Real-time activity-dependent drug microinjection

From Eighteenth Annual Computational Neuroscience Meeting: CNS*2009 Berlin, Germany. 18–23 July 2009This work was supported by MEC PHB2007-0013TA, BFU2006-07902/BFI, TIN 2007-65989, CAM S-SEM-0255-2006. RDP was supported by the Brazilian agencies: CAPES, CNPq and FAPESP

Neural Mechanisms Underlying the Generation of the Lobster Gastric Mill Motor Pattern

The lobster gastric mill central pattern generator (CPG) is located in the stomatogastric ganglion and consists of 11 neurons whose circuitry is well known. Because all of the neurons are identifiable and accessible, it can serve as a prime experimental model for analyzing how microcircuits generate multiphase oscillatory spatiotemporal patterns. The neurons that comprise the gastric mill CPG consist of one interneuron, five burster neurons and six tonically firing neurons. The single interneuron (Int 1) is shared by the medial tooth subcircuit (containing the AM, DG and GMs) and the lateral teeth subcircuit (LG, MG and LPGs). By surveying cell-to-cell connections and the cooperative dynamics of the neurons we find that the medial subcircuit is essentially a feed forward system of oscillators. The Int 1 neuron entrains the DG and AM cells by delayed excitation and this pair then periodically inhibits the tonically firing GMs causing them to burst. The lateral subcircuit consists of two negative feedback loops of reciprocal inhibition from Int 1 to the LG/MG pair and from the LG/MG to the LPGs. Following a fast inhibition from Int 1, the LG/MG neurons receive a slowly developing excitatory input similar to that which Int 1 puts onto DG/AM. Thus Int 1 plays a key role in synchronizing both subcircuits. This coordinating role is assisted by additional, weaker connections between the two subsets but those are not sufficient to synchronize them in the absence of Int 1. In addition to the experiments, we developed a conductance-based model of a slightly simplified gastric circuit. The mathematical model can reproduce the fundamental rhythm and many of the experimentally induced perturbations. Our findings shed light on the functional role of every cell and synapse in this small circuit providing a detailed understanding of the rhythm generation and pattern formation in the gastric mill network

Temporal code-driven stimulation: definition and application to electric fish signaling

This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permissionClosed-loop activity-dependent stimulation is a powerful methodology to assess information processing in biological systems. In this context, the development of novel protocols, their implementation in bioinformatics toolboxes and their application to different description levels open up a wide range of possibilities in the study of biological systems. We developed a methodology for studying biological signals representing them as temporal sequences of binary events. A specific sequence of these events (code) is chosen to deliver a predefined stimulation in a closed-loop manner. The response to this code-driven stimulation can be used to characterize the system. This methodology was implemented in a real time toolbox and tested in the context of electric fish signaling. We show that while there are codes that evoke a response that cannot be distinguished from a control recording without stimulation, other codes evoke a characteristic distinct response. We also compare the code-driven response to open-loop stimulation. The discussed experiments validate the proposed methodology and the software toolbox.This work was funded by Spanish projects of Ministerio de Economia y Competitividad/FEDER TIN-2010-19607, TIN2014-54580-R, TIN-2012-30883, DPI2015 65833-P (http://www.mineco.gob.es/), ONRG grant N62909-14-1-N279, Brazilian Agency of Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (http://www.cnpq.br/) and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (www.fapesp.br). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Online video tracking for activity-dependent stimulation in neuroethology

Poster presentation from Twentieth Annual Computational Neuroscience Meeting: CNS*2011. Stockholm, Sweden. 23-28 July 2011This work was supported by grants MICINN BFU2009-08473 and TIN 2010- 19607, Spanish-Brazilian Cooperation PHB2007-0008 and Brazilian agencies FAPESP, CNPq and CAPES

StdpC: a modern dynamic clamp

With the advancement of computer technology many novel uses of dynamic clamp have become possible. We have added new features to our dynamic clamp software StdpC (“Spike timing-dependent plasticity Clamp”) allowing such new applications while conserving the ease of use and installation of the popular earlier Dynclamp 2/4 package. Here, we introduce the new features of a waveform generator, freely programmable Hodgkin–Huxley conductances, learning synapses, graphic data displays, and a powerful scripting mechanism and discuss examples of experiments using these features. In the first example we built and ‘voltage clamped’ a conductance based model cell from a passive resistor–capacitor (RC) circuit using the dynamic clamp software to generate the voltage-dependent currents. In the second example we coupled our new spike generator through a burst detection/burst generation mechanism in a phase-dependent way to a neuron in a central pattern generator and dissected the subtle interaction between neurons, which seems to implement an information transfer through intraburst spike patterns. In the third example, making use of the new plasticity mechanism for simulated synapses, we analyzed the effect of spike timing-dependent plasticity (STDP) on synchronization revealing considerable enhancement of the entrainment of a post-synaptic neuron by a periodic spike train. These examples illustrate that with modern dynamic clamp software like StdpC, the dynamic clamp has developed beyond the mere introduction of artificial synapses or ionic conductances into neurons to a universal research tool, which might well become a standard instrument of modern electrophysiology

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)