Volume-Conducted Origin of the Field Potential at the Lateral Habenula

Field potentials (FPs) are easily reached signals that provide information about the brain’s processing. However, FP should be interpreted cautiously since their biophysical bases are complex. The lateral habenula (LHb) is a brain structure involved in the encoding of aversive motivational values. Previous work indicates that the activity of the LHb is relevant for hippocampal-dependent learning. Moreover, it has been proposed that the interaction of the LHb with the hippocampal network is evidenced by the synchronization of LHb and hippocampal FPs during theta rhythm. However, the origin of the habenular FP has not been analyzed. Hence, its validity as a measurement of LHb activity has not been proven. In this work, we used electrophysiological recordings in anesthetized rats and feed-forward modeling to investigate biophysical basis of the FP recorded in the LHb. Our results indicate that the FP in the LHb during theta rhythm is a volume-conducted signal from the hippocampus. This result highlight that FPs must be thoroughly analyzed before its biological interpretation and argues against the use of the habenular FP signal as a readout of the activity of the LHb.Fil: Bertone Cueto, Nicolas Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Makarova, Julia. Consejo Superior de Investigaciones Científicas; EspañaFil: Mosqueira, Alejo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: García Violini, Demian. Instituto Tecnológico de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sanchez Peña, Ricardo Salvador. Instituto Tecnológico de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Herreras, Oscar. Consejo Superior de Investigaciones Científicas; EspañaFil: Belluscio, Mariano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Piriz, Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

Biomasa radical de pastos bajo labranza y fertilización en un inceptisol del valle del Sinú

Angleton grass (Dicanthium aristatum) is the dominant Gramineae specie in the Sinu River Valley. Its root growth is limited by soil compaction, a mixed effect of high density and penetration resistance. With the aim to determine the effect of vertical tillage and fertilization over root biomass, soil density and penetration resistance, four different kinds of grasses (Mulato II, Toledo, Angleton and Estrella) were established on an inceptisol soil located at Turipaná Research Center, in Cereté, Córdoba, Colombia. Four vertical tillage treatments with three repeats were evaluated: two with rigid chisel, 30 cm - 60 cm and two with grassland renovator, horizontal distance 30 and 60 cm, and 30 cm depth. Two levels of fertilization were evaluated: F1: 300 kg ha-1 of DAP (18% N - 46% P2 O5 ), 200 kg ha-1 of KCl (60% K2 O) and 150 kg ha-1 of urea (46% N) and F2 : 50% of the previous described treatment. In a split plot design experiment, the effect of vertical tillage and fertilization during 18 months over soil density, penetration resistance and root biomass growth were tested by ANOVA and average Duncan comparison. No independent effect of tillage or fertilization on grasses was observed, but there are significant interaction between tillage and grasses, fertilization and grasses and tillagefertilization and grasses. It is concluded that differences in the variables soil density, penetration resistance and root biomass were due to grazing effect and tillage-fertilization-grass interaction.La biomasa radical de los pastos predominantes en el Valle del río Sinú está limitada por la compactación del suelo, caracterizada por la alta densidad y resistencia a la penetración. Con el propósito de determinar el efecto de la labranza vertical y fertilización sobre la biomasa radical, densidad del suelo y resistencia a la penetración, se establecieron los pastos Mulato II, Toledo, Ángleton y Estrella en un inceptisol del Centro de Investigación Turipaná, ubicado en Cereté, Córdoba, Colombia; bajo un diseño de parcelas subdivididas con tres repeticiones. Los tratamientos fueron cuatro sistemas de labranza vertical (dos con cincel rígido a 30 y 60 cm y dos con renovador de praderas a 30 y 60 cm de distancia horizontal, ambas a 30 cm de profundidad) y dos niveles de fertilización (F1= 300 kg ha-1 de DAP (18% N - 46% P2O5), 200 kg ha-1 de KCl (60% K2O) y 150 kg ha-1 de úrea (46% N) y F2 = 50% de las dosis anteriores. Los resultados a los 18 meses después de aplicado los tratamientos no mostraron efecto de la labranza ni de la fertilización en los pastos; mas sí hubo interacciones significativas entre labranza y pastos, fertilización y pastos, labranza - fertilización y pastos. Se concluye que las diferencias en las variables densidad del suelo, resistencia a la penetración y biomasa radical se encontraron por efecto de los pastos y por la interacción labranza - fertilización - pasto

A crowdsourcing database for the copy-number variation of the Spanish population

Background: Despite being a very common type of genetic variation, the distribution of copy-number variations (CNVs) in the population is still poorly understood. The knowledge of the genetic variability, especially at the level of the local population, is a critical factor for distinguishing pathogenic from non-pathogenic variation in the discovery of new disease variants. Results: Here, we present the SPAnish Copy Number Alterations Collaborative Server (SPACNACS), which currently contains copy number variation profiles obtained from more than 400 genomes and exomes of unrelated Spanish individuals. By means of a collaborative crowdsourcing effort whole genome and whole exome sequencing data, produced by local genomic projects and for other purposes, is continuously collected. Once checked both, the Spanish ancestry and the lack of kinship with other individuals in the SPACNACS, the CNVs are inferred for these sequences and they are used to populate the database. A web interface allows querying the database with different filters that include ICD10 upper categories. This allows discarding samples from the disease under study and obtaining pseudo-control CNV profiles from the local population. We also show here additional studies on the local impact of CNVs in some phenotypes and on pharmacogenomic variants. SPACNACS can be accessed at: http://csvs.clinbioinfosspa.es/spacnacs/. Conclusion: SPACNACS facilitates disease gene discovery by providing detailed information of the local variability of the population and exemplifies how to reuse genomic data produced for other purposes to build a local reference database

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Classification based on dynamic mode decomposition applied to brain recognition of context

Local Field Potentials (LFPs) are easy to access electrical signals of the brain that represent the summation in the extracellular space, of currents originated within the neurons. As such, LFPs could contain information about ongoing computations in neuronal circuits and could potentially be used to design brain machine interface algorithms. However how brain computations could be decoded from LFPs is not clear. Within this context, a methodology for signal classification is proposed in this study, particularly based on the Dynamic Mode Decomposition method, in conjunction with binary clustering routines based on supervised learning. Note that, although the classification methodology is presented here in the context of a biological problem, it can be applied to a broad range of applications. Then, as a case-study, the proposed method is validated with the classification of LFP-based brain cognitive states. All the analysis, signals, and results shown in this study consider real data measured in the hippocampus, in rats performing exploration tasks. Consequently, it is shown that, using the measured LFP, the method infers which context was the animal exploring. Thus, evidence on the spatial codification in LFP signals is consequently provided, which still is an open question in neuroscience.Fil: Martínez, Sebastián. Instituto Tecnológico de Buenos Aires; ArgentinaFil: Silva, Azul. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: García Violini, Diego Demián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Piriz, Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Belluscio, Mariano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Sanchez Peña, Ricardo Salvador. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Tecnológico de Buenos Aires; Argentin

Volume-Conducted Origin of the Field Potential at the Lateral Habenula

Field potentials (FPs) are easily reached signals that provide information about the brain’s processing. However, FP should be interpreted cautiously since their biophysical bases are complex. The lateral habenula (LHb) is a brain structure involved in the encoding of aversive motivational values. Previous work indicates that the activity of the LHb is relevant for hippocampal-dependent learning. Moreover, it has been proposed that the interaction of the LHb with the hippocampal network is evidenced by the synchronization of LHb and hippocampal FPs during theta rhythm. However, the origin of the habenular FP has not been analyzed. Hence, its validity as a measurement of LHb activity has not been proven. In this work, we used electrophysiological recordings in anesthetized rats and feed-forward modeling to investigate biophysical basis of the FP recorded in the LHb. Our results indicate that the FP in the LHb during theta rhythm is a volume-conducted signal from the hippocampus. This result highlight that FPs must be thoroughly analyzed before its biological interpretation and argues against the use of the habenular FP signal as a readout of the activity of the LHb.This work was supported by the following grants: NARSAD Young Investigator Award 2015 (#23861) from the Brain and Behavior Foundation; PICT 2015-2609 and PICT 2017-4594 from the National Agency for Scientific and Technological Promotion of Argentina (ANPCyT) to JP; PICT 2016-0396 from the ANPCyT; UBACYT 2018 from the Universidad de Buenos Aires to MB; SAF2016-80100-R from the Spanish Ministry of Economy and Competitiveness to OH and JM; PICT 2017-2417 from the ANPCyT to RS-P. NB-C and DG-V were supported by predoctoral and postdoctoral fellowships from the CONICET, respectively