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Memory consolidation is an essential process of long-term memory formation. Neurotrophins have been suggested as key regulators of activity dependent changes in the synaptic efficacy and morphology, which are considered the downstream mechanisms of memory consolidation. The neurotrophin 3 (NT-3), a member of the neurotrophin family, and its high affinity receptor TrkC, are widely expressed in the insular cortex (IC), a region with a critical role in the consolidation of the conditioned taste aversion (CTA) paradigm, in which an animal associates a novel taste with nausea. Nevertheless, the role of this neurotrophin in the cognitive processes that the IC mediates remains unexamined. To answer whether NT-3 is involved in memory consolidation at the IC, adult male Wistar rats were administered with NT-3 or NT-3 in combination with the Trk receptors inhibitor K252a into the IC, immediately after CTA acquisition under two different conditions: a strong-CTA (0.2 M lithium chloride i.p.) or a weak-CTA (0.1 M lithium chloride i.p.). Our results show that NT-3 strengthens the memory trace of CTA, transforming a weak conditioning into a strong one, in a Trk-dependent manner. The present evidence suggests that NT-3 has a key role in the consolidation process of an aversive memory in a neocortical region.

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Environmental enrichment (EE) is known to improve memory and cognition and modulate the impact of aversive stimuli in animals, promoting the development of resilience to stressful situations. Likewise, it is known that EE can modulate synaptic plasticity as is the case of long-term potentiation (LTP). These findings have been described initially in ex vivo preparations, suggesting that the effects of EE are the result of an early modification of the synaptic excitability and transmission. In this regard, it is known that metaplasticity refers to the persistent modification, by previous activity, in the ability to induce synaptic plasticity. Our previous studies have shown that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of LTP in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC) in vivo. In addition, we have shown that CTA extinction allows the induction but not the maintenance of IC-LTP of the Bla-IC pathway. Recently, we also showed that prior exposure to environmental enrichment for three weeks reduces the strength of CTA, restoring the brain-derived neurotrophic factor (BDNF) levels in the IC. The present study aimed to analyze the effects of brief exposure to an enriched environment on the strength of aversive memory, as well as on the in vivo IC-LTP. To do so, adult rats were exposed for seven days to an EE, either before CTA training or LTP induction in the Bla-IC pathway. Our results demonstrate that a seven-day exposure to an enriched environment attenuates the aversive response to a strong CTA and allows the induction but not the maintenance of LTP in the insular cortex. These findings provide evidence that metaplastic regulation in a neocortical region takes part in the mechanisms through which brief exposure to enriched environments attenuates an aversive response.

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Cardioneural ablation is a novel treatment for functional bradycardia. However, the risk of acute complications is still unknown. The aim of this case report is to describe acute occlusion of the sinus node artery after cardiac denervation procedures in 2 patients and to encourage measures to prevent it, such as evaluating the aortic angulation in older patients before the procedure and by monitoring signs of sinus failure during ablation in patients with electroanatomical maps showing a constricted aspect of the right atrium. (Level of Difficulty: Advanced.).

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Purpose: Semi-automated lobar segmentation tools enable an anatomical assessment of regional pulmonary perfusion with Dual-Energy CTA (DE-CTA). We aimed to quantify lobar pulmonary perfusion with DE-CTA, analyze the perfusion distribution among the pulmonary lobes in subjects without cardiopulmonary diseases and assess the correlation between lobar perfusion and regional endoluminal clots in patients with acute pulmonary embolism (PE). Methods: We evaluated 151 consecutive subjects with suspected PE and without cardiopulmonary comorbidities. DE-CTA derived perfused blood volume (PBV) of each pulmonary lobe was measured applying a semi-automated lobar segmentation technique. In patients with PE, blood clot location was assessed, and CT-based vascular obstruction index of each lobe (CTOIlobe) was calculated and classified into three groups: CTOIlobe= 0, low CTOIlobe (1-50%) and high CTOIlobe (>50%). Results: Among patients without PE (103/151, 68.2%), median lobar PBV was 13.7% (IQR 10.2-18.0%); the right middle lobe presented lower PBV when compared to all the other lobes (p < .001). In patients with PE (48/151, 31.8%), lobar PBV was 12.6% (IQR 9.6-15.7%), 13.7% (IQR 10.1-16.7%) and 6.5% (IQR 5.1-10.2%) in the lobes with CTOIlobe= 0, low CTOIlobe and high CTOIlobe scores, respectively, with a significantly decreased PBV in the lobes with high CTOIlobe score (p < .001). ROC analysis of lobar PBV for prediction of high CTOIlobe score revealed AUC of 0.847 (95%CI 0.785-0.908). Conclusion: Pulmonary perfusion was heterogeneously distributed along the pulmonary lobes in patients without cardiopulmonary diseases. In patients with PE, the lobes with high vascular obstruction score (CTOIlobe> 50%) presented a decreased lobar perfusion.

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It has been shown that exposure to an enriched environment (EE) can modulate the physiological impact of aversive stimuli in animals, promoting adaptive attitudes, as well as the development of resilience to stressful situations. These changes are known to be related to increased levels of some trophic factors, such as brain-derived neurotrophic factor (BDNF), which has been considered a regulatory protein for synaptic plasticity in the adult brain. Our previous studies have demonstrated that in the insular cortex (IC), a brain region of the temporal lobe implicated in the acquisition, consolidation, and retention of conditioned taste aversion (CTA) task, BDNF can reverse the CTA memory deficit caused by a protein synthesis inhibitor. Likewise, our research group have also shown that BDNF is required for the maintenance of CTA long-term memory. Here we evaluate the effects of the exposure to an enriched environment on the CTA memory strength, using a weak and strong version of this paradigm. The exposure to an EE for 21 days was able to attenuate the strong-CTA response through the restoration of BDNF levels in the IC of adult rats. These results provide evidence that environmental enrichment is capable of reducing the strength of an aversive memory trace, restoring the BDNF levels in a neocortical region of the adult brain.

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Double right coronary artery (RCA) is an extremely uncommon anomaly that is mostly detected incidentally in patients undergoing coronary angiography. It can be a benign and isolated anomaly or associated with other congenital abnormalities, mostly other coronary anomalies. Although atherosclerosis and myocardial ischemia have been frequently reported in patients with double RCA, this likely reflects that the patients were evaluated for chest pain rather than the predisposition to atherosclerosis in double RCA. Paralleling the increased awareness of this entity and the availability of non-invasive and cost-effective imaging of the coronary arteries, the diagnosis of double RCA has increased recently. Here, we present a case of double RCA diagnosed by coronary computed tomographic angiography, and provide a mini-review on the demography, anatomic variants, and clinical significance of double RCA.

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Background and purpose: The novel coronavirus, SARS-CoV-2, which was identified after the outbreak in Wuhan, China, in December 2019, has kept the whole world in tenterhooks due to its severe life-threatening nature of the infection. The World Health Organization (WHO) declared coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 a pandemic in 2020, an unprecedented challenge, having a high contagious life-threatening condition with unprecedented impacts for worldwide societies and health care systems. Neurologic symptoms related to SARS-CoV-2 have been described recently in the literature, and acute cerebrovascular disease is one of the most serious complications. The occurrence of large-vessel occlusion in young patients with COVID-19 infection has been exceedingly rare. In this article, we describe the profile of patients undergoing decompressive craniectomy for the treatment of intracranial hypertension by stroke associated with COVID-19 published so far. A narrative review of the central issue in focus was designed: decompressive craniectomy in a pandemic time.

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BACKGROUND: Cerebrovascular disease is the fifth cause of mortality in Puerto Rico. There is no descriptive study for the presentation of spontaneous subarachnoid hemorrhage (SAH) in our institution. Therefore, our primary aim was to perform a retrospective analysis of adult patients with spontaneous SAH and assess the need for digital subtraction angiography (DSA) after initially aneurysm-negative computed tomography angiography (CTA) in nonaneurysmal SAH, specifically perimesencephalic SAH (PM-SAH). METHODS: Medical records of 324 adult patients with aneurysmal and nonaneurysmal SAH treated at the Puerto Rico Medical Center from 2015 to 2018 were retrospectively analyzed. Demographics, past medical history, clinical characteristics, and imaging information were extracted. RESULTS: Acute hydrocephalus, mortality at 30 days, prevalence of diffuse SAH pattern, and Fisher and World Federation of Neurosurgical Societies grades >2 on initial examination were higher in the aneurysmal SAH subgroup. Patients with nonaneurysmal SAH had a significantly higher prevalence of chronic kidney disease and diabetes mellitus. Of the patients with nonaneurysmal PM-SAH with initial aneurysm-negative CTA, 100% were subsequently confirmed by DSA. CONCLUSIONS: Patients in the aneurysmal SAH subgroup correlated with an increased disease burden. Furthermore, this study shows that in our population, patients with nonaneurysmal PM-SAH with a low Fisher and World Federation of Neurosurgical Societies grade and with comorbid diabetes mellitus and chronic kidney disease may not need DSA after a negative initial CTA result.

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Treatment of ascending aorta disease is surgical; however, some series have evaluated the effectiveness of endovascular treatment. We report the case of a patient with a ruptured pseudoaneurysm who underwent endovascular repair via the left common carotid artery. The clinical and neurological evolution was satisfactory during the in-hospital follow-up. (Level of Difficulty: Intermediate.).

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Este artigo é um relato de experiência de ações itinerantes de um Centro de Testagem e Aconselhamento (CTA) em ambiente universitário. Essas ações de aconselhamento e testagem foram possíveis a partir da interação entre a comunidade acadêmica e os profissionais de saúde do CTA, levando em consideração a noção de vulnerabilidade e suas categorias (individual, social e programática).

This article reports on experience of itinerant actions of a Testing and Counseling Center in a university environment. These counseling and testing actions were carried out through the interaction between an academic community and health professionals, taking into account the notion of vulnerability and its categories (individual, social and programmatic).

Este artículo es un relato de experiencia de acciones itinerantes de un Centro de Consejería y Pruebas en el ámbito universitario. Estas acciones de consejería y pruebas fueron posibles a partir de la interacción entre los profesionales de la salud y de la comunidad académica, teniendo en cuenta la noción de vulnerabilidad y sus categorías (individual, social y programática).

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The current view of the neurobiology of learning and memory suggests that long-term memory (LTM) depends not only on the de novo protein synthesis but also on the synthesis of mRNA even hours after the acquisition of memory, as well as that the regulation of transcription through the histone acetylation is essential for the memory establishment. Our previous studies showed that protein synthesis inhibition around the time of training and 5-7 hours after acquisition in the insular cortex (IC) prevents the consolidation of conditioned taste aversion (CTA), a well-established learning and memory paradigm in which an animal learns to associate a novel taste with nausea. However, the participation of mRNA synthesis and the epigenetic regulation through histone acetylation in this process remains unexplored. In the present study we evaluated the effect of the inhibition of transcription as well as deacetylation of histones at two temporal windows on the consolidation of CTA. Thus, immediately or seven hours after CTA acquisition animals received a microinfusion of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) or MS-275 in the IC, respectively. The present results show that transcription inhibition immediately and 7 h after acquisition impairs the CTA memory consolidation, whereas the inhibition of histone deacetylation strengths this memory at those temporal windows. These findings reveal that CTA memory requires recurrent rounds of transcriptional modulation events in the IC in order to consolidate this memory trace, demonstrating that transcriptional and epigenetic modulation substantially contribute to memory-consolidation-related functions performed by a neocortical area even several hours after memory acquisition.

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A 67-year-old man was sent to our center because of progressively worsening chest pain. A giant ruptured thoracic aortic aneurysm was documented. We performed a successfully rescue snorkel technique for thoracic endovascular aortic repair failure because of type IA endoleak after the first endoprosthesis implantation. The patient was discharged after 6 weeks. (Level of Difficulty: Advanced.).

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Accumulating evidence indicates that homeostatic plasticity mechanisms dynamically adjust synaptic strength to promote stability that is crucial for memory storage. Our previous studies have shown that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of long-term potentiation (LTP) in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC) in vivo. We have also reported that induction of LTP in the Bla-IC pathway modifies the CTA extinction. Memoryextinction involves the formation of a new associativememorythat inhibits a previously conditioned association. The aim of the present study was to analyze the effect of CTA extinction on the ability to induce subsequent LTP in the Bla-IC projection in vivo. Thus, 48 h after CTA extinction animals received high frequency stimulation in order to induce IC-LTP. Our results show that extinction training allows the induction but not the maintenance of IC-LTP. In addition, with the purpose of exploring part of the mechanisms involved in this process and since a body of evidence suggests that protein phosphatase calcineurin (CaN) is involved in the extinction of some behavioral tasks, we analyzed the participation of this phosphatase. The present results show that extinction training increases the CaN expression in the IC, as well as that the inhibition of this phosphatase reverts the effects of the CTA-extinction on the IC-LTP. These findings reveal that CTA extinction promotes a homeostatic regulation of subsequent IC synaptic plasticity maintenance through increases in CaN levels.

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BACKGROUND: Cardiac computed tomography angiography (cardiac CTA) is an increasingly used versatile imaging method to evaluate coronary and cardiac morphology. Owing to improvements in technology, image quality has continuously improved over the last 10-20 years. At the same time, numerous non-randomized and randomized studies have been performed to reduce the associated radiation exposure. Currently, it is unclear if the advances in technology and knowledge about radiation reduction translated into reduced levels of cardiac CTA radiation dose in daily clinical practice as well as a wide utilization of dose-saving strategies. METHODS: The PROTECTION VI study is a multicenter, prospective, worldwide registry designed to evaluate radiation dose exposure, utilization of dose-saving strategies and diagnostic image quality during cardiac CTA in current daily practice. Assessment of image quality will be addressed by the evaluation of diagnostic image quality at the local study site and the calculation of quantitative image quality parameters in an imaging core laboratory. Above 4000 patients will be enrolled from approximately 70 sites in Europe, North America, South America, Asia and Australia. The study will analyze median radiation dose levels, image quality, frequency of use and efficacy of algorithms for dose reduction, and patient and study-related predictors associated with radiation dose. CONCLUSIONS: The PROTECTION VI study is designed to provide a reliable estimate of current radiation dose for cardiac CTA and to assess the potential for additional dose reductions.

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Calcium-calmodulin/dependent protein kinase II (CaMKII) plays an essential role in LTP induction, but since it has the capacity to remain persistently activated even after the decay of external stimuli it has been proposed that it can also be necessary for LTP maintenance and therefore for memory persistence. It has been shown that basolateral amygdaloid nucleus (Bla) stimulation induces long-term potentiation (LTP) in the insular cortex (IC), a neocortical region implicated in the acquisition and retention of conditioned taste aversion (CTA). Our previous studies have demonstrated that induction of LTP in the Bla-IC pathway before CTA training increased the retention of this task. Although it is known that IC-LTP induction and CTA consolidation share similar molecular mechanisms, little is known about the molecular actors that underlie their maintenance. The purpose of the present study was to evaluate the role of CaMKII in the maintenance of in vivo Bla-IC LTP as well as in the persistence of CTA long-term memory (LTM). Our results show that acute microinfusion of myr-CaMKIINtide, a selective inhibitor of CaMKII, in the IC of adult rats during the late-phase of in vivo Bla-IC LTP blocked its maintenance. Moreover, the intracortical inhibition of CaMKII 24 h after CTA acquisition impairs CTA-LTM persistence. Together these results indicate that CaMKII is a central key component for the maintenance of neocortical synaptic plasticity as well as for persistence of CTA-LTM.

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BACKGROUND: The etiology of spontaneous dissection of coronary artery (SDCA) is not well understood yet. Different studies have linked this entity to pregnancy, physical stress, collagen diseases and vasculitis. In general, patients do not exhibit the classic risk factors for coronary artery disease, which mandates the suspicion of this condition, especially in young adults with acute coronary syndrome. CASE REPORT: In this article, we report the case of a 63-year old male patient, asymptomatic, who came for periodic evaluation and after evaluation by exercise and myocardial scintigraphy had high suspicion for severe coronary artery disease and underwent coronary angiography, which showed spontaneous dissection of the left and right branches of the coronary arteries. CONCLUSION: The choice of therapeutic strategies (clinics, percutaneous or surgical) remains uncertain and should be individualized by the features and form of presentation of the SDCA.

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Homeostatic plasticity mechanisms dynamically adjust synaptic strengths to promote stability that is crucial for memory storage. Metaplasticity is an example of these forms of plasticity that modify the capacity of synapses to experience subsequent Hebbian modifications. In particular, training in several behavioral tasks modifies the ability to induce long-term potentiation (LTP). Recently, we have reported that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of LTP generated by high frequency stimulation in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC). One of the key molecular players that underlie long-term synaptic plasticity is brain-derived neurotrophic factor (BDNF). Previous studies from our group reported that acute microinfusion of BDNF in the IC induces a lasting potentiation of synaptic efficacy at the Bla-IC projection. Thus, the aim of the present study was to analyze whether CTA training modifies the ability to induce subsequent BDNF-induced potentiation of synaptic transmission in the Bla-IC projection in vivo. Accordingly, CTA trained rats received intracortical microinfusion of BDNF in order to induce lasting potentiation 48h after the aversion test. Our results show that CTA training prevents the induction of in vivo BDNF-LTP in the Bla-IC projection. The present results provide evidence that CTA modulates BDNF-dependent changes in IC synaptic strength.

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Nowadays, it is known that brain derived neurotrophic-factor (BDNF) is a protein critically involved in regulating long-term memory related mechanisms. Previous studies from our group in the insular cortex (IC), a brain structure of the temporal lobe implicated in acquisition, consolidation and retention of conditioned taste aversion (CTA), demonstrated that BDNF is essential for CTA consolidation. Recent studies show that BDNF-TrkB signaling is able to mediate the enhancement of memory. However, whether BDNF into neocortex is able to enhance aversive memories remains unexplored. In the present work, we administrated BDNF in a concentration capable of inducing in vivo neocortical LTP, into the IC immediately after CTA acquisition in two different conditions: a "strong-CTA" induced by 0.2M lithium chloride i.p. as unconditioned stimulus, and a "weak-CTA" induced by 0.1M lithium chloride i.p. Our results show that infusion of BDNF into the IC converts a weak CTA into a strong one, in a TrkB receptor-dependent manner. The present data suggest that BDNF into the adult insular cortex is sufficient to increase an aversive memory-trace.

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Efforts to develop vaccines for prevention of acute diarrhea have been going on for more than 40 y with partial success. The myriad of pathogens, more than 20, that have been identified as a cause of acute diarrhea throughout the years pose a significant challenge for selecting and further developing the most relevant vaccine candidates. Based on pathogen distribution as identified in epidemiological studies performed mostly in low-resource countries, rotavirus, Cryptosporidium, Shigella, diarrheogenic E. coli and V. cholerae are predominant, and thus the main targets for vaccine development and implementation. Vaccination against norovirus is most relevant in middle/high-income countries and possibly in resource-deprived countries, pending a more precise characterization of disease impact. Only a few licensed vaccines are currently available, of which rotavirus vaccines have been the most outstanding in demonstrating a significant impact in a short time period. This is a comprehensive review, divided into 2 articles, of nearly 50 vaccine candidates against the most relevant viral and bacterial pathogens that cause acute gastroenteritis. In order to facilitate reading, sections for each pathogen are organized as follows: i) a discussion of the main epidemiological and pathogenic features; and ii) a discussion of vaccines based on their stage of development, moving from current licensed vaccines to vaccines in advanced stage of development (in phase IIb or III trials) to vaccines in early stages of clinical development (in phase I/II) or preclinical development in animal models. In this first article we discuss rotavirus, norovirus and Vibrio cholerae. In the following article we will discuss Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic), and Campylobacter jejuni.

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La nicotina es el ingrediente psicoactivo del tabaco y se ha descrito como aversiva, reforzante o procognitiva. Sin embargo no existe mucha investigación sobre el sobrelapamiento de los efectos dosis-dependientes como estímulo aversivo y procognitiva. Por lo que evaluaremos los efectos de la nicotina en el paradigma de condicionamiento aversivo al sabor (CAS), con el objetivo de obtener una curva dosis-respuesta del efecto aversivo y compararlo con los efectos procognitivos reportados. Se utilizaron 20 ratas macho Wistar asignadas aleatoriamente a cinco grupos (0.0, 0.2, 0.4, 0.8 y 1.6 mg/kg i.p.). Los resultados muestran tendencia al decremento dosis-dependiente con efecto máximo en la dosis de 1.6 mg/kg, sin embargo se hallaron efectos a partir de la dosis de 0.8 mg/kg lo cual sobrelapa con las dosis propuestas con efectos procognitivos. Esto nos permite proponer que algunos efectos puedan deberse a efectos aversivos periféricos más que a centrales.

Nicotine is the main ingredient of tobacco and it has been described as aversive, reinforce and procognitive. However there is not enough research about the overlapping of the dose-dependent effects as aversive stimulus and precognitive effects. For those reasons we evaluated the nicotine effects on the Conditioned Taste Aversion paradigm (CTA) to evaluated the dose-response curve of the aversive effects of nicotine and to compare such effects with the procognitive effects reported. 20 male Wistar rats in standard laboratory conditions were randomly assigned to 5 groups (0.0, 0.2, 0.4, 0.8 y 1.6 mg/kg i.p.). The obtained results showed a dose-dependent decrease with a maximum effect at 1.6 mg/kg dose, however we founded effects from the 0.8 mg/kg dose, such dose overlapped with procognitive doses reported. These results allow us to propose that some effects could be due the periferical aversive effects instead of the central procognitive effects.