Nucleus accumbens neurons dynamically respond to appetitive and aversive associative learning.

To survive, individuals must learn to associate cues in the environment with emotionally relevant outcomes. This association is partially mediated by the nucleus accumbens (NAc), a key brain region of the reward circuit that is mainly composed by GABAergic medium spiny neurons (MSNs), that express either dopamine receptor D1 or D2. Recent studies showed that both populations can drive reward and aversion, however, the activity of these neurons during appetitive and aversive Pavlovian conditioning remains to be determined. Here, we investigated the relevance of D1- and D2-neurons in associative learning, by measuring calcium transients with fiber photometry during appetitive and aversive Pavlovian tasks in mice. Sucrose was used as a positive valence unconditioned stimulus (US) and foot shock was used as a negative valence US. We show that during appetitive Pavlovian conditioning, D1- and D2-neurons exhibit a general increase in activity in response to the conditioned stimuli (CS). Interestingly, D1- and D2-neurons present distinct changes in activity after sucrose consumption that dynamically evolve throughout learning. During the aversive Pavlovian conditioning, D1- and D2-neurons present an increase in the activity in response to the CS and to the US (shock). Our data support a model in which D1- and D2-neurons are concurrently activated during appetitive and aversive conditioning.

Online learning in Health Professions Education. Part 1: Teaching and learning in online environments: AMEE Guide No. 161.

Online learning in Health Professions Education (HPE) has been evolving over decades, but COVID-19 changed its use abruptly. Technology allowed necessary HPE during COVID-19, but also demonstrated that many HP educators and learners had little knowledge and experience of these complex sociotechnical environments. Due to the educational benefits and flexibility that technology can afford, many higher education experts agree that online learning will continue and evolve long after COVID-19. As HP educators stand at the crossroads of technology integration, it is important that we examine the evidence, theories, advantages/disadvantages, and pedagogically informed design of online learning. This Guide will provide foundational concepts and practical strategies to support HPE educators and institutions toward advancing pedagogically informed use of online HPE. This Guide consists of two parts. The first part will provide an overview of evidence, theories, formats, and educational design in online learning, including contemporary issues and considerations such as learner engagement, faculty development, inclusivity, accessibility, copyright, and privacy. The second part (to be published as a separate Guide) focuses on specific technology tool types with practical examples for implementation and integration of the concepts discussed in Guide 1, and will include digital scholarship, learning analytics, and emerging technologies. In sum, both guides should be read together, as Guide 1 provides the foundation required for the practical application of technology showcased in Guide 2.Please refer to the video abstract for Part 1 of this Guide at https://bit.ly/AMEEGuideOnlineLearning.

Online learning in health professions education. Part 2: Tools and practical application: AMEE Guide No. 163.

Part 1 of the AMEE Guide Online learning in health professions education focused on foundational concepts such as theory, methods, and instructional design in online learning. Part 2 builds upon Part 1, introducing technology tools and applications of these foundational concepts by exploring the various levels (from beginner to advanced) of utilisation, while describing how their usage can transform Health Professions Education. This Part covers Learning Management Systems, infographics, podcasting, videos, websites, social media, online discussion forums, simulation, virtual patients, extended and virtual reality. Intertwined are other topics, such as online small group teaching, game-based learning, FOAM, online social and collaboration learning, and virtual care teaching. We end by discussing digital scholarship and emerging technologies. Combined with Part 1, the overall aim of Part 2 is to produce a comprehensive overview to help guide effective use online learning in Health Professions Education.

Occurrence and predictors of delirium in critically ill older patients: a prospective cohort study.

Objectives: This study aims to analyze the occurrence of delirium in critically ill older patients and to identify predictors of delirium. Methods: This prospective study included critically ill older patients admitted into level II units of Intensive Care Medicine Department of a University Hospital. Patients with Glasgow Coma Scale score ≤11, traumatic brain injury, terminal disease, history of psychosis, blindness/deafness, or inability to understanding/speaking Portuguese were excluded. The Confusion Assessment Method-Short Form (CAM-4) was used to assess the presence of delirium. Results: The final sample (n = 105) had a median age of 80 years, most being female (56.2%), widowed (49.5%), and with complete primary education (53%). Through CAM-4, 36.2% of the patients had delirium. The delirium group was more likely to have previous cognitive decline (48.6% vs 19.6%, P = .04) and severe dependency in instrumental activities of daily living (34.3% vs 14.8%, P = .032), comparing with patients without delirium. The final multiple logistic regression model explained that patients with previous cognitive decline presented a higher risk for delirium (odds ratio: 4.663, 95% confidence Interval: 1.055-20.599, P = .042). Conclusions: These findings corroborate previous studies, showing that cognitive decline is an independent predictor for delirium in older patients. This study is an important contribution for the knowledge regarding the predictors of delirium. The recognition of these factors will help to identify patients who are at high risk for this syndrome and implement early screening and prevention strategies. However, further studies with larger samples, recruited from other clinical settings as well as analyzing other potential factors for delirium, will be needed.

Involvement of nucleus accumbens D2-medium spiny neurons projecting to the ventral pallidum in anxiety-like behaviour.

BACKGROUND: The nucleus accumbens (NAcc) is a crucial brain region for emotionally relevant behaviours. The NAcc is mainly composed of medium spiny neurons (MSNs) expressing either dopamine receptor D1 (D1-MSNs) or D2 (D2-MSNs). The D1-MSNs project to the ventral tegmental area (VTA) and the ventral pallidum (VP), whereas the D2-MSNs project only to the VP. The D1- and D2-MSNs have been associated with depression-like behaviours, but their contribution to anxiety remains to be determined. METHODS: We used optogenetic tools to selectively manipulate D1-MSN projections from the NAcc core to the VP or VTA and D2-MSN projections to the VP during validated anxiety-producing behavioural procedures in naive mice. In addition, we assessed the effects of optical stimulation on neuronal activity using in vivo electrophysiologic recordings in anesthetized animals. RESULTS: Optogenetic activation of D1-MSN projections to the VTA or VP did not trigger anxiety-like behaviour. However, optical activation of D2-MSN projections to the VP significantly increased anxiety-like behaviour. This phenotype was associated with a decrease in the neuronal activity of putative GABAergic neurons in the VP. Importantly, pretreating D2-MSN-VP animals with the γ-aminobutyric acid modulator diazepam prevented the optically triggered anxiety-like behaviour. LIMITATIONS: The exclusive use of males in the behavioural tests limits broader interpretation of the findings. Although we used optogenetic conditions that trigger quasi-physiologic changes, there are caveats associated with the artificial manipulation of neuronal activity. CONCLUSION: The D2-MSN-VP projections contributed to the development of anxiety-like behaviour, through modulation of GABAergic activity in the VP.

Maternal diabetes affects rat offspring retinal structure and function: Sex-specific vulnerabilities at infancy.

AIMS: Maternal diabetes negatively impacts the offspring's brain, but little is known about its effects on the retina, which is also part of the central nervous system. We hypothesized that maternal diabetes adversely influences offspring retina development leading to structural and functional deficits. MAIN METHODS: Retinal structure and function were evaluated at infancy, by optical coherence tomography and electroretinography, in male and female offspring of control, diabetic and diabetic-treated with insulin Wistar rats. KEY FINDINGS: Maternal diabetes induced a delay in male and female offspring eye-opening, while insulin treatment expedited it. Structural analysis showed that maternal diabetes decreased the thickness of the inner and outer segment layer of photoreceptors in male offspring. Electroretinography also revealed that maternal diabetes decreased the amplitude of scotopic b-wave and flicker response in males, suggesting bipolar cells and cone photoreceptor dysfunction, an effect not observed in females. Conversely, maternal diabetes decreased cone arrestin protein levels in female retinas, while not affecting cone photoreceptor number. Dam insulin therapy was efficient in preventing the offspring photoreceptor changes. SIGNIFICANCE: Our results suggest that photoreceptors are affected by maternal diabetes, which may account for visual impairments at infancy. Notably, both male and female offspring presented specific vulnerabilities to hyperglycemia in this sensitive period of development.

Prenatal dexamethasone exposure alters effort decision making and triggers nucleus accumbens and anterior cingulate cortex functional changes in male rats.

Daily, individuals select actions based on cost-benefit to allocate resources into goal-directed actions. Different brain regions coordinate this complex decision, including the nucleus accumbens (NAc), anterior cingulate cortex (ACC), and ventral tegmental area (VTA). In utero exposure to synthetic glucocorticoids (iuGC), such as dexamethasone, triggers prominent motivation deficits but the impact of this exposure in the ACC-NAc and/or ACC-VTA circuits is unknown. Here, we show that iuGC exposure causes decreased motivation for natural rewards (food) and impaired effort-based decision-making. Importantly, reduced neuronal activation (number of c-fos+ neurons) was observed in the NAc core and ACC of iuGC rats in comparison to CTR rats after performing the effort-based decision-making task. In addition, iuGC treatment led to increased NAc and ACC basal neuronal activity. Electrophysiological recordings during optogenetic modulation of ACC terminals in the NAc revealed that the ACC-NAc circuit is dysfunctional in iuGC animals. These data suggest that iuGC animals present motivational and effort-based decision-making deficits that can be associated with the observed ACC-NAc dysfunction.

Distinct role of nucleus accumbens D2-MSN projections to ventral pallidum in different phases of motivated behavior.

The nucleus accumbens (NAc) is a key region in motivated behaviors. NAc medium spiny neurons (MSNs) are divided into those expressing dopamine receptor D1 or D2. Classically, D1- and D2-MSNs have been described as having opposing roles in reinforcement, but recent evidence suggests a more complex role for D2-MSNs. Here, we show that optogenetic modulation of D2-MSN to ventral pallidum (VP) projections during different stages of motivated behavior has contrasting effects in motivation. Activation of D2-MSN-VP projections during a reward-predicting cue results in increased motivational drive, whereas activation at reward delivery decreases motivation; optical inhibition triggers the opposite behavioral effect. In addition, in a free-choice instrumental task, animals prefer the lever that originates one pellet in opposition to pellet plus D2-MSN-VP optogenetic activation and vice versa for optogenetic inhibition. In summary, D2-MSN-VP projections play different, and even opposing, roles in distinct phases of motivated behavior.

Recall of delirium and related distress in elderly hospitalized patients: A prospective study.

Background: Delirium is a very common neuropsychiatric disorder in the elderly, with a significant physical and psychological burden. Much is still unknown about its psychological effects. This study aims to identify the proportion of patients who recall delirium and to analyze the distress caused by it. In addition, this study aims to analyze the association between delirium recall and related distress and global psychological distress regarding hospitalization. Methods: This is a prospective study with elderly hospitalized patients in level-2 units of intensive care medicine department of a university hospital. Exclusion criteria were a Glasgow Coma Scale total ≤11, brain injury, blindness, deafness, or inability to communicate. Delirium was daily assessed with the Confusion Assessment Method. Delirium recall and related distress in patients were measured using the Delirium Experience Questionnaire. Global psychological distress was assessed with the Kessler Psychological Distress Scale. Results: From 105 patients, 38 (36.2%) developed delirium. Most patients did not remember the delirium episode (64.7%). Among those who remembered (35.3%), most described delirium as a distressing experience (75%). Delirium recall was associated with high global psychological distress (P = .029). Conclusions: Distress related to delirium is high, namely in patients who recall the episode. Global psychological distress during hospitalization is associated with delirium recall. This study highlights the need to assess the experience of delirium in these patients, as well as the importance of providing support and psychological interventions to minimize the associated distress.

Laterodorsal tegmentum-ventral tegmental area projections encode positive reinforcement signals.

The laterodorsal tegmentum (LDT) is a brainstem nucleus classically involved in REM sleep and attention, and that has recently been associated with reward-related behaviors, as it controls the activity of ventral tegmental area (VTA) dopaminergic neurons, modulating dopamine release in the nucleus accumbens. To further understand the role of LDT-VTA inputs in reinforcement, we optogenetically manipulated these inputs during different behavioral paradigms in male rats. We found that in a two-choice instrumental task, optical activation of LDT-VTA projections shifts and amplifies preference to the laser-paired reward in comparison to an otherwise equal reward; the opposite was observed with inhibition experiments. In a progressive ratio task, LDT-VTA activation boosts motivation, that is, enhances the willingness to work to get the reward associated with LDT-VTA stimulation; and the reverse occurs when inhibiting these inputs. Animals abolished preference if the reward was omitted, suggesting that LDT-VTA stimulation adds/decreases value to the stimulation-paired reward. In addition, we show that LDT-VTA optical activation induces robust preference in the conditioned and real-time place preference tests, while optical inhibition induces aversion. The behavioral findings are supported by electrophysiological recordings and c-fos immunofluorescence correlates in downstream target regions. In LDT-VTA ChR2 animals, we observed an increase in the recruitment of lateral VTA dopamine neurons and D1 neurons from nucleus accumbens core and shell; whereas in LDT-VTA NpHR animals, D2 neurons appear to be preferentially recruited. Collectively, these data show that the LDT-VTA inputs encode positive reinforcement signals and are important for different dimensions of reward-related behaviors.

Interaction between Lactobacillus reuteri and periodontopathogenic bacteria using in vitro and in vivo (G. mellonella) approaches.

Periodontitis is a multifactorial inflammatory disease, and the major cause of tooth loss in adults. New therapies have been proposed for its treatment, including the use of probiotics such as Lactobacillus reuteri. The objective of this study was to evaluate the antimicrobial effects of L. reuteri: live, heat-killed and culture filtrate (cell-free supernatant), on periodontopathogenic bacteria (Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans) in vitro, as well as the in vivo survival curve, hemocyte density and microbial recovery using Galleria mellonella. For in vitro assays, all preparations reduced colony forming units of F. nucleatum, while only live L. reuteri reduced the growth of A. actinomycetemcomitans. All treatments reduced periodontopathogenic bacteria growth in vivo. The treatment with the supernatant increased the survival of larvae infected with F. nucleatum more than the treatment with live L. reuteri, and none of the treatments altered the survival of A. actinomycetemcomitans-infected larvae. In addition, the treatment with L. reuteri preparations did not alter the hemocyte count of F. nucleatum- and A. actinomycetemcomitans-infected larvae. This study demonstrated that L. reuteri preparations exerted antimicrobial effects and increased the survival of G. mellonella infected by F. nucleatum, although only live L. reuteri was able to reduce the growth of A. actinomycetemcomitans in vitro.

Abdominal Actinomycosis misdiagnosed as liposarcoma

Actinomycosis is an uncommon, endogenous, and chronic infection with varied and nonspecific clinical features such as abdominal, pelvic or cervical masses, ulcerative lesions, abscesses, draining fistula, fibrosis, and constitutional symptoms. The disease ensues when the bacteria disrupt the mucosal barrier, invade, and spread throughout interfascial planes. Currently, the diagnosis of actinomycosis is challenging because of its very low frequency and depending on the clinical presentation it may masquerade malignancies. Therapy consists initially in intravenous penicillin, followed by an oral regimen that may be extended until a year of treatment. A timely diagnosis is crucial to avoid extensive therapeutic attempt as surgery. However, a biopsy or drainage of abscesses and fistula's tract may be required not only as a diagnostic procedure as part of the therapy. We report the case of a 72-year-old woman with an abdominal mass initially misdiagnosed as a liposarcoma. A second biopsy of a skin lesion of the abdominal wall made the diagnosis of actinomycosis, avoiding a major surgical procedure. The patient was treated with a long-term course of antibiotics with favorable outcome. Liposarcoma was ruled out after the patient's full recovery with antibiotics and the misdiagnosis was credit to the overconfidence on the immunohistochemical positivity to MDM2.

Abdominal Actinomycosis misdiagnosed as liposarcoma.

Actinomycosis is an uncommon, endogenous, and chronic infection with varied and nonspecific clinical features such as abdominal, pelvic or cervical masses, ulcerative lesions, abscesses, draining fistula, fibrosis, and constitutional symptoms. The disease ensues when the bacteria disrupt the mucosal barrier, invade, and spread throughout interfascial planes. Currently, the diagnosis of actinomycosis is challenging because of its very low frequency and depending on the clinical presentation it may masquerade malignancies. Therapy consists initially in intravenous penicillin, followed by an oral regimen that may be extended until a year of treatment. A timely diagnosis is crucial to avoid extensive therapeutic attempt as surgery. However, a biopsy or drainage of abscesses and fistula's tract may be required not only as a diagnostic procedure as part of the therapy. We report the case of a 72-year-old woman with an abdominal mass initially misdiagnosed as a liposarcoma. A second biopsy of a skin lesion of the abdominal wall made the diagnosis of actinomycosis, avoiding a major surgical procedure. The patient was treated with a long-term course of antibiotics with favorable outcome. Liposarcoma was ruled out after the patient's full recovery with antibiotics and the misdiagnosis was credit to the overconfidence on the immunohistochemical positivity to MDM2.

Twelve tips for rapidly migrating to online learning during the COVID-19 pandemic.

This article was migrated. The article was marked as recommended. The COVID-19 pandemic has resulted in a massive adaptation in health professions education, with a shift from in-person learning activities to a sudden heavy reliance on internet-mediated education. Some health professions schools will have already had considerable educational technology and cultural infrastructure in place, making such a shift more of a different emphasis in provision. For others, this shift will have been a considerable dislocation for both educators and learners in the provision of education. To aid educators make this shift effectively, this 12 Tips article presents a compendium of key principles and practical recommendations that apply to the modalities that make up online learning. The emphasis is on design features that can be rapidly implemented and optimised for the current pandemic. Where applicable, we have pointed out how these short-term shifts can also be beneficial for the long-term integration of educational technology into the organisations' infrastructure. The need for adaptability on the part of educators and learners is an important over-arching theme. By demonstrating these core values of the health professions school in a time of crisis, the manner in which the shift to online learning is carried out sends its own important message to novice health professionals who are in the process of developing their professional identities as learners and as clinicians.

Sex differences in offspring neurodevelopment, cognitive performance and microglia morphology associated with maternal diabetes: Putative targets for insulin therapy.

Diabetes during pregnancy has been shown to affect the central nervous system (CNS) of the offspring, resulting in short- and long-term adverse effects. Children of diabetic mothers are more likely to develop cognitive impairment, also having increased susceptibility to psychiatric disorders. Microglia, the immune cells of the CNS, work as sensors of environmental changes, namely metabolic challenges, as early as the intrauterine period. During this period, microglia is actively involved in processes of neurogenesis, synaptic pruning and detection of any environmental alteration that may impact brain development. The remarkable sex dimorphism in neurodevelopment, as well as sex differences in the morphology and immune function of microglia during development, led us to clarify if maternal diabetes affects specific behavioral traits and microglia morphology during infancy in a sex-specific manner. Another important goal of this study was to clarify if insulin, the gold standard treatment of diabetes during gestation, could prevent maternal diabetes-induced behavioral changes, as well as microglia morphology, also considering sex specificities. Other molecular and cellular players potentially involved in the link between changes in metabolism and behavior were also analyzed in the hippocampus, a brain region implicated in cognition and other behavioral outcomes. Diabetes during pregnancy globally delayed female and male offspring development and was associated with impairments in recognition memory, but only in female offspring. In line with these results, at early and late infancy, some molecular and cellular markers were altered in offspring hippocampus in a sex-specific manner. The strict control of glycemia by insulin during pregnancy prevented most of the negative effects induced by uncontrolled hyperglycemia. Notably, insulin administration to diabetic dams may also modulate offspring development in a way that differs from what is observed in physiological conditions, since it promoted the expedited acquisition of developmental milestones and of discrimination ability at memory test, also inducing a hyper-ramification of male and female hippocampal microglia. Importantly, this study highlights the importance of analyzing the impact of maternal diabetes and insulin therapy, taking into account sex differences, since male and female present different vulnerabilities to hyperglycemia in this critical period of life.

Neuroendocrine tumor of the appendix-a case report and review of the literature.

Incidental appendiceal neuroendocrine tumors (ANETs) occur in 0.2-0.7% of surgical resections for suspected appendicitis (Moris, Tsilimigras, Vagios, Ntanasis-stathopoulos, Karachaliou, Papalampros, et al. Neuroendocrine neoplasms of the appendix: a review of the literature. Anticancer Res [Internet]. 2018;38:601-11.). It's a rare entity, clinically challenging and has controversy surrounding its management. A 69-year-old male presented to our clinic with acute right lower quadrant abdominal pain with less than 24 hours of evolution. The presumed clinical diagnosis was acute appendicitis. It was performed a laparoscopic appendectomy and the histopathologic result of the specimen showed neuroendocrine tumor of the appendix. ANETs are rare and typically diagnosed as incidental histopathologic finds in appendices specimens. However, they are the most common tumors arising from de appendix, between 30% and 80% of the cases (Pape, Niederle, Costa, Gross, Kelestimur, Kianmanesh, et al. ENETS consensus guidelines for neuroendocrine neoplasms of the appendix (excluding goblet cell carcinomas). Neuroendocrinology. 2016;103:144-52). Appendectomy may be sufficing for tumors <2 cm and they are associated with good long-term outcomes.

Small bowel obstruction due to intraluminal metastasis from malignant melanoma.

The most common form of presentation of malignant melanoma is cutaneous. However, it is important to notice that it can occur in any part of the body, mostly from metastatic route. Gastrointestinal forms of symptomatic metastasis are rare, making it sometimes difficult to diagnose. We present a rare case of an 84-year-old female with a small bowel obstruction due to melanoma metastasis. She was treated with an enterectomy, with no surgical or post-operative complications. Although surgery should be reserved from symptomatic patients, some authors refer to it as a palliative treatment with improvement in long-term survival.

Análise do acolhimento com classificação de risco em uma maternidade pública terciária de Fortaleza / Analysis of risk classification in a tertiary public maternity of Fortaleza

Objetivo: Analisar os atendimentos no acolhimento com classificação de risco em uma maternidade pública terciária de Fortaleza, Ceará. Metodologia: Estudo descritivo, retrospectivo, com abordagem quantitativa, que utilizou técnica de análise documental, com amostra de 365 instrumentos para classificação de risco, realizados no setor de emergência de uma maternidade pública terciária, no período de janeiro a junho de 2016. Resultados: A maioria (57,5%) das mulheres foi classificada como pouco urgente para o atendimento, sendo classificadas com a cor verde. As principais queixas nos atendimentos foram: dor (34,5%), sangramento vaginal (17,5%) e perda de líquido (14%). Conclusão: A clientela que busca atendimento precisa ser mais bem orientada sobre os sinais e sintomas do trabalho de parto, durante as consultas de pré-natal na atenção básica.

Objective: To analyze the host with risk classification in a tertiary public maternity hospital in Fortaleza, Ceará. Methodology: A descriptive, retrospective study with a quantitative approach using a documental analysis technique, with a sample of 365 instruments for risk classification, performed in the emergency sector of a tertiary public maternity hospital, from January to June, 2016. Results: The majority (57.5%) of the women were classified as not very urgent for care being classified as green. The main complaints were pain (34.5%), vaginal bleeding (17.5%) and fluid loss (14%). Conclusion: Clients seeking care need to be better informed about the signs and symptoms of labor during prenatal consultations in basic care.

Objetivo: Analizar la acogida con clasificación de riesgo en una maternidad pública terciaria de Fortaleza, Ceará. Metodología: Estudio descriptivo, retrospectivo, con abordaje cuantitativo, que utilizó técnica de análisis documental, con muestra de 365 instrumentos para clasificación de riesgo, realizados en el sector de emergencia de una maternidad pública terciaria, en el período de enero a junio de 2016. Resultados: La mayoría (57,5%) de las mujeres fue clasificada como poco urgente para la atención siendo clasificadas con el color verde. Las principales quejas en las atenciones fueron: dolor (34,5%), sangrado vaginal (17,5%) y pérdida de líquido (14%). Conclusión: La clientela que busca atención necesita ser mejor orientada sobre los signos y síntomas del trabajo de parto, durante las consultas de prenatal en la atención básica.

Parathyroid carcinoma: From a case report to a review of the literature.

INTRODUCTION: Parathyroid carcinoma is a rare endocrine malignancy. The reported incidence is from 0.5 to 5% of primary hyperparathyroidism cases in various series. Consideration of parathyroid carcinoma in the differential diagnosis of hypercalcaemic disorders is important because the morbidity and mortality are substantial and the best prognosis is associated with early recognition and surgical resection. PRESENTATION OF CASE: We report a case of parathyroid carcinoma occurring in a 60-year-old woman who presented to our institution with persistent hyperparathyroidism and hypercalcemia 3 years after being submitted to one gland parathyroidectomy in another hospital. DISCUSSION AND CONCLUSION: A review of the related literature follows.