENT Drug-associated cues precipitate relapse, which is correlated with transient synaptic enlargement in the accumbens core. We showed that cocaine cue-induced synaptic enlargement depends on matrix metalloprotease signaling in the extracellular matrix (ECM) through ß3-integrin to activate focal adhesion kinase (FAK) and phosphorylate the actin binding protein cofilin. The nucleus accumbens core (NAcore) contains two predominate neuronal subtypes selectively expressing either D1-dopamine or D2-dopamine receptors. We used transgenic rats to study each cell type and found that cue-induced signaling through cofilin phosphorylation occurred only in D1-expressing neurons. Thus, cocaine-paired cues initiate cocaine reinstatement and synaptic enlargement through a signaling cascade selectively in D1-expressing neurons requiring ECM stimulation of ß3-integrin-mediated phosphorylation of FAK (p-FAK) and cofilin.

Aspectos de la cultura organizacional y su relación con la disposición al cambio organizacional / Aspects of organizational culture and its relation to the organizational change disposition

Resumen El objetivo de esta investigación fue determinar la relación entre la cultura organizacional y la disposición al cambio organizacional. Se trata de una investigación empírica que, de acuerdo con el objetivo de investigación, responde a una estrategia asociativa, en un estudio predictivo desarrollado bajo un diseño correlacional simple. La muestra estuvo compuesta por 558 participantes de cuatro entidades de educación superior. Para la evaluación de las variables se emplearon la adaptación para Colombia del OCAI (Organizational Culture Assessment Instrument) y la prueba Disposición al Cambio Organizacional. Los resultados mostraron relaciones significativas entre los factores y los tipos de cultura organizacional con las macro y microdimensiones de la disposición al cambio organizacional. También se encontraron diferencias significativas entre las instituciones en las dimensiones grupal y organizacional de la disposición al cambio, en el factor organizacional y en el tipo de cultura jerárquica. Se evidencia cómo la cultura organizacional se relaciona particularmente con aspectos organizacionales y la comunicación empresarial.

Abstract The objective of this research was to determine the relationship between aspects of organizational culture and the disposition to organizational change. A quantitative, nonexperimental study was carried out under a comparative design; with a sample of 558 participants from four higher education institutions. The instruments used allowed the evaluation of the organizational culture -OCAI- and the willingness to change. The results showed significant relationships between the factors and the types of organizational culture with the macro and micro dimensions of the disposition to organizational change. Significant differences were also found between the institutions in the group and organizational dimensions of the disposition to change; in the organizational factor and the type of hierarchical culture. It is evident how the organizational culture is particularly related to organizational aspects and business communication.

Focal transcranial magnetic stimulation in awake rats: Enhanced glucose uptake in deep cortical layers.

BACKGROUND: Transcranial magnetic stimulation (TMS) is an emerging neuromodulation tool. However, preclinical models of TMS are limited. OBJECTIVE: To develop a method for performing TMS in awake rats and to characterize neuronal response to TMS by mapping glucose uptake following TMS administration. METHODS: A headpost was implanted into rat skull serving as a refence to guide TMS target. Motor threshold measurement was used as the metric to assess the consistency in TMS delivery across animals and across sessions. Using a fluorescent glucose analogue (2-NBDG) as a marker of neuronal activity, we mapped glucose uptake in response to TMS of the rat motor cortex. RESULTS: The average motor threshold (n = 41) was 34.6 ± 6.3 % of maximum stimulator output (MSO). The variability of motor threshold across animals was similar to what has been reported in human studies. Furthermore, there was no significant difference in motor threshold measured across 3 separate days. Enhancement in fluorescent signals were TMS dose (power)-dependent, which centered around the motor cortex, covering an area medial-laterally 2 mm, rostral-caudally 4 mm at 55 % MSO, and 3 mm at 35 % MSO. The count of total cells with significant fluorescent signal was: 107 ± 23 (55 % MSO), 73 ± 11 (35 % MSO) and 42 ± 11 (sham, 5% MSO). CONCLUSIONS: Our method allows for consistent motor threshold assessment for longitudinal studies. Notably, cells with fluorescent signal enhancement were consistently aggregated in deep cortical layers, with minimal enhancement in superficial layers COMPARISONS WITH EXISTING METHOD(S): To our knowledge, this is the first study of focal TMS in awake rodents.

Neuron-Specific Genome Modification in the Adult Rat Brain Using CRISPR-Cas9 Transgenic Rats.

Historically, the rat has been the preferred animal model for behavioral studies. Limitations in genome modification have, however, caused a lag in their use compared to the bevy of available transgenic mice. Here, we have developed several transgenic tools, including viral vectors and transgenic rats, for targeted genome modification in specific adult rat neurons using CRISPR-Cas9 technology. Starting from wild-type rats, knockout of tyrosine hydroxylase was achieved with adeno-associated viral (AAV) vectors expressing Cas9 or guide RNAs (gRNAs). We subsequently created an AAV vector for Cre-dependent gRNA expression as well as three new transgenic rat lines to specifically target CRISPR-Cas9 components to dopaminergic neurons. One rat represents the first knockin rat model made by germline gene targeting in spermatogonial stem cells. The rats described herein serve as a versatile platform for making cell-specific and sequence-specific genome modifications in the adult brain and potentially other Cre-expressing tissues of the rat.

Dorsal Raphe Dual Serotonin-Glutamate Neurons Drive Reward by Establishing Excitatory Synapses on VTA Mesoaccumbens Dopamine Neurons.

Dorsal raphe (DR) serotonin neurons provide a major input to the ventral tegmental area (VTA). Here, we show that DR serotonin transporter (SERT) neurons establish both asymmetric and symmetric synapses on VTA dopamine neurons, but most of these synapses are asymmetric. Moreover, the DR-SERT terminals making asymmetric synapses on VTA dopamine neurons coexpress vesicular glutamate transporter 3 (VGluT3; transporter for accumulation of glutamate for its synaptic release), suggesting the excitatory nature of these synapses. VTA photoactivation of DR-SERT fibers promotes conditioned place preference, elicits excitatory currents on mesoaccumbens dopamine neurons, increases their firing, and evokes dopamine release in nucleus accumbens. These effects are blocked by VTA inactivation of glutamate and serotonin receptors, supporting the idea of glutamate release in VTA from dual DR SERT-VGluT3 inputs. Our findings suggest a path-specific input from DR serotonergic neurons to VTA that promotes reward by the release of glutamate and activation of mesoaccumbens dopamine neurons.

Estrés laboral y contrato psicológico como elementos relaciónales del cambio organizacional / Labor stress and psychological contract as relational elements of organizational change

Resumen El objetivo de este estudio fue identificar la relación entre estrés laboral y contrato psicológico, respecto al cambio organizacional en empleados de cuatro empresas en Bogotá. El estudio se llevó a cabo mediante la aplicación del cuestionario de roles ocupacionales adaptado a la población colombiana por García-Neira, et al., (2012), el inventario de contrato psicológico versión 2 y el de medición de cambio organizacional. Los participantes fueron 100 colaboradores de distintas organizaciones del sector privado. Se realizó un estudio transversal de alcance correlacional corroborado a partir de un análisis de regresión simple. Se evidenció que la variable de cambio organizacional correlaciona con la mayoría de las subvariables de contrato psicológico de manera positiva, y con las de estrés de manera negativa. Finalmente se encontró que el contrato psicológico explica el cambio organizacional en un mayor nivel predictivo que el estrés laboral. Estos resultados constituyen un aporte teórico y empírico para que las organizaciones comprendan cómo abordar los procesos de cambio organizacional.

Abstract The goal of this research was to identify the relationship between work stress and psychological contract in the process of organizational change in employees of four companies in Bogotá. We used the Colombian adaptation of the questionnaire of occupational roles by García - Neira, Piraquive, Salazar, & García (2012), the inventory of psychological contract, version 2 and the organizational change measure. Then, we performed a correlational cross-sectional analysis corroborated with a simple regression analysis. Organizational change was found to positively correlate with most subvariables of psychological contract, and negatively with stress. Finally, psychological contract seemed to explain organizational change at a higher predictive level than work-related stress. These results are a theoretical and empirical contribution that may be used by organizations to understand how to approach organizational change.

Antecedentes históricos, filosóficos y administrativos de la fundación del Instituto Nacional de Higiene de la República Bolivariana de Venezuela / Historical, philosophical and administrative background of the foundation of the National Institute of Hygiene of the Bolivarian Republic of Venezuela

Higiene del griego "higieya", Diosa de la salud, es una doctrina médica y social, cuyos orígenes se remontan hasta los lejanos siglos del mundo greco-latino. En el presente trabajo se resumen las bases históricas, políticas y sociales que condujeron a la fundación de instituciones administrativas y científicas, cuyo fin fue organizar, así como llevar a cabo, programas que cumplieran con el objetivo de disminuir el riesgo de enfermedades causadas por conductas insanas y noxas del medio ambiente. La idea de higiene pública como una responsabilidad del Estado surgió fundamentalmente en el transcurso del siglo XVII y XVIII, y se sedimentó definitivamente a partir de la segunda mitad del siglo XIX. En el presente ensayo se hace una síntesis de algunos hechos históricos, científicos, sociales y políticos que condujeron definitivamente a la constitución de las actuales instituciones de higiene y de salud. Igualmente se resalta la personalidad humana y científica de algunos de los principales investigadores que sentaron las bases de la Higiene institucionalizada, fundando organizaciones que, en su mayor parte, han tenido una importante y positiva evolución, así como un impacto significativo en el devenir de los años subsiguientes. Entre ellos a nivel internacional se destacan investigadores como Max von Pettenkofer, Louis Pasteur, Paul Virchow y Robert Koch, así como a nivel nacional, Santos Aníbal Dominici, Rafael López Barala y Enrique Tejera Guevara. Así mismo, se expone una breve historia de varios de los Institutos de Higiene y de Salud que desde la última década del siglo XIX hasta el presente han aportado una significativa labor en la docencia, la investigación y amplia prestación de servicios de salud en Latinoamérica, algunos de ellos incluso previos a la fundación del Instituto Nacional de Higiene de Venezuela en 1938. Finalmente se menciona brevemente la amplia labor y el significativo apoyo que en todas esas labores ha prestado la Organización Panamericana de la Salud, o las organizaciones predecesoras,por más de 100 años

Hygiene from the Greek "higieya", Goddess of health, is a medical and social doctrine, whose origins go back to the distant centuries of the Greco-Latin world. This paper summarizes the historical, political and social bases that led to the foundation of administrative and scientific institutions, whose purpose was to organize, as well as carry out, programs that met the objective of reducing the risk of diseases caused by insane behaviors and noxious of the environment. The idea that public hygiene as a responsibility of the State arose mainly during the seventeenth and eighteenth centuries, and settled definitively from the second half of the nineteenth century. In the present essay a synthesis of some historical, scientific, social and political facts is made that definitively led to the constitution of the current hygiene and health institutions. Likewise, the human and scientific personality of some of the main researchers who laid the foundations of institutionalized hygiene is highlighted. These scientists founded significant organizations in subsequent years. Among the outstanding researchers we have Max von Pettenkofer, Louis Pasteur, Paul Virchow and Robert Koch. Santos Anibal Dominici, Rafael Lopez Barala and Enrique Tejera Guevara stand out with health scientists in Venezuela. In addition, this paper briefly exposes the history of various health and health institutions in the world and Latin America (nineteenth century - twentieth century). These institutions have contributed significant work in teaching, research and health services. In some cases, the construction and operation of these institutions was prior to the founding of the National Institute of Hygiene of Venezuela (1938). Finally, the work and significant support of the Pan American Health Organization to these institutions for more than 100 years is highlighted

Desarrollo histórico y logros de la Gerencia de Docencia e Investigación del Instituto Nacional de Higiene "Rafael Rangel" / Historical development and achievements of the Teaching and Research Management of the National Institute of Hygiene "Rafael Rangel"

La Gerencia de Docencia e Investigación es creada en el año 1992. Actualmente está conformada por la Coordinación de Postgrado, Coordinación de Investigación, Coordinación de Extensión, Pasantías, Campus Virtual, Departamento de Información y Divulgación Científica. La Gerencia tiene las siguientes funciones fundamentales: Programar, diseñar, coordinar y asesorar líneas de investigación, proyectos de investigación y producción de conocimiento científico de acuerdo a las políticas institucionales y del estado en el Sector Salud. Planificar y ejecutar programas docentes de 4to y 5to nivel, conducentes y no conducentes a grado académico en las áreas de competencia del Instituto. Programar y ejecutar la formación y capacitación del talento humano especializado, mediante diplomados, talleres, entrenamientos, simposia, jornadas, ampliación, actualización, perfeccionamiento profesional y extensión en el área de Salud. Gestionar y evaluar la formación y capacitación de talento humano procedente de instituciones educativas y de salud, mediante pasantías académicas y profesionales. Planificar, programar, coordinar, ejecutar y supervisar todas aquellas actividades, espacios y aulas virtuales de interacción, aprendizaje e-learning, trabajos en red, consultorías y tutorías telemáticas, acceso a materiales didácticos on-line, telebibliotecas, entre otros, tanto para el campus virtual de la Institución, como del Campus Virtual de Salud Pública Nodo Venezuela (éste último con otros organismos y apoyo de la Organización Panamericana de la Salud), enfocado a la formación y desarrollo de las competencias técnico-profesionales de los trabajadores en servicio y de las capacidades de las instituciones dedicadas a la prestación de servicios de salud pública en un formato virtual/semipresencial, brindando nuevas posibilidades de aprendizajes en entornos innovadores. Suministrar información especializada en el área de la salud, a través de servicios de divulgación, bibliotecarios, de documentación, edición de publicaciones e interactuar con otros centros de información científica para el cumplimiento de estos objetivos. Desarrollar y participar en las actividades de la Biblioteca Virtual en Salud de la OPS/BIREME. Preservación del Acervo Histórico Institucional. Este artículo contiene los siguientes aspectos: Antecedentes históricos de la Gerencia de Docencia e Investigación. Logros y desarrollo en el período 2008-2018. Reflexiones sobre la Política y los Planes de Formación del Instituto Nacional de Higiene "Rafael Rangel".

The Teaching and Research Management was created in 1992. It is currently made up of the Postgraduate Coordination, Research Coordination, Extension Coordination, Internships, Virtual Campus, Department of Information and Scientific Dissemination. Management has the folwloing fundamental functions: Schedule, design, coordinate and advise on research lines, research projects and production of scientific knowledge according to institutional and state policies in the Health Sector. Plan and execute teaching programs of 4th and 5th level, conducive and not conducive to academic degree in the areas of competence of the Institute. Schedule and execute the training and training of specialized human talent, through diplomas, workshops, training, symposia, conferences, expansion, updating, professional development and extension in the area of Health. Manage and evaluate the training and training of human talent from educational and health institutions, through academic and professional internships. Plan, program, coordinate, execute and supervise all those activities, spaces and virtual classrooms for interaction, e-learning learning, networking, consultancies and telematics tutorials, access to on-line teaching materials, tele-libraries, among others, for both the institution's virtual campus, such as the Virtual Campus of Public Health Nodo Venezuela (the latter with other organizations and support of the Pan American Health Organization), focused on the training and development of technical-professional skills of workers in service and of the capacities of the institutions dedicated to the provision of public health services in a virtual / blended format, providing new possibilities for learning in innovative environments. Provide specialized information in the area of health, through outreach services, librarians, documentation, publishing publications and interact with other scientific information centers for the fulfillment of these objectives. Develop and participate in the activities of the Virtual Health Library of PAHO / BIREME. Preservation of the Historical Institutional Collection. This article contains the following aspects: Historical background of the Teaching and Research Management. Achievements and development in the period 2008-2018. Reflections on the Policy and Training Plans of the National Institute of Hygiene "Rafael Rangel".

Radiolucencies surrounding acetabular components with three-dimensional coatings: artifact or real?

BACKGROUND: Several 2-dimensional and 3-dimensional surfaces are available for cementless acetabular fixation. Plain radiographs are used to assess osseointegration; however, the radiographs are limited by their inability to capture the bone fixation process occurring over the 3-dimensional cup surface. In this cadaveric study, we compared the bone apposition between 2-dimensional and 3-dimensional cups. METHODS: Both types of cups were implanted in 6 cadavers and pelvic radiographs obtained. Each cup was resected from the pelvis with adequate bone around it, and subsequently embedded in a polymer. Six sections of each cup were obtained to examine the metal and bone interface. Photographs and contact radiograph images were obtained for each section, and these were graded to arrive at percent metal-bone contact values for the cups. RESULTS: On average, <30% of the cups' areas displayed radiolucencies on the pelvic radiographs for both cup types. For the section images and radiographs, there was about 80% aggregate contact between the cups and surrounding bone in both cup types. In the 3-dimensional cups group, some inconsistencies were found between the section photographs and the corresponding radiograph images. The radiolucencies observed on the section radiograph could not always be correlated with metal to bone gap on the section photograph. CONCLUSIONS: Good metal-bone contact (75% + contact area) was observed on both cup types. The inconsistencies found in the 3-dimensional cup group may be because of the interaction of radiographs with the unique porous cup surface resulting in artifactual radiolucencies.

Lateral Hypothalamic GABAergic Neurons Encode Reward Predictions that Are Relayed to the Ventral Tegmental Area to Regulate Learning.

Eating is a learned process. Our desires for specific foods arise through experience. Both electrical stimulation and optogenetic studies have shown that increased activity in the lateral hypothalamus (LH) promotes feeding. Current dogma is that these effects reflect a role for LH neurons in the control of the core motivation to feed, and their activity comes under control of forebrain regions to elicit learned food-motivated behaviors. However, these effects could also reflect the storage of associative information about the cues leading to food in LH itself. Here, we present data from several studies that are consistent with a role for LH in learning. In the first experiment, we use a novel GAD-Cre rat to show that optogenetic inhibition of LH γ-aminobutyric acid (GABA) neurons restricted to cue presentation disrupts the rats' ability to learn that a cue predicts food without affecting subsequent food consumption. In the second experiment, we show that this manipulation also disrupts the ability of a cue to promote food seeking after learning. Finally, we show that inhibition of the terminals of the LH GABA neurons in ventral-tegmental area (VTA) facilitates learning about reward-paired cues. These results suggest that the LH GABA neurons are critical for storing and later disseminating information about reward-predictive cues.