A behavioral tagging account of kinase contribution to memory formation after spaced aversive training.

Long-term memory (LTM) can be induced by repeated spaced training trials. Using the weak inhibitory avoidance (wIA) task, we showed that one wIA session does not lead to a 24-h LTM, whereas two identical wIA sessions spaced by 15 min to 6 h induce a 24-h LTM. This LTM promotion depends both on hippocampal protein synthesis and the activity of several kinases. In agreement with the behavioral tagging (BT) hypothesis, our results suggest that the two training sessions induce transient learning tags and lead, via a cooperative effect, to the synthesis of plasticity-related proteins (PRPs) that become available and captured by the tag from the second session. Although ERKs1/2 are needed for PRPs synthesis and CaMKs are required for tag setting, PKA participates in both processes. We conclude that the BT mechanism accounts for the molecular constraints underlying the classic effect of spaced learning on LTM formation.

Behavioral tagging as a mechanism for aversive-memory formation under acute stress.

The behavioral tagging (BT) hypothesis postulates that a weak learning experience, which only induces short-term memory, may benefit from another event that provides plasticity-related proteins (PRPs) to establish a long-lasting memory. According to BT, the weak experience sets a transient learning tag at specific activated sites, and its temporal and spatial convergence with the PRPs allows the long-term memory (LTM) formation. In this work, rats were subjected to a weak inhibitory avoidance (IAw) training and we observed that acute stress (elevated platform, EP) experienced 1 hr before IAw promoted IA-LTM formation. This effect was dependent on glucocorticoid-receptor activity as well as protein synthesis in the dorsal hippocampus. However, the same stress has negative effects on IA-LTM formation when training is strong, probably by competing for necessary PRPs. Furthermore, our experiments showed that EP immediately after training did not impair the setting of the learning tag and even facilitated IA-LTM formation. These findings reveal different impacts of a given acute stressful experience on the formation of an aversive memory that could be explained by BT processes.

Spatial-Memory Formation After Spaced Learning Involves ERKs1/2 Activation Through a Behavioral-Tagging Process.

The superiority of spaced over massed learning is an established fact in the formation of long-term memories (LTM). Here we addressed the cellular processes and the temporal demands of this phenomenon using a weak spatial object recognition (wSOR) training, which induces short-term memories (STM) but not LTM. We observed SOR-LTM promotion when two identical wSOR training sessions were spaced by an inter-trial interval (ITI) ranging from 15 min to 7 h, consistently with spaced training. The promoting effect was dependent on neural activity, protein synthesis and ERKs1/2 activity in the hippocampus. Based on the "behavioral tagging" hypothesis, which postulates that learning induces a neural tag that requires proteins to induce LTM formation, we propose that retraining will mainly retag the sites initially labeled by the prior training. Thus, when weak, consecutive training sessions are experienced within an appropriate spacing, the intracellular mechanisms triggered by each session would add, thereby reaching the threshold for protein synthesis required for memory consolidation. Our results suggest in addition that ERKs1/2 kinases play a dual role in SOR-LTM formation after spaced learning, both inducing protein synthesis and setting the SOR learning-tag. Overall, our findings bring new light to the mechanisms underlying the promoting effect of spaced trials on LTM formation.

Effectiveness of Two Dietary Approaches on the Quality of Life and Gastrointestinal Symptoms of Individuals with Irritable Bowel Syndrome.

To evaluate the effectiveness of a low FODMAP (fermentable oligosaccharides, monosaccharaides, disaccharides and polyols) diet in the relief of symptoms and an improvement of the quality of life in individuals with irritable bowel syndrome in comparison to a standard diet according to the British Dietetic Association's guidelines. A non-randomized clinical trial of adult patients with IBS was compared two diet interventions. An assessment of symptoms, quality of life, and nutritional status was performed before and after the four-week mark of intervention. Individuals from the Low FODMAP Diet (LFD) group were evaluated on a third moment, after the controlled reintroduction of FODMAPs. A total of 70 individuals were divided in two groups: Low FODMAP Diet (LFD; n = 47) and Standard Diet (SD; n = 23). 57 individuals completed the four-week intervention (LFD; n = 39; SD; n = 18). At the completion of four weeks, the symptoms improved in both groups (LFD: p < 0.01; DC: p < 0.05) but LFD led to a higher relief (p < 0.05), primarily with respect to abdominal pain and diarrhoea. Quality of life improved significantly in both groups, with no significant differences between SD vs LFD (p > 0.05). In the LFD group, the relief of symptoms observed at the four-week mark remained constant after reintroduction of FODMAPs. Both interventions seem to be effective for the relief of symptoms and quality of life, however LFD had higher effectiveness in the former. The results with LFD suggest it can be a preferred approach in individuals with diarrhoeal profile.

Activation of the G Protein-Coupled Estrogen Receptor (GPER) Increases Neurogenesis and Ameliorates Neuroinflammation in the Hippocampus of Male Spontaneously Hypertensive Rats.

It is known that spontaneously hypertensive rats (SHR) present a marked encephalopathy, targeting vulnerable regions such as the hippocampus. Abnormalities of the hippocampus of SHR include decreased neurogenesis in the dentate gyrus (DG), partial loss of neurons in the hilus of the DG, micro and astrogliosis and inflammation. It is also known that 17ß-estradiol (E2) exert neuroprotective effects and prevent hippocampal abnormalities of SHR. The effects of E2 may involve a variety of mechanisms, including intracellular receptors of the ERα and ERß subtypes or membrane-located receptors, such as the G protein-coupled estradiol receptor (GPER). We have now investigated the protective role of GPER in SHR employing its synthetic agonist G1. To accomplish this objective, 5 month-old male SHR received 150 µg/day of G1 during 2 weeks. At the end of this period, we analyzed neuronal progenitors by staining for doublecortin (DCX), and counted the number of glial fibrillary acidic protein (GFAP)-labeled astrocytes and Iba1-stained microglial cells by computerized image analysis. We found that G1 activation of GPER increased DCX+ cells in the DG and reduced GFAP+ astrogliosis and Iba1+ microgliosis in the CA1 region of hippocampus. We also found that the high expression of proinflammatory makers IL1ß and cyclooxygenase 2 (COX2) of SHR was decreased after G1 treatment, which correlated with a change of microglia phenotype from the activated to a resting morphology. Additionally, G1 treatment increased the anti-inflammatory factor TGFß in SHR hippocampus. Altogether, our results suggest that activation of GPER plays a neuroprotective role on the encephalopathy of SHR, an outcome resembling E2 effects but avoiding secondary effects of the natural hormone.

Reparación laparoscópica de hernia hiatal gigante: técnica quirúrgica y seguimiento clínico, endoscópico y radiológico / Laparoscopic repair of giant hiatal hernia: surgical technique, and clinical, endoscopic and radiological follow-up

Introducción. La reparación laparoscópica es el estándar de tratamiento en hernia hiatal gigante. Sin embargo, a pesar de su baja morbilidad, la tasa de recurrencia sigue siendo alta. Nuestro objetivo fue describir los resultados de la reparación laparoscópica de hernia hiatal gigante, independientemente de la técnica de cruroplastia empleada.Métodos. Se llevó a cabo un estudio retrospectivo de pacientes llevados a reparación laparoscópica de hernia hiatal gigante en el periodo 2009-2017. Se analizaron los datos demográficos, la técnica quirúrgica, las complicaciones y la estancia hospitalaria. Se revisaron los resultados de la endoscopia, la radiografía de vías digestivas altas y la escala de síntomas GERD-HRQOL, obtenidos luego de un año de cirugía. Resultados. Se incluyeron 44 pacientes con un tamaño promedio de la hernia de 7 cm. Se practicó cruroplastia con sutura simple en 36,4 %, sutura más refuerzo con politetrafluoroetileno (PTFE) o dacrón, en 59,1 %, y se usó malla en 4,5 %. Hubo 12 complicaciones, la estancia hospitalaria promedio fue de 3,5 días y no hubo mortalidad. Se encontró recurrencia endoscópica o radiológica en 6/20 pacientes, todas pequeñas y asintomáticas. En 23 pacientes, la escala GERD-HRQOL reportó un valor promedio de 7,7 y 78 % de satisfacción. Solo un paciente requirió cirugía de revisión. Conclusión. El método preferido de reparación laparoscópica de la hernia hiatal gigante es la cruroplastia sin malla, técnica asociada a baja morbilidad y adecuado control de los síntomas. La tasa de recurrencia es similar a la reportada en la literatura. Se requieren estudios prospectivos con seguimiento completo a largo plazo para validar estos resultados

Introduction: Laparoscopic repair is the standard treatment for giant hiatal hernia. However, despite its low morbidity, recurrence rate remains high. Our goal was to describe the results of laparoscopic repair of giant hiatal hernia, regardless of the technique used for cruroplasty.Methods: A retrospective study of patients undergoing laparoscopic repair of giant hiatal hernia was carried out from 2009 to 2017. Demographic data, surgical technique, complications, and hospital stay were analyzed. The results of endoscopy, radiography of upper digestive tract, and GERD-HRQOL symptoms scale, obtained after one year of surgery, were reviewed.Results: Forty-four patients with an average hernia size of 7 cm were included. Simple suture cruroplasty was performed in 36.4%, suture plus reinforcement with polytetrafluoroethylene (PTFE) or Dacron in 59.1%, and mesh repair in 4.5%. There were 12 complications, the average hospital stay was 3.5 days, and there was no mortality. Endoscopic or radiological recurrence was found in 6/20 patients, all small and asymptomatic. In 23 patients, the GERD-HRQOL scale reported an average value of 7.7 and 78% patient satisfaction. Only one patient required revision surgery.Conclusion: The preferred method of laparoscopic repair of giant hiatal hernia is meshless cruroplasty, a technique associated with low morbidity and adequate symptom control. The recurrence rate is similar to that reported in the literature. Prospective studies with long-term follow-up are required to validate these results

Radiografía de tórax de control en pacientes con neumotórax postraumático asintomático / Follow-up chest x-ray in patients with asymptomatic post-traumatic pneumothorax

Introducción. El trauma de tórax tiene alta incidencia y el neumotórax es el hallazgo más frecuente. La literatura es escasa sobre qué hacer con los pacientes asintomáticos y con neumotórax por trauma de tórax penetrante. El objetivo de este estudio fue evaluar cuáles son los hallazgos de la radiografía de control de los pacientes con trauma de tórax penetrante que no son llevados inicialmente a cirugía, y su utilidad para determinar la necesidad de un tratamiento adicional. Métodos. Se realizó un estudio retrospectivo de cohorte, incluyendo pacientes mayores de 15 años que ingresaron por trauma de tórax penetrante entre enero de 2015 y diciembre de 2017 y que no requirieron manejo quirúrgico inicial. Se analizaron los resultados de la radiografía de tórax, el tiempo de su toma y la conducta decidida según los hallazgos en los pacientes dejados inicialmente bajo observación. Resultados. Se incluyeron 1.554 pacientes, cuya edad promedio fue de 30 años, 92,5 % del sexo masculino y 97% con herida por arma cortopunzante. Se dejaron 361 pacientes bajo observación con radiografía de control, de los cuales 186 (51,5 %) no presentaban alteraciones en su radiografía inicial, 142 tenían neumotórax menor del 30 % y 33 tenían neumotórax mayor del 30 %, hemoneumotórax o hemotórax. Se requirió toracostomía cerrada como conducta final en 78 casos, esternotomía o toracotomía en 2 casos y 281 se dieron de alta. Conclusión. En pacientes asintomáticos con neumotórax pequeño o moderado y sin otras lesiones significativas, podrían ser innecesarios los largos tiempos de observación, las radiografías y la toracostomía cerrada

Introduction: Chest trauma has a high incidence, and pneumothorax is the most frequent finding. The literature is limited about what to do with asymptomatic patients with pneumothorax due to penetrating chest trauma. The objective of this study was to evaluate the findings of control follow-up chest x-ray in patients with penetrating chest trauma who are not initially taken to surgery and its usefulness in determining the need for additional management.Methods: A retrospective cohort study was conducted, including patients older than 15 years who were admitted for penetrating chest trauma between January 2015 and December 2017 and who did not require initial surgical management. The results of the chest x-ray, the timing of it and the management according to the findings in the patients initially left under observation were analyzed.Results: 1,554 patients were included; whose average age was 30 years, 92.5% were males and 97% sustained a gunshot wound; 361 patients were left under observation with control x-ray, of which 186 (51,5%) had no findings on their initial radiograph, 142 had pneumothorax less than 30% and 33 had pneumothorax greater than 30%, hemoneumotorax or hemothorax. Closed thoracostomy was required as final management in 78 cases, sternotomy or thoracotomy in 2 cases and discharge in 281.Conclusion: In asymptomatic patients with small or moderate pneumothorax and without other significant injuries, longer observation times, x-rays and closed thoracostomy may be unnecessary

Management of duodenal trauma: A retrospective review from the Panamerican Trauma Society.

INTRODUCTION: The operative management of duodenal trauma remains controversial. Our hypothesis is that a simplified operative approach could lead to better outcomes. METHODS: We conducted an international multicenter study, involving 13 centers. We performed a retrospective review from January 2007 to December of 2016. Data on demographics, mechanism of trauma, blood loss, operative time, and associated injured organs were collected. Outcomes included postoperative intra-abdominal sepsis, leak, need for unplanned surgery, length of stay, renal failure, and mortality. We used the Research Electronic Data Capture tool to store the data. Poisson regression using a backward selection method was used to identify independent predictors of mortality. RESULTS: We collected data of 372 patients with duodenal injuries. Although the duodenal trauma was complex (median Injury Severity Score [ISS], 18 [interquartile range, 2-3]; Abbreviated Injury Scale, 3.5 [3-4]; American Association for the Surgery of Trauma grade, 3 [2-3]), primary repair alone was the most common type of operative management (80%, n = 299). Overall mortality was 24%. On univariate analysis, mortality was associated with male gender, lower admission systolic blood pressure, need for transfusion before operative repair, higher intraoperative blood loss, longer operative time, renal failure requiring renal replacement therapy, higher ISS, and associated pancreatic injury. Poisson regression showed higher ISS, associated pancreatic injury, postoperative renal failure requiring renal replacement therapy, the need for preoperative transfusion, and male gender remained significant predictors of mortality. Duodenal suture line leak was statistically significantly lower, and patients had primary repair over every American Association for the Surgery of Trauma grade of injury. CONCLUSIONS: The need for transfusion prior to the operating room, associated pancreatic injuries, and postoperative renal failure are predictors of mortality for patients with duodenal injuries. Primary repair alone is a common and safe operative repair even for complex injuries when feasible. LEVEL OF EVIDENCE: Therapeutic study, level IV.

[Development and validation of a predictive model for bacteremia in patients hospitalized by the emergency department with suspected infection]. / Desarrollo y validación de un modelo predictor para bacteriemia en pacientes hospitalizados por el servicio de urgencias con sospecha de infección.

BACKGROUND: Positive blood cultures usually indicate disseminated infection that is associated with a poor prognosis and higher mortality. We seek to develop and validate a predictive model to identify factors associated with positive blood cultures in emergency patients. METHODS: Secondary analysis of data from two prospective cohorts (EPISEPSIS: developing cohort, and DISEPSIS: validation cohort) of patients with suspected or confirmed infection, assembled in emergency services in 10 hospitals in four cities in Colombia between September 2007 and February 2008. A logistic multivariable model was fitted to identify clinical and laboratory variables predictive of positive blood culture. RESULTS: We analyzed 719 patients in developing and 467 in validation cohort with 32% and 21% positive blood cultures, respectively. The final predictive model included variables with significant coefficients for both cohorts: temperature > 38° C, Glasgow < 15 and platelet < 150.000 cells/mm³, with calibration (goodness-of-fit H-L) p = 0.0907 and p = 0.7003 and discrimination AUC = 0.68 (95% CI = 0.65-0.72) and 0.65 (95% CI = 0.61-0.70) in EPISEPSIS and DISEPSIS, respectively. Specifically, temperature > 38 °C and platelets < 150.000 cells/mm³ and normal Glasgow; or Glasgow < 15 with normal temperature and platelets exhibit a LR between 1,9 (CI 95% = 1,2-3,1) and 2,3 (CI 95% = 1,7-3,1). Glasgow < 15 with any of low platelets or high temperature shows a LR between 2,2 (CI 95% = 1,1-4,4) and 2,6 (CI 95% = 1,7-4,3). DISCUSSION: Temperature > 38° C, platelet count < 150,000 cells/mm³ and GCS < 15 are variables associated with increased likelihood of having a positive blood culture.

Desarrollo y validación de un modelo predictor para bacteriemia en pacientes hospitalizados por el servicio de urgencias con sospecha de infección / Development and validation of a predictive model for bacteremia in patients hospitalized by the emergency department with suspected infection

Background: Positive blood cultures usually indicate disseminated infection that is associated with a poor prognosis and higher mortality. We seek to develop and validate a predictive model to identify factors associated with positive blood cultures in emergency patients. Methods: Secondary analysis of data from two prospective cohorts (EPISEPSIS: developing cohort, and DISEPSIS: validation cohort) of patients with suspected or confirmed infection, assembled in emergency services in 10 hospitals in four cities in Colombia between September 2007 and February 2008. A logistic multivariable model was fitted to identify clinical and laboratory variables predictive of positive blood culture. Results: We analyzed 719 patients in developing and 467 in validation cohort with 32% and 21% positive blood cultures, respectively. The final predictive model included variables with significant coefficients for both cohorts: temperature > 38° C, Glasgow < 15 and platelet < 150.000 cells/mm³, with calibration (goodness-of-fit H-L) p = 0.0907 and p = 0.7003 and discrimination AUC = 0.68 (95% CI = 0.65-0.72) and 0.65 (95% CI = 0.61-0.70) in EPISEPSIS and DISEPSIS, respectively. Specifically, temperature > 38 °C and platelets < 150.000 cells/mm³ and normal Glasgow; or Glasgow < 15 with normal temperature and platelets exhibit a LR between 1,9 (CI 95% = 1,2-3,1) and 2,3 (CI 95% = 1,7-3,1). Glasgow < 15 with any of low platelets or high temperature shows a LR between 2,2 (CI 95% = 1,1-4,4) and 2,6 (CI 95% = 1,7-4,3). Discussion: Temperature > 38° C, platelet count < 150,000 cells/mm³ and GCS < 15 are variables associated with increased likelihood of having a positive blood culture.

Introducción: Un hemocultivo positivo usualmente indica infección diseminada, la que se asocia con peor pronóstico y mayor mortalidad. Por tanto, buscamos desarrollar y validar un modelo de predicción que permita identificar los factores asociados con la positividad de los hemocultivos en pacientes del servicio de urgencias. Métodos: Análisis secundario de datos de dos cohortes prospectivas (EPISEPSIS: cohorte de desarrollo y DISEPSIS: cohorte de validación) de pacientes con sospecha o confirmación de infección, ensambladas en servicios de urgencias de 10 instituciones hospitalarias en cuatro ciudades de Colombia entre septiembre de 2007 y febrero de 2008. Se ajustó un modelo logístico multivariado para identificar variables clínicas y de laboratorio predictoras de hemocultivos positivos. Resultados: Se analizaron 719 pacientes en la cohorte de desarrollo y 467 en la cohorte de validación, con 32 y 21% de hemocultivos positivos, respectivamente. El modelo predictor final incluyó las variables con coeficientes significativos para ambas cohortes: temperatura ≥ 38 °C, Glasgow < 15 y plaquetas ≤ 150.000 céls/mm³ con calibración (bondad de ajuste de H-L) p = 0,0907 y p = 0,7003 y discriminación AUC: 0,68 (IC 95%: 0,65-0,72) y 0,65 (IC 95%: 0,61-0,70) en EPISEPSIS y DISEPSIS, respectivamente. Temperatura ≥ 38 °C y recuento de plaquetas ≤ 150.000 céls/mm³ con Glasgow normal; o Glasgow < 15 con temperatura y plaquetas normales tiene un LR entre 1,9 (IC 95%: 1,2-3,1) y 2,3 (IC 95%: 1,7-3,1). La escala de Glasgow < 15 puntos junto con cualquiera entre recuento de plaquetas o temperatura alteradas tiene un LR entre 2,2 (IC 95%: 1,1-4,4) y 2,6 (IC 95%: 1,7-4,3). Discusión: La temperatura ≥ 38 °C, el recuento de plaquetas ≤ 150.000 céls/mm³ y la escala de Glasgow < 15 son las variables asociadas con mayor probabilidad de tener un hemocultivo positivo.