Convergent evolution of sodium ion selectivity in metazoan neuronal signaling

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Cell Reports 2 (2012): 242–248, doi:10.1016/j.celrep.2012.06.016.Ion selectivity of metazoan voltage-gated Na+ channels is critical for neuronal signaling and has long been attributed to a ring of four conserved amino acids that constitute the ion selectivity filter (SF) at the channel pore. Yet, in addition to channels with a preference for Ca2+ ions, the expression and characterization of Na+ channel homologs from the sea anemone Nematostella vectensis, a member of the early-branching metazoan phylum Cnidaria, revealed a sodium-selective channel bearing a noncanonical SF. Mutagenesis and physiological assays suggest that pore elements additional to the SF determine the preference for Na+ in this channel. Phylogenetic analysis assigns the Nematostella Na+-selective channel to a channel group unique to Cnidaria, which diverged >540 million years ago from Ca2+-conducting Na+ channel homologs. The identification of Cnidarian Na+-selective ion channels distinct from the channels of bilaterian animals indicates that selectivity for Na+ in neuronal signaling emerged independently in these two animal lineages.This study was supported by a research grant from the Austrian National Science Foundation (FWF P 21108-B17) to U.T., and by a United States-Israel Binational Agricultural Research and Development Grant (IS-4313-10) and an Israeli Science Foundation grant (107/08) to M.G

Rapid development of interprofessional in situ simulation-based training in response to the COVID-19 outbreak in a tertiary-level hospital in Ireland:Initial response and lessons for future disaster preparation.

INTRODUCTION: The first case of COVID-19 in Ireland was diagnosed on 29 February 2020. Within the same week, our Department of Anaesthesia and Critical Care at University Hospital Galway began to tackle the educational challenge by developing an  in situ interprofessional simulation programme to prepare staff for the impending outbreak. PRINCIPLES AND APPROACHES USED FOR SIMULATION-BASED TRAINING: We describe principles applied to identify core educational and system engineering objectives to prepare healthcare workers (HCWs) for infection control, personal and psychological safety, technical and crisis resource management skills. We discuss application of educational theories, rationale for simulation modes and debriefing techniques. DEVELOPMENT OF THE SIMULATION PROGRAMME: 3 anaesthesia (general, obstetric, paediatric) and 1 critical care silo were created. 13 simulated scenarios were developed for teaching as well as for testing workflows specific to the outbreak. To support HCWs and ensure safety, management guidelines, cognitive aids and checklists were developed using simulation. The cumulative number of HCWs trained in simulation was 750 over a 4-week period. CHALLENGES AND FUTURE DIRECTIONS: Due to the protracted nature of the pandemic, simulation educators should address questions related to sustainability, infection control while delivering simulation, establishment of hybrid programmes and support for psychological preparedness

Neurociencia y su aporte determinante en la educación

The use of pedagogical techniques and methods becomes increasingly essential and more interesting to achieve the desired meaningful learning, a process that encompasses the emotional, motivational and cognitive dimension of the student. In this type of learning, as is known, prior knowledge is used to acquire other knowledge and reaffirm it in the new cognitive structure. However, sometimes it is forgotten that meaningful learning is a process that encompasses the emotional, motivational and cognitive dimensions of the person. It is correct, in the current educational paradigm, for the teacher to advise his students and guide them in the use of the technology that the era of communication and knowledge makes available to them; However, neither teachers nor students should ignore knowing how neurobiological processes intervene in learning, in order to design better educational methods and policies. Research on Neuroscience has gained more and more interest in the teaching world, given that this discipline allows us to elucidate how the brain learns, remembers and forgets; very important processes in teaching-learning. The objective of this work is to confirm that the functioning of the nervous system and, especially, the brain, play a relevant role in the acquisition of new knowledge. In order to understand this entire process, it was determined that this research must apply the Deductive-Inductive method, since the type of research is Mixed.Cada vez se hace imprescindible y más interesante el uso de técnicas y métodos pedagógicos para alcanzar el anhelado aprendizaje significativo, proceso que engloba la dimensión emocional, motivacional y cognitiva del estudiante. En este tipo de aprendizaje, como es conocido, se utilizan los conocimientos previos para adquirir otros conocimientos y reafirmarlos en la nueva estructura cognitiva. Sin embargo, a veces se olvida que el aprendizaje significativo es un proceso que engloba la dimensión emocional, motivacional y cognitiva de la persona. Es correcto, en el actual paradigma educativo, que el docente asesore a sus alumnos y los oriente en el uso de la tecnología que la era de la comunicación y el conocimiento pone a su disposición; sin embargo, docentes ni estudiantes deben abstraerse de conocer cómo intervienen los procesos neurobiológicos en el aprendizaje, para poder diseñar mejores métodos y políticas educativas. La investigación sobre la Neurociencia ha cobrado cada vez más interés en el mundo docente, dado que esta disciplina permite dilucidar de qué manera aprende, recuerda y olvida el cerebro; procesos muy importantes en la enseñanza- aprendizaje. El presente trabajo tiene como objetivo confirmar que el funcionamiento del sistema nervioso y, en especial del cerebro, juegan un papel relevante en la adquisición de nuevos conocimientos. Para poder entender todo este proceso se determinó que la presente investigación debe aplicar el método Deductivo-Inductivo, pues el tipo de investigación es Mixto

Membranes by the Numbers

Many of the most important processes in cells take place on and across membranes. With the rise of an impressive array of powerful quantitative methods for characterizing these membranes, it is an opportune time to reflect on the structure and function of membranes from the point of view of biological numeracy. To that end, in this article, I review the quantitative parameters that characterize the mechanical, electrical and transport properties of membranes and carry out a number of corresponding order of magnitude estimates that help us understand the values of those parameters.Comment: 27 pages, 12 figure

Clinical outcomes of COVID-19 and influenza in hospitalized children <5 years in the US

IntroductionWe compared hospitalization outcomes of young children hospitalized with COVID-19 to those hospitalized with influenza in the United States.MethodsPatients aged 0-&lt;5 years hospitalized with an admission diagnosis of acute COVID-19 (April 2021-March 2022) or influenza (April 2019-March 2020) were selected from the PINC AI Healthcare Database Special Release. Hospitalization outcomes included length of stay (LOS), intensive care unit (ICU) admission, oxygen supplementation, and mechanical ventilation (MV). Inverse probability of treatment weighting was used to adjust for confounders in logistic regression analyses.ResultsAmong children hospitalized with COVID-19 (n = 4,839; median age: 0 years), 21.3% had an ICU admission, 19.6% received oxygen supplementation, 7.9% received MV support, and 0.5% died. Among children hospitalized with influenza (n = 4,349; median age: 1 year), 17.4% were admitted to the ICU, 26.7% received oxygen supplementation, 7.6% received MV support, and 0.3% died. Compared to children hospitalized with influenza, those with COVID-19 were more likely to have an ICU admission (adjusted odds ratio [aOR]: 1.34; 95% confidence interval [CI]: 1.21–1.48). However, children with COVID-19 were less likely to receive oxygen supplementation (aOR: 0.71; 95% CI: 0.64–0.78), have a prolonged LOS (aOR: 0.81; 95% CI: 0.75–0.88), or a prolonged ICU stay (aOR: 0.56; 95% CI: 0.46–0.68). The likelihood of receiving MV was similar (aOR: 0.94; 95% CI: 0.81, 1.1).ConclusionsHospitalized children with either SARS-CoV-2 or influenza had severe complications including ICU admission and oxygen supplementation. Nearly 10% received MV support. Both SARS-CoV-2 and influenza have the potential to cause severe illness in young children

Prevalence and clinical impact of endoscopic pseudomembranes in patients with inflammatory bowel disease and Clostridium difficile infection

Background and aim: Limited data suggests that pseudomembranes are uncommon in patients with inflammatory bowel disease (IBD) and C. difficile associated disease (CDAD), but the reason for this is unknown. We aimed to evaluate the rate of pseudomembranes in this population, identify predictive factors for pseudomembranes' presence and assess its clinical impact. Methods: This was a sub-study of a retrospective European Crohn's & Colitis Organization (ECCO) multi-center study on the outcome of hospitalized IBD patients with C. difficile. The present study included only patients who underwent lower endoscopy during hospitalization, and compared demographic and clinical parameters in the group of patients with discernable pseudomembranes versus those without. Results: Out of 155 patients in the original cohort, 93 patients underwent lower endoscopy and constituted the study population. Endoscopic pseudomembranes were found in 12 (13%) of these patients. Patients with pseudomembranes presented more commonly with fever (p=0.02) compared to patients without pseudomembranes. No difference between the two groups was found with respect to the use of immunosuppressant drugs, background demographics or disease characteristics. Neither was there a difference between the group with or without pseudomembranes in the frequency of severe adverse clinical outcome or in the duration of hospitalization. On multi-variate analysis the presence of fever remained independently associated with the finding of pseudomembranes (OR 6, 95% CI 1.2–32, p=0.03). Conclusions: This study documents that hospitalized IBD patients with CDAD have low rate of endoscopic pseudomembranes, which is not accounted for by the use of immunosuppressant drugs. IBD patients with CDAD and discernable pseudomembranes more commonly present with fever, but their clinical outcome is similar to patients without pseudomembranes. © 2009 Published by Elsevier B.V. on behalf of European Crohn's and Colitis Organisation

Brain Diffusivity in Infants With Hypoxic-Ischemic Encephalopathy Following Whole Body Hypothermia: Preliminary Results

Abstract Hypoxic-ischemic encephalopathy is an important cause of neuropsychological deficits. Little is known about brain diffusivity in these infants following cooling and its potential in predicting outcome. Diffusion tensor imaging was applied to 3 groups: (1) three infants with hypoxic-ischemic encephalopathy: cooled; (2) three infants with hypoxic-ischemic encephalopathy: noncooled; and (3) four controls. Diffusivity values at the corticospinal tract, thalamus, and putamen were correlated with Apgar scores and early neurodevelopmental outcome. While cooled infants exhibited lower Apgar scores than noncooled infants, their developmental scores at a mean age of 8 months were higher. All groups differed in their diffusivity values with the cooled infants showing better values compared with the noncooled, correlating with early neurodevelopmental outcome. These preliminary results indicate that diffusion tensor imaging performed at an early age in infants with hypoxic-ischemic encephalopathy may forecast clinical outcome and support the neuroprotective effect of hypothermia treatment

Restoring brain function after stroke - bridging the gap between animals and humans

Stroke is the leading cause of complex adult disability in the world. Recovery from stroke is often incomplete, which leaves many people dependent on others for their care. The improvement of long-term outcomes should, therefore, be a clinical and research priority. As a result of advances in our understanding of the biological mechanisms involved in recovery and repair after stroke, therapeutic opportunities to promote recovery through manipulation of poststroke plasticity have never been greater. This work has almost exclusively been carried out in preclinical animal models of stroke with little translation into human studies. The challenge ahead is to develop a mechanistic understanding of recovery from stroke in humans. Advances in neuroimaging techniques now enable us to reconcile behavioural accounts of recovery with molecular and cellular changes. Consequently, clinical trials can be designed in a stratified manner that takes into account when an intervention should be delivered and who is most likely to benefit. This approach is expected to lead to a substantial change in how restorative therapeutic strategies are delivered in patients after stroke

Extent, intensity and drivers of mammal defaunation:a continental-scale analysis across the Neotropics

Neotropical mammal diversity is currently threatened by several chronic human-induced pressures. We compiled 1,029 contemporary mammal assemblages surveyed across the Neotropics to quantify the continental-scale extent and intensity of defaunation and understand their determinants based on environmental covariates. We calculated a local defaunation index for all assemblages—adjusted by a false-absence ratio—which was examined using structural equation models. We propose a hunting index based on socioenvironmental co-variables that either intensify or inhibit hunting, which we used as an additional predictor of defaunation. Mammal defaunation intensity across the Neotropics on average erased 56.5% of the local source fauna, with ungulates comprising the most ubiquitous losses. The extent of defaunation is widespread, but more incipient in hitherto relatively intact major biomes that are rapidly succumbing to encroaching deforestation frontiers. Assemblage-wide mammal body mass distribution was greatly reduced from a historical 95th-percentile of ~ 14 kg to only ~ 4 kg in modern assemblages. Defaunation and depletion of large-bodied species were primarily driven by hunting pressure and remaining habitat area. Our findings can inform guidelines to design transnational conservation policies to safeguard native vertebrates, and ensure that the “empty ecosystem” syndrome will be deterred from reaching much of the New World tropics