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

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

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

The development and implementation of a computer adaptive progress test across European countries

Longitudinal progress testing promotes self-directed deep learning across a full spectrum of knowledge, enabling early detection of underperformance and opportunities for remediation. Computer adaptive testing (CAT), where the difficulty of a test dynamically adjusts according to a test taker's ability, has benefits in a progress testing context, but significant resource and experience is required to develop appropriate test materials. This study describes how a transnational consortium from eight medical schools in five countries across Europe was formed to develop a computer adaptive progress test applicable across international curricula. 1,212 students from more than 40 nationalities took part in the study, of whom more than 70% were not native English speakers, though nearly all reported competence in English. A content map for an international assessment blueprint was agreed and a substantial bank of 1,127 English language progress test items was successfully calibrated after pilot testing to form the computer adaptive progress test (CA-PT) item bank. Results from the CA-PT pilot showed reliable convergence to stable estimates of ability, low standard errors of measurement and high test reliability for all participants. This study shows that an international collaborative consortium approach enables effective development of progress testing resources appropriate for computer adaptive testing, with potential for application across international borders and in populations where English is not the native language. Pooling resources internationally facilitates the comparison and development of appropriate assessment blueprints and the efficient generation of high-quality assessment items

Third-generation cholecystectomy by natural orifices: transgastric and transvesical combined approach (with video)

BACKGROUND:An isolated transgastric port has some limitations in performing transluminal endoscopic cholecystectomy. However, transvesical access to the peritoneal cavity has recently been reported to be feasible and safe.OBJECTIVE:To assess the feasibility and the technical benefits of transgastric and transvesical combined approach to overcome the limitations of isolated transgastric ports.DESIGN:We created a transgastric and transvesical combined approach to perform cholecystectomy in 7 consecutive anesthetized female pigs. The transgastric access was achieved after perforation and dilation of the gastric wall with a needle knife and with a balloon, respectively. Under cystoscopic control, an ureteral catheter, a guidewire, and a dilator of the ureteral sheath were used to place a transvesical 5-mm overtube into the peritoneal cavity. By using a gastroscope positioned transgastrically and a ureteroscope positioned transvesically, we carried out cholecystectomy in all animals.RESULTS:Establishment of transvesical and transgastric accesses took place without complications. Under a carbon dioxide pneumoperitoneum controlled by the transvesical port, gallbladder identification, cystic duct, and artery exposure were easily achieved in all cases. Transvesical gallbladder grasping and manipulation proved to be particularly valuable to enhance gastroscope-guided dissection. With the exclusion of 2 cases where mild liver-surface hemorrhage and bile leak secondary to the sliding of cystic clips occurred, all remaining cholecystectomies were carried out without incidents.LIMITATIONS:Once closure of the gastric hole proved to be unreliable when using endoclips, the animals were euthanized; necropsy was performed immediately after the surgical procedure.CONCLUSIONS:A transgastric and transvesical combined approach is feasible, and it was particularly useful to perform a cholecystectomy through exclusive natural orifices

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.Financial support and sponsorship by CEiiA, INOV4COVID program, donations from scientific patronage, and commercial sales

Stress-induced anhedonia is associated with hypertrophy of medium spiny neurons of the nucleus accumbens

There is accumulating evidence that the nucleus accumbens (NAc) has an important role in the pathophysiology of depression. As the NAc is a key component in the neural circuitry of reward, it has been hypothesized that anhedonia, a core symptom of depression, might be related to dysfunction of this brain region. Neuronal morphology and expression of plasticity-related molecules were examined in the NAc of rats displaying anhedonic behavior (measured in the sucrose-consumption test) in response to chronic mild stress. To demonstrate the relevance of our measurements to depression, we tested whether the observed changes were sensitive to reversal with antidepressants (imipramine and fluoxetine). Data show that animals displaying anhedonic behavior display an hypertrophy of medium spiny neurons in the NAc and, in parallel, have increased expression of the genes encoding for brain-derived neurotrophic factor, neural cell adhesion molecule and synaptic protein synapsin 1. Importantly, the reversal of stress-induced anhedonia by antidepressants is linked to a restoration of gene-expression patterns and dendritic morphology in the NAc. Using an animal model of depression, we show that stress induces anhedonic behavior that is associated with specific changes in the neuronal morphology and in the gene-expression profile of the NAc that are effectively reversed after treatment with antidepressants.The present work was funded by the Portuguese Foundation for Technology (FCT), project PTDC/SAU-NEU/105180/2008. FM and PL are recipients of postdoctoral fellowships and MM is recipient of a doctoral fellowship, all from FCT, Portugal

The positive effect on ketamine as a priming adjuvant in antidepressant treatment.

Ketamine is an anesthetic with antidepressant properties. The rapid and lasting effect of ketamine observed in preclinical and clinical research makes it a promising therapeutic to improve current major depression (MD) treatment. Our work intended to evaluate whether the combined use of classic antidepressants (imipramine or fluoxetine) and ketamine would improve the antidepressant response. Using an animal model of depressive-like behavior, we show that the addition of ketamine to antidepressants anticipates the behavioral response and accelerates the neuroplastic events when compared with the use of antidepressants alone. In conclusion, our results suggest the need for a reappraisal of the current pharmacological treatment of MD.This work is supported by the Fundação para a Ciência e Tecnologia (FCT) grant SFRH/SINTD/60126/200

The bed nucleus of stria terminalis and the amygdala as targets of antenatal glucocorticoids: implications for fear and anxiety responses

Rationale: Several human and experimental studies have shown that early life adverse events can shape physical and mental health in adulthood. Stress or elevated levels of glucocorticoids (GCs) during critical periods of development seem to contribute for the appearance of neurospyschiatric conditions such as anxiety and depression, albeit the underlying mechanisms remain to be fully elucidated. Objectives: The aim of the present study was to determine the long-term effect of prenatal erxposure to dexamethasone- DEX (synthetic GC widely used in clinics) in fear and anxious behavior and identify the neurochemical, morphological and molecular correlates. Results: Prenatal exposure to DEX triggers a hyperanxious phenotype and altered fear behavior in adulthood. These behavioral traits were correlated with increased volume of the bed nucleus of the stria terminalis (BNST), particularly the anteromedial subivision which presented increased dendritic length; in parallel, we found an increased expression of synapsin and NCAM in the BNST of these animals. Remarkably, DEX effects were opposite in the amygdala, as this region presented reduced volume due to significant dendritic atrophy. Albeit no differences were found in dopamine and its metabolite levels in the BNST, this neurotransmitter was substantially reduced in the amygdala, which also presented an up-regulation of dopamine receptor 2. Conclusions: Altogether our results show that in utero DEX exposure can modulate anxiety and fear behavior in parallel with significant morphological, neurochemical and molecular changes; importantly, GCs seem to differentially affect distinct brain regions involved in this type of behaviors.This study was supported by a grant from the Institute for the Study of Affective Neuroscience (ISAN). AJR is supported by a Fundação para a Ciência e Tecnologia (FCT) grant

A Key Role for Neurotensin in Chronic-Stress-Induced Anxiety-Like Behavior in Rats

Accepted ManuscriptChronic stress is a major cause of anxiety disorders that can be reliably modeled preclinically, providing insight into alternative therapeutic targets for this mental health illness. Neuropeptides have been targeted in the past to no avail possibly due to our lack of understanding of their role in pathological models. In this study we use a rat model of chronic stress-induced anxiety-like behaviors and hypothesized that neuropeptidergic modulation of synaptic transmission would be altered in the bed nucleus of the stria terminalis (BNST), a brain region suspected to contribute to anxiety disorders. We use brain slice neurophysiology and behavioral pharmacology to compare the role of locally released endogenous neuropeptides on synaptic transmission in the oval (ov) BNST of non-stressed (NS) or chronic unpredictably stressed (CUS) rats. We found that in NS rats, post-synaptic depolarization induced the release of vesicular neurotensin (NT) and corticotropin-releasing factor (CRF) that co-acted to increase ovBNST inhibitory synaptic transmission in 59% of recorded neurons. CUS bolstered this potentiation (100% of recorded neurons) through an enhanced contribution of NT over CRF. In contrast, locally released opioid neuropeptides decreased ovBNST excitatory synaptic transmission in all recorded neurons, regardless of stress. Consistent with CUS-induced enhanced modulatory effects of NT, blockade of ovBNST NT receptors completely abolished stress-induced anxiety-like behaviors in the elevated plus maze paradigm. The role of NT has been largely unexplored in stress and our findings highlight its potential contribution to an important behavioral consequence of chronic stress, that is, exaggerated avoidance of open space in rats.CPN was funded by CIHR Vanier Graduate Scholarship (338319); APVS was funded by Fundação para a Ciência e Tecnologia (SFRH/BPD/52078/2013); ERH was funded by CIHR Postdoctoral Fellowship (MFE-123712); SA was funded by a Queen Elizabeth II Graduate Scholarship in Science and Technology; ÉCD was funded by the Canadian Institute of Health Research (MOP-25953)info:eu-repo/semantics/publishedVersio

Differential impact of chronic stress along the hippocampal dorsal–ventral axis

First published online 06 February 2014Stress impacts differently in distinct brain regions. However, so far few studies have focused on the differential responses triggered by stressful stimuli on the intrinsic functional heterogeneity of the hippocampal axis. In this study, we assessed the functional and structural alterations caused by exposure to a chronic unpredictable stress (CUS) paradigm on the dorsal-ventral axis of the hippocampus. The morphological analysis demonstrated that CUS had opposite outcomes in the structure of the dorsal (DH) and ventral hippocampus (VH): whereas in the DH, stress triggered a volumetric reduction as a result of atrophy of CA3 and CA1 apical dendrites, in the VH there was an increase in hippocampal volume concurrent with the increase of CA3 apical dendrites. In parallel, electrophysiological data revealed that stress led to a decrease in VH LTD. In summary, the present work showed that stress impacts differently on the structure and function of the DH and VH which contributes to better understand the overall spectrum of the central effects of stress.Pinto V and Mota C were supported by Fundacao para a Ciencia e Tecnologia (FCT) grants (SFRH/BPD/69132/2010; SFRH/BD/81881/2011, respectively). This work was supported by an FCT grant (PTDC/SAU-NSC/120590/2010). The authors declare no competing financial interests