A narrative review of adaptive testing and its application to medical education.

Adaptive testing has a long but largely unrecognized history. The advent of computer-based testing has created new opportunities to incorporate adaptive testing into conventional programmes of study. Relatively recently software has been developed that can automate the delivery of summative assessments that adapt by difficulty or content. Both types of adaptive testing require a large item bank that has been suitably quality assured. Adaptive testing by difficulty enables more reliable evaluation of individual candidate performance, although at the expense of transparency in decision making, and requiring unidirectional navigation. Adaptive testing by content enables reduction in compensation and targeted individual support to enable assurance of performance in all the required outcomes, although at the expense of discovery learning. With both types of adaptive testing, candidates are presented a different set of items to each other, and there is the potential for that to be perceived as unfair. However, when candidates of different abilities receive the same items, they may receive too many they can answer with ease, or too many that are too difficult to answer. Both situations may be considered unfair as neither provides the opportunity to demonstrate what they know. Adapting by difficulty addresses this. Similarly, when everyone is presented with the same items, but answer different items incorrectly, not providing individualized support and opportunity to demonstrate performance in all the required outcomes by revisiting content previously answered incorrectly could also be considered unfair; a point addressed when adapting by content. We review the educational rationale behind the evolution of adaptive testing and consider its inherent strengths and limitations. We explore the continuous pursuit of improvement of examination methodology and how software can facilitate personalized assessment. We highlight how this can serve as a catalyst for learning and refinement of curricula; fostering engagement of learner and educator alike.

Objective structured assessment ultrasound skill scale for hyomental distance competence - psychometric study.

BACKGROUND: Ultrasound assessment of the airway recently integrates the point-of-care approach to patient evaluation since ultrasound measurements can predict a difficult laryngoscopy and tracheal intubation. Because ultrasonography is performer-dependent, a proper training and assessment tool is needed to increase diagnostic accuracy. An objective, structured assessment ultrasound skill (OSAUS) scale was recently developed to guide training and assess competence. This work aims to study the psychometric properties of OSAUS Scale when used to evaluate competence in ultrasound hyomental distance (HMD) measurement. METHODS: Prospective and experimental study. Volunteers were recruited and enrolled in groups with different expertise. Each participant performed three ultrasonographic HMD evaluation. The performance was videorecorded and anonymized. Five assessors blindly rated participants' performance using OSAUS scale and a Global Rating Scale (GRS). A psychometric study of OSAUS scale as assessment tool for ultrasound HMD competence was done. RESULTS: Fifteen voluntaries participated on the study. Psychometric analysis of OSAUS showed strong internal consistency (Cronbach's alpha 0.916) and inter-rater reliability (ICC 0.720; p < 0.001). The novice group scored 15.4±0.18 (mean±SD), the intermediate 14.3±0.75 and expert 13.6±0.1.25, with a significant difference between novice and expert groups (p = 0.036). The time in seconds to complete the task was evaluated: novice (90±34) (mean±SD), intermediate (84±23) and experts (83±15), with no significant differences between groups. A strong correlation was observed between OSAUS and global rating scale (r = 0.970, p < 0.001). CONCLUSION: The study demonstrated evidence of validity and reliability. Further studies are needed to implement OSAUS scale in the clinical setting for training and assessment of airway ultrasound competence.

Feasibility assurance: a review of automatic item generation in medical assessment.

BACKGROUND: Current demand for multiple-choice questions (MCQs) in medical assessment is greater than the supply. Consequently, an urgency for new item development methods arises. Automatic Item Generation (AIG) promises to overcome this burden, generating calibrated items based on the work of computer algorithms. Despite the promising scenario, there is still no evidence to encourage a general application of AIG in medical assessment. It is therefore important to evaluate AIG regarding its feasibility, validity and item quality. OBJECTIVE: Provide a narrative review regarding the feasibility, validity and item quality of AIG in medical assessment. METHODS: Electronic databases were searched for peer-reviewed, English language articles published between 2000 and 2021 by means of the terms 'Automatic Item Generation', 'Automated Item Generation', 'AIG', 'medical assessment' and 'medical education'. Reviewers screened 119 records and 13 full texts were checked according to the inclusion criteria. A validity framework was implemented in the included studies to draw conclusions regarding the validity of AIG. RESULTS: A total of 10 articles were included in the review. Synthesized data suggests that AIG is a valid and feasible method capable of generating high-quality items. CONCLUSIONS: AIG can solve current problems related to item development. It reveals itself as an auspicious next-generation technique for the future of medical assessment, promising several quality items both quickly and economically.

ATENA-A Novel Rapidly Manufactured Medical Invasive Ventilator Designed as a Response to the COVID-19 Pandemic: Testing Protocol, Safety, and Performance Validation.

Background: The urgent need for mechanical ventilators to support respiratory insufficiency due to SARS-CoV-2 led to a worldwide effort to develop low-cost, easily assembled, and locally manufactured ventilators. The ATENA ventilator project was developed in a community-based approach targeting the development, prototyping, testing, and decentralized manufacturing of a new mechanical ventilator. Objective: This article aims to demonstrate ATENA's adequate performance and safety for clinical use. Material: ATENA is a low-cost ventilator that can be rapidly manufactured, easily assembled, and locally produced anywhere in the world. It was developed following the guidelines and requirements provided by European and International Regulatory Authorities (MHRA, ISO 86201) and National Authorities (INFARMED). The device was thoroughly tested using laboratory lung simulators and animal models. Results: The device meets all the regulatory requirements for pandemic ventilators. Additionally, the pre-clinical experiences demonstrated security and adequate ventilation and oxygenation, in vivo. Conclusion: The ATENA ventilator had a good performance in required tests in laboratory scenarios and pre-clinical studies. In a pandemic context, ATENA is perfectly suited for safely treating patients in need of mechanical ventilation.

Translation, adaptation and validation of the Mini-Clinical Evaluation Exercise to the EU-Portuguese language / Traducción, adaptación y validación del Mini-Clinical Evaluation Exercise (Mini-CEX) al idioma portugués europeo

INTRODUCTION: The goal of this work is to validate tools to assess clinical competences of undergraduate medical students in the workplace. One of the most well-known scales is the Mini-Clinical Evaluation Exercise (Mini-CEX). This scale has been vastly studied, however, its validity is very variable amongst studies and it has never been validated to the EU-Portuguese language and context. Subjects and methods: The translation process of the Mini-CEX was conducted by 2 bilingual individuals and overseen by four physicians specialized in medical education. We performed methods of both qualitative (translation, assessment of the translation, back translation) and quantitative nature (internal consistency, construct and content validity analysis). The scale was applied to 3rd year medical students in a simulated assessment environment with a final sample size of 818 assessments. RESULTS: The results show that the Portuguese version of the Mini-CEX is a valid scale and fit its purpose for the assessment of clinical competencies. The Cronbach's alpha coefficient (0.927), confirmed the internal consistency of the scale. Additionally, the validity analysis also proved to be satisfactory, with confirmatory results for all domains of the analysis. CONCLUSIONS: This work intends to provide a scale, translated, adapted and validated to Portuguese that is focused on clinical competencies. Given the confirmatory results of the scale's validity, supporting its feasibility and applicability, we believe this tool is ready to be implemented as a complement to clinical skills assessment

INTRODUCCIÓN: El objetivo de este trabajo es validar herramientas para evaluar las competencias clínicas de los estudiantes de medicina de pregrado en el lugar de trabajo. Una de las escalas más conocidas es el Mini-Clinical Evaluation Exercise (Mini-CEX). Esta escala se ha estudiado ampliamente, pero su validez es muy variable entre los estudios y nunca se ha validado para el idioma y el contexto portugués europeo. Sujetos y métodos: El proceso de traducción del Mini-CEX fue realizado por dos personas bilingües y supervisado por cuatro médicos especializados en educación médica. Se llevaron a cabo métodos de naturaleza cualitativa (traducción, evaluación de la traducción, traducción inversa) y cuantitativa (consistencia interna, construcción y análisis de validez de contenido). La escala se aplicó a estudiantes de medicina de tercer año en un entorno de evaluación simulada, con un tamaño final de la muestra de 818 evaluaciones. RESULTADOS: Los resultados muestran que la versión portuguesa del Mini-CEX es una escala válida y se ajusta a su propósito para la evaluación de las competencias clínicas. El coeficiente alfa de Cronbach (0,927) confirmó la consistencia interna de la escala. Además, el análisis de validez también demostró ser satisfactorio, con resultados confirmatorios para todos los dominios del análisis. CONCLUSIONES: Este trabajo pretende proporcionar una escala, traducida, adaptada y validada al portugués, que se centre en las competencias clínicas. Dados los resultados confirmatorios de la validez de la escala, que respaldan su viabilidad y aplicabilidad, creemos que esta herramienta está lista para implementarse como complemento de la evaluación de habi-lidades clínicas

Neurodevelopment impact of CO2-pneumoperitoneum in neonates: experimental study in a rat model.

BACKGROUND: Laparoscopy is becoming more common in neonates. However, concerns remain about the impact of the carbon-dioxide (CO2)-insufflation over the neonatal brain. We aim to evaluate the peripheral (serum) and central (cerebrospinal fluid [CSF]) cytokine response after neonatal CO2-pneumoperitoneum and its impact over neurodevelopmental milestones acquisition and long-term behavioral outcomes. MATERIALS AND METHODS: Rats were subjected to a systematic assessment of neurodevelopmental milestones between postnatal day 1 (PND 1) and PND 21. At PND 10, neonatal rats were anesthetized, mechanically ventilated, and exposed to different pressures and times of abdominal CO2-insufflation. Immediately after pneumoperitoneum, corticosterone was analyzed in serum. Twenty-four hours after intervention, serum and CSF were collected to assess inflammatory response (interleukin [IL]-10, IL-1ß, tumor necrosis factor [TNF]-α, and interferon [IFN]-γ). In adulthood, animals from each group were submitted to several tests to assess different behavioral domains (locomotion, anxiety, mood, and cognition). RESULTS: The antiinflammatory cytokine IL-10 was significantly increased in CSF in CO2-insufflated groups, with no other significant changes in the other biomarkers. Acquisition of neurodevelopmental milestones was maintained in all studied groups. No significant differences were observed in adult behavior in the different CO2-insufflation conditions. CONCLUSIONS: Neonatal CO2-pneumoperitoneum does not seem to have any negative impact on neurodevelopment or induce behavioral alterations in adulthood. Minimally invasive surgery results in a central antiinflammatory profile, and further studies on the functional consequences of these phenomena are needed.

Animal facility videoendoscopic intubation station: tips and tricks from mice to rabbits.

Endotracheal intubation of laboratory animals is a common procedure shared by several research fields for different purposes, such as mechanical ventilation of anaesthetized animals, instillation of cytotoxic nanoparticles, infectious agents or tumour cells for induction of disease models, and even for diagnostic and therapeutic purposes. These different research purposes, achieved in different animal models, require technical expertise and equipment that suits every research need from animal facilities. In this short report we propose a videoendoscopic intubation station that could be shared among the most common laboratory animals, namely the mouse, rat, guinea pig and rabbit, from neonates to adult animals. This report aims to contribute to the reduction of animals excluded from experiments due to false paths during direct and blind intubations and to the refinement of procedures by replacing surgical approaches such as tracheotomy.

Exposure to Ketamine Anesthesia Affects Rat Impulsive Behavior.

Introduction: Ketamine is a general anesthetic (GA) that activates several neurotransmitter pathways in various part of the brain. The acute effects as GA are the most well-known and sought-after: to induce loss of responsiveness and to produce immobility during invasive procedures. However, there is a concern that repeated exposure might induce behavioral changes that could outlast their acute effect. Most research in this field describes how GA affects cognition and memory. Our work is to access if general anesthesia with ketamine can disrupt the motivational behavior trait, more specifically measuring impulsive behavior. Methods: Aiming to evaluate the effects of exposure to repeat anesthetic procedures with ketamine in motivational behavior, we tested animals in a paradigm of impulsive behavior, the variable delay-to-signal (VDS). In addition, accumbal and striatal medium spiny neurons morphology was assessed. Results: Our results demonstrated that previous exposure to ketamine deep-anesthesia affects inhibitory control (impulsive behavior). Specifically, ketamine exposed animals maintain a subnormal impulsive rate in the initial periods of the delays. However, in longer delays while control animals progressively refrain their premature unrewarded actions, ketamine-exposed animals show a different profile of response with higher premature unrewarded actions in the last seconds. Animals exposed to multiple ketamine anesthesia also failed to show an increase in premature unrewarded actions between the initial and final periods of 3 s delays. These behavioral alterations are paralleled by an increase in dendritic length of medium spiny neurons of the nucleus accumbens (NAc). Conclusions: This demonstrates that ketamine anesthesia acutely affects impulsive behavior. Interestingly, it also opens up the prospect of using ketamine as an agent with the ability to modulate impulsivity trait.

Stress induced risk-aversion is reverted by D2/D3 agonist in the rat.

Stress exposure triggers cognitive and behavioral impairments that influence decision-making processes. Decisions under a context of uncertainty require complex reward-prediction processes that are known to be mediated by the mesocorticolimbic dopamine (DA) system in brain areas sensitive to the deleterious effects of chronic stress, in particular the orbitofrontal cortex (OFC). Using a decision-making task, we show that chronic stress biases risk-based decision-making to safer behaviors. This decision-making pattern is associated with an increased activation of the lateral part of the OFC and with morphological changes in pyramidal neurons specifically recruited by this task. Additionally, stress exposure induces a hypodopaminergic status accompanied by increased mRNA levels of the dopamine receptor type 2 (Drd2) in the OFC; importantly, treatment with a D2/D3 agonist quinpirole reverts the shift to safer behaviors induced by stress on risky decision-making. These results suggest that the brain mechanisms related to risk-based decision-making are altered after chronic stress, but can be modulated by manipulation of dopaminergic transmission.

Variable delay-to-signal: a fast paradigm for assessment of aspects of impulsivity in rats.

Testing impulsive behavior in rodents is challenging and labor-intensive. We developed a new behavioral paradigm-the Variable Delay-to-Signal (VDS) test-that provides rapid and simultaneous assessment of response and decision impulsivity in rodents. Presentation of a light at variable delays signals the permission for action (nose poke) contingent with a reward. 2 blocks of 25 trials at 3 s delay flank a block of 70 trials in which light is presented with randomly selected 6 or 12 s delays. Exposure to such large delays boosts the rate of premature responses when the delay drops to 3 s in the final block, an effect that is blunted by an acute methamphetamine challenge and that correlates with the delay-discounting (DD) paradigm (choice impulsivity). Finally, as expected, treatment with the NMDA antagonist MK-801 caused a generalized response increase in all VDS blocks. The pharmacological validation, particularly with methamphetamine which has a well established dual effect on response and decision impulsivity, and the correlations between the impulsive behavior in the DD and VDS paradigms, suggests that the later is able to provide, in a single session, a multi-dimensional assessment of impulsive behavior.

Neudesin is involved in anxiety behavior: structural and neurochemical correlates.

Neudesin (also known as neuron derived neurotrophic factor, Nenf) is a scarcely studied putative non-canonical neurotrophic factor. In order to understand its function in the brain, we performed an extensive behavioral characterization (motor, emotional, and cognitive dimensions) of neudesin-null mice. The absence of neudesin leads to an anxious-like behavior as assessed in the elevated plus maze (EPM), light/dark box (LDB) and novelty suppressed feeding (NSF) tests, but not in the acoustic startle (AS) test. This anxious phenotype is associated with reduced dopaminergic input and impoverished dendritic arborizations in the dentate gyrus granule neurons of the ventral hippocampus. Interestingly, shorter dendrites are also observed in the bed nucleus of the stria terminalis (BNST) of neudesin-null mice. These findings lead us to suggest that neudesin is a novel relevant player in the maintenance of the anxiety circuitry.

Behavioral characterization of the 6-hydroxidopamine model of Parkinson's disease and pharmacological rescuing of non-motor deficits.

BACKGROUND: Parkinson's disease (PD) is a chronic neurodegenerative condition that is characterized by motor symptoms as a result of dopaminergic degeneration, particularly in the mesostriatal pathway. However, in recent years, a greater number of clinical studies have focused on the emergence of non-motor symptoms in PD patients, as a consequence of damage on the mesolimbic and mesocortical dopaminergic networks, and on their significant impact on the quality of life of PD patients. Herein, we performed a thorough behavioral analysis including motor, emotional and cognitive dimensions, of the unilateral medial forebrain bundle (MFB) 6-hydroxidopamine (6-OHDA)-lesioned model of PD, and further addressed the impact of pharmacological interventions with levodopa and antidepressants on mood dimensions. RESULTS: Based on apomorphine-induced turning behaviour and degree of dopaminergic degeneration, animals submitted to MFB lesions were subdivided in complete and incomplete lesion groups. Importantly, this division also translated into a different severity of motor and exploratory impairments and depressive-like symptoms; in contrast, no deficits in anxiety-like and cognitive behaviors were found in MFB-lesioned animals. Subsequently, we found that the exploratory and the anhedonic behavioural alterations of MFB-lesioned rats can be partially improved with the administration of both levodopa or the antidepressant bupropion, but not paroxetine. CONCLUSIONS: Our results suggest that this model is a relevant tool to study the pathophysiology of motor and non-motor symptoms of PD. In addition, the present data shows that pharmacological interventions modulating dopaminergic transmission are also relevant to revert the non-motor behavioral deficits found in the disease.

Excitotoxic lesions in the central nucleus of the amygdala attenuate stress-induced anxiety behavior.

The extended amygdala, composed by the amygdaloid nuclei and the bed nucleus of the stria terminalis (BNST), plays a critical role in anxiety behavior. In particular, the link between the central nucleus of the amygdala (CeA) and the BNST seems to be critical to the formation of anxiety-like behavior. Chronic unpredictable stress (CUS) exposure is recognized as a validated animal model of anxiety and is known to trigger significant morphofunctional changes in the extended amygdala. Quite surprisingly, no study has ever analyzed the role of the CeA in the onset of stress-induced anxiety and fear conditioning behaviors; thus, in the present study we induced a bilateral excitotoxic lesion in the CeA of rats that were subsequently exposed to a chronic stress protocol. Data shows that the lesion in the CeA induces different results in anxiety and fear-behaviors. More specifically, lesioned animals display attenuation of the stress response and of stress-induced anxiety-like behavior measured in the elevated-plus maze (EPM) when compared with stressed animals with sham lesions. This attenuation was paralleled by a decrease of stress-induced corticosterone levels. In contrast, we did not observe any significant effect of the lesion in the acoustic startle paradigm. As expected, lesion of the CeA precluded the appearance of fear behavior in a fear-potentiated startle paradigm in both non-stressed and stressed rats. These results confirm the implication of the CeA in fear conditioning behavior and unravel the relevance of this brain region in the regulation of the HPA axis activity and in the onset of anxiety behavior triggered by stress.

Stress shifts the response of the bed nucleus of the stria terminalis to an anxiogenic mode.

The bed nucleus of the stria terminalis (BNST) is critically implicated in anxiety behavior and control of the hypothalamus-pituitary-adrenal axis. Having previously shown that chronic stress triggers dendritic/synaptic remodeling in specific nuclei of the BNST, we characterised the pattern of activation of neurons within different regions of the BNST under basal conditions and after an anxiogenic stimulus in control and stressed rats. Under basal conditions, stressed, but not control, animals displayed increased cFOS expression in the dorsomedial nucleus and decreased activation of the principal nucleus. This pattern resembled that observed in controls that had been exposed to the anxiogenic stimulus. Subsequent analysis of various BNST subnuclei revealed differential patterns of gene expression in controls and stressed animals. We found decreased levels of corticotropin-releasing hormone 1 receptor mRNA expression in the dorsomedial and fusiform nuclei, and a global increase in the levels of corticotropin-releasing hormone 2 receptor in the principal nucleus. In addition, we found subnuclei-specific increases in GABA(A) and NR2B receptors in stressed animals, which suggest changes in the GABAergic and glutamergic innervation of the BNST. Importantly, these findings were associated with increased anxiety-like behavior and impaired control of the hypothalamus-pituitary-adrenal axis in stressed animals. In summary, these data reveal that chronic stress shifts the pattern of response of the BNST to an anxiogenic mode and provide new information on the underlying mechanisms of the stress-induced hypercorticalism and hyperanxious status.

In vivo assessment of gastrotomy closure with over-the-scope clips in an experimental model for varicocelectomy (with video).

BACKGROUND: Gastrotomy closure remains the major limiting factor for human translation of transgastric surgery; the over-the-scope clip (OTSC) system was proposed as a possibility for this purpose. Transgastric access is good for a pelvic approach, making varicocelectomy a possible indication for natural orifice transluminal endoscopic surgery (NOTES). OBJECTIVE: To evaluate the reliability of the OTSC system in vivo after transgastric testicular vessel ligation (varicocelectomy model). DESIGN: There were 3 experimental groups (5 animals in each): groups 1 and 3, gastrotomy dilation up to 18 mm, surgery was performed with a double-channel endoscope; group 2, gastrotomy dilation up to 13 mm, surgery was performed with a single-channel endoscope. SETTING: Surgical Sciences Research Domain, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal. INTERVENTIONS: Bilateral testicular vessel ligation by transgastric access. Gastrotomy closed with the largest version of OTSC system (12 mm): a single clip in groups 1 and 2, and 2 clips in group 3. Animals were monitored for 2 weeks, killed, and submitted for necropsy. MAIN OUTCOME MEASUREMENTS: Adequacy of closure and healing after the use of the OTSC system. Statistical analysis. RESULTS: Vessel ligation was easily achieved in all groups. Although differences in the complication rate did not reach statistical significance (P = .099), there was a clear tendency for a better prognosis in groups 2 and 3 than group 1. In fact, only 2 animals from group 1 had complications related to incomplete gastrotomy closure. LIMITATIONS: Small number of animals per group; nonrandomized study. CONCLUSIONS: The OTSC system was shown to be easy and efficient for gastrotomy closure in a survival experimental model of varicocelectomy, when correctly matching the gastrotomy size with the clip size and/or number.

Antinociception induced by chronic glucocorticoid treatment is correlated to local modulation of spinal neurotransmitter content.

BACKGROUND: While acute effects of stress on pain are well described, those produced by chronic stress are still a matter of dispute. Previously we demonstrated that chronic unpredictable stress results in antinociception in the tail-flick test, an effect that is mediated by increased levels of corticosteroids. In the present study, we evaluated nociception in rats after chronic treatment with corticosterone (CORT) and dexamethasone (DEX) in order to discriminate the role of each type of corticosteroid receptors in antinociception. RESULTS: Both experimental groups exhibited a pronounced antinociceptive effect after three weeks of treatment when compared to controls (CONT); however, at four weeks the pain threshold in CORT-treated animals returned to basal levels whereas in DEX-treated rats antinociception was maintained. In order to assess if these differences are associated with altered expression of neuropeptides involved in nociceptive transmission we evaluated the density of substance P (SP), calcitonin gene-related peptide (CGRP), somatostatin (SS) and B2-gamma-aminobutiric acid receptors (GABAB2) expression in the spinal dorsal horn using light density measurements and stereological techniques. After three weeks of treatment the expression of CGRP in the superficial dorsal horn was significantly decreased in both CORT and DEX groups, while GABAB2 was significantly increased; the levels of SP for both experimental groups remained unchanged at this point. At 4 weeks, CGRP and SP are reduced in DEX-treated animals and GABAB2 unchanged, but all changes were restored to CONT levels in CORT-treated animals. The expression of SS remained unaltered throughout the experimental period. CONCLUSION: These data indicate that corticosteroids modulate nociception since chronic corticosteroid treatment alters the expression of neuropeptides involved in nociceptive transmission at the spinal cord level. As previously observed in some supraspinal areas, the exclusive GR activation resulted in more profound and sustained behavioural and neurochemical changes, than the one observed with a mixed ligand of corticosteroid receptors. These results might be of relevance for the pharmacological management of certain types of chronic pain, in which corticosteroids are used as adjuvant analgesics.

Endoscopic closure of transmural bladder wall perforations.

BACKGROUND: Traditionally, intraperitoneal bladder perforations caused by trauma or iatrogenic interventions have been treated by open or laparoscopic surgery. Additionally, transvesical access to the peritoneal cavity has been reported to be feasible and useful for natural orifice translumenal endoscopic surgery (NOTES) but would be enhanced by a reliable method of closing the vesicotomy. OBJECTIVE: To assess the feasibility and safety of an endoscopic closure method for vesical perforations using a flexible, small-diameter endoscopic suturing kit in a survival porcine model. DESIGN, SETTING, AND PARTICIPANTS: This pilot study was performed at the University of Minho, Braga, Portugal, using six anesthetized female pigs. INTERVENTIONS: Closure of a full-thickness longitudinal incision in the bladder dome (up to 10 mm in four animals and up to 20 mm in two animals) with the endoscopic suturing kit using one to three absorbable stitches. MEASUREMENTS: The acute quality of sealing was immediately tested by distending the bladder with methylene-blue dye under laparoscopic control (in two animals). Without a bladder catheter, the animals were monitored daily for 2 wk, and a necropsy examination was performed to check for the signs of peritonitis, wound dehiscence, and quality of healing. RESULTS AND LIMITATIONS: Endoscopic closure of bladder perforation was carried out easily and quickly in all animals. The laparoscopic view revealed no acute leak of methylene-blue dye after distension of the bladder. After recovery from anaesthesia, the pigs began to void normally, and no adverse event occurred. Postmortem examination revealed complete healing of vesical incision with no signs of infection or adhesions in the peritoneal cavity. No limitations have yet been studied clinically. CONCLUSIONS: This study demonstrates the feasibility and the safety of endoscopic closure of vesical perforations with an endoscopic suturing kit in a survival porcine model. This study provides support for further studies using endoscopic closure of the bladder which may lead to a new era in management of bladder rupture and adoption of the transvesical port in NOTES procedures.

Neuropathic pain is associated with depressive behaviour and induces neuroplasticity in the amygdala of the rat.

Chronic pain is associated with the development of affective disorders but the underlying mechanisms are not fully understood. Changes in brain centres implicated in both emotional and pain processing are likely to be critical in the interplay of pain control and affective emotional behaviour. In the present study, we assessed emotional behaviour and performed a structural analysis of the amygdala (AMY) in neuropathic rats after two months of hyperalgesia and allodynia, induced by the spared nerve injury model (SNI). When compared with Sham-controls, SNI animals displayed signs of depressive-like behaviour. In addition, we found an increased amygdalar volume in SNI rats. No alterations were found in the dendritic arborizations of AMY neurons but, surprisingly, the amygdalar hypertrophy was associated with an increased cell proliferation [bromodeoxyuridine (BrdU)-positive cells] in the central (CeA) and basolateral (BLA) amygdaloid nuclei. The phenotypic analysis of the newly-acquired cells revealed that they co-label for neuronal markers (BrdU+NeuN and BrdU+Calbindin), but not for differentiated glial cells (BrdU+glial fibrillary acidic protein). We demonstrate that neuropathic pain promotes generation of new neurons in the AMY. Given the established role of the AMY in emotional behaviour, we propose that these neuroplastic changes might contribute for the development of depressive-like symptoms that are usually present in prolonged pain syndromes in humans.

Third-generation nephrectomy by natural orifice transluminal endoscopic surgery.

PURPOSE: Recently there has been increasing enthusiasm for performing simple abdominal procedures by transgastric surgery. We previously reported the usefulness of a combined transgastric and transvesical approach to cholecystectomy. In this study we assessed the feasibility of combined transgastric and transvesical approach for performing a more complex surgical procedure, such as nephrectomy, in a porcine model. MATERIALS AND METHODS: In a nonsurvival study combined transgastric and transvesical approaches were established in 6 female pigs. Under ureteroscope guidance we installed a transvesical 5 mm over tube into the peritoneal cavity and a flexible gastroscope was passed orally into the peritoneal cavity by a gastrotomy. We performed right or left nephrectomy with instruments introduced by the 2 devices that worked in the renal hilum, alternating device intervention for dissection and retraction procedures. RESULTS: Four right and 2 left nephrectomies were performed. There were no complications during the creation of transvesical and transgastric access. In all animals we visualized the 2 kidneys. The renal vessels and ureter were reasonably individualized and ligated separately with ultrasonic scissors, which were introduced through the transvesical port. In 2 early cases mild hemorrhage occurred after ultrasonic ligation. To overcome this complication we applied clips successfully before ultrasonic ligation in the remaining animals. Thus, complete renal release and mobilization to the stomach were achieved in all animals. CONCLUSIONS: Nephrectomy by natural orifices using the combined transgastric and transvesical approach is technically feasible, although to our knowledge there is no reliable method for removing the specimen with current instruments.

Transvesical thoracoscopy: a natural orifice translumenal endoscopic approach for thoracic surgery.

BACKGROUND: Recently there has been an increasing enthusiasm for using natural orifices translumenal endoscopic surgery (NOTES) to perform scarless abdominal procedures. We have previously reported the feasibility and safety of the transvesical endoscopic peritoneoscopy in a long-term survival porcine model as useful for those purposes. Herein, we report our successful experience performing transvesical and transdiaphragmatic endoscopic approach to the thoracic cavity in a long-term survival study in a porcine model. METHODS: Transvesical and transdiaphragmatic endoscopic thoracoscopy was performed in six anesthetized female pigs. A 5 mm transvesical port was created on the bladder wall and an ureteroscope was advanced into the peritoneal cavity. After diaphragm inspection, we introduced through the left diaphragmatic dome a ureteroscope into the left thoracic cavity. In all animals, we performed thoracoscopy as well as peripheral lung biopsy. Animals were sacrificed by day 15 postoperatively. RESULTS: We easily introduced a 9.8 Fr ureteroscope into the thoracic cavity that allowed us to visualize the pleural cavity and to perform simple surgical procedures such as lung biopsies without complications. There were neither respiratory distress episodes nor surgical complications to report. Postmortem examination revealed complete healing of vesical and diaphragmatic holes, whereas no signs of infection or adhesions were observed in the peritoneal or thoracic cavities. CONCLUSION: This study demonstrates the feasibility of transvesical thoracoscopy in porcine model. However, although this study extends the potential applications of NOTES to the thoracic cavity, new instruments and further work are needed to provide evidence that this could be translated to humans and with advantages for patients.