Large-scale, high-resolution electrophysiological imaging of field potentials in brain slices with microelectronic multielectrode arrays

Multielectrode arrays (MEAs) are extensively used for electrophysiological studies on brain slices, but the spatial resolution and field of recording of conventional arrays are limited by the low number of electrodes available. Here, we present a large-scale array recording simultaneously from 4096 electrodes used to study propagating spontaneous and evoked network activity in acute murine cortico-hippocampal brain slices at unprecedented spatial and temporal resolution. We demonstrate that multiple chemically induced epileptiform episodes in the mouse cortex and hippocampus can be classified according to their spatio-temporal dynamics. Additionally, the large-scale and high-density features of our recording system enable the topological localization and quantification of the effects of antiepileptic drugs in local neuronal microcircuits, based on the distinct field potential propagation patterns. This novel high-resolution approach paves the way to detailed electrophysiological studies in brain circuits spanning spatial scales from single neurons up to the entire slice network

Contando pobres : Entre las estadísticas oficiales y el saber especifico

Advirtiendo el lugar central que ocupa el estudio de la pobreza en el ámbito de las decisiones políticas, el siguiente trabajo reflexiona sobre dos dimensiones vinculantes y profundamente significativas para la planificación y desarrollo de un país: la pobreza y las estadísticas oficiales. En esta dirección se realiza un breve recorrido por los diferentes enfoques que el estudio de la pobreza asume en las estadísticas oficiales atendiendo, tanto a los antecedentes como a las principales características de los diferentes mecanismos de medición. Para tal propósito, y con la intención de contribuir a la caracterización de la población de la provincia de Buenos Aires, se presentan datos capaces de comparar la información nacional con la de la Provincia.Facultad de Humanidades y Ciencias de la Educació

Autoxidation Products of the Methanolic Extract of the Leaves of Combretum micranthum Exert Antiviral Activity against Tomato Brown Rugose Fruit Virus (ToBRFV)

open7noTomato brown rugose fruit virus (ToBRFV) is a new damaging plant virus of great interest from both an economical and research point of view. ToBRFV is transmitted by contact, remains infective for months, and to-date, no resistant cultivars have been developed. Due to the relevance of this virus, new effective, sustainable, and operator-safe antiviral agents are needed. Thus, 4- hydroxybenzoic acid was identified as the main product of the alkaline autoxidation at high temperature of the methanolic extract of the leaves of C. micranthum, known for antiviral activity. The autoxidized extract and 4-hydroxybenzoic acid were assayed in in vitro experiments, in combination with a mechanical inoculation test of tomato plants. Catechinic acid, a common product of rearrangement of catechins in hot alkaline solution, was also tested. Degradation of the viral particles, evidenced by the absence of detectable ToBRFV RNA and the loss of virus infectivity, as a possible consequence of disassembly of the virus coat protein (CP), were shown. Homology modeling was then applied to prepare the protein model of ToBRFV CP, and its structure was optimized. Molecular docking simulation showed the interactions of the two compounds, with the amino acid residues responsible for CP-CP interactions. Catechinic acid showed the best binding energy value in comparison with ribavirin, an anti-tobamovirus agent.openValeria Iobbi, Anna Paola Lanteri, Andrea Minuto, Valentina Santoro, Giuseppe Ferrea, Paola Fossa, Angela BisioIobbi, Valeria; Paola Lanteri, Anna; Minuto, Andrea; Santoro, Valentina; Ferrea, Giuseppe; Fossa, Paola; Bisio, Angel

La alfabetización digital ciudadana para el desarrollo de competencias en el contexto educativo cubano

The digital transformation in the socio-educational sector is necessary for teachers, students and families and from there they develop digital skills that allow them to use the educational services that are at their disposal that contribute to generating a digital culture that allows them to function in any environment, for example. what is necessary is citizen digital literacy that addresses the main technological, didactic and techno-pedagogical knowledge. The objective of the article is to propose actions for citizen digital literacy of teachers that allow contextualizing the new teaching-learning trends for the improvement of classroom, institutional or territorial processes, and thus, is reflected in the level of development of competencies. digital for the use of educational services that are at your disposal. For its development, theoretical methods were used such as: logical historical, synthetic analytical, systemic-structural and as empirical methods, interviews, surveys and observations of teachers who work in the General Directorate of Education in Havana were used. Actions that are divided into two stages were validated, the first of diagnosis and awareness, and a second stage of practical intervention. From a socio-educational perspective, it was necessary to incorporate elements that contextualize educational institutions as the closest place and from which literacy variants are projected to the community that contribute to the development of digital competencies of teachers, students and the community, which are directly reflected in the digital culture of individuals, all of which allows interaction with the different digital educational services.La transformación digital en el sector socioeducativo, resulta necesario para docentes, educandos y familia y de ahí desarrollen competencias digitales que les permitan utilizar los servicios educativos que están a su disposición que contribuyan a generar una cultura digital que les permitan desenvolverse en cualquier entorno, por lo que es necesario una alfabetización digital ciudadana que aborde los principales saberes tecnológicos, didácticos y tecnopedagógicas. El objetivo del artículo es proponer acciones para la alfabetización digital ciudadana de los docentes que permita contextualizar las nuevas tendencias de enseñanza-aprendizaje para la mejora de los procesos áulicos, institucionales o territoriales, y así, se refleje en el nivel de desarrollo de las competencias digitales para el uso de servicios educativos que estén a su disposición.  Para su desarrollo se utilizaron métodos teóricos tales como: histórico lógico, analítico sintético, sistémico-estructural y como métodos empíricos se utilizaron entrevista, la encuesta y observación a docentes que laboran en la Dirección General de Educación en La Habana. Se validaron acciones que se encuentran divididas en dos etapas, la primera de diagnóstico y sensibilización, y una segunda etapa de intervención práctica. Desde una mirada socioeducativa fue necesario incorporar elementos que contextualicen a las instituciones educativas como el lugar más cercano y desde el cual, se proyecten a la comunidad variantes de alfabetización que tributen al desarrollo de competencias digitales docentes, de los educandos y de la comunidad, las cuales se reflejen directamente en la cultura digital de los individuos, todo lo cual permita la interacción con los diferentes servicios educativos digitales

Cell adhesion molecule L1 contributes to neuronal excitability regulating the function of voltage-gated Na+ channels

L1 (also known as L1CAM) is a trans-membrane glycoprotein mediating neuron-neuron adhesion through homophilic and heterophilic interactions. Although experimental evidence has implicated L1 in axonal outgrowth, fasciculation and pathfinding, its contribution to voltage-gated Na+ channel function and membrane excitability has remained unknown. Here, we show that firing rate, single cell spiking frequency and Na+ current density are all reduced in hippocampal excitatory neurons from L1-deficient mice both in culture and in slices owing to an overall reduced membrane expression of Na+ channels. Remarkably, normal firing activity was restored when L1 was reintroduced into L1-deficient excitatory neurons, indicating that abnormal firing patterns are not related to developmental abnormalities, but are a direct consequence of L1 deletion. Moreover, L1 deficiency leads to impairment of action potential initiation, most likely due to the loss of the interaction of L1 with ankyrin G that produces the delocalization of Na+ channels at the axonal initial segment. We conclude that L1 contributes to functional expression and localization of Na+ channels to the neuronal plasma membrane, ensuring correct initiation of action potential and normal firing activity

Characterization of a mice model of human epilepsy with Multi-Electrode Arrays

We applied microelectrode array (MEA) recordings to study the generation and propagation of epileptform activity in various connected regions of cortico-hippocampal slices obtained from SynapsinI/II/III knockout (TKO) mice and the effects of the synaptic vesicle-targeted anti epileptic drug levetiracetam (LEV). Synapsins (SynI, SynII and SynIII) are synaptic vesicle phosphoproteins playing a role in synaptic transmission and plasticity. TKO mice display an epileptic phenotype and mutation of the SYN1 gene is associated with epilepsy in man. We found that both interictal (IIC) and ictal (IC) discharges induced by 4AP were more pronounced and widespread in TKO mice, revealing a state of hyperexcitability of TKO networks. To get insight into the frequencies characterizing the IC seizures, we analyzed the average IC power spectral density (PSD) in the 10-50 Hz range in different cortical regions. TKO slices exhibited an increase of power for frequencies above 20Hz with respect to Wild- Type (TWT). To determine whether the hyperexcitability of TKO slices is also reflected by an increased spread of IC discharges and taking advantage of the spatial resolution of the MEA device, we measured the percentage of electrodes recording IC discharges over the total number of cortical electrodes. The spread of excitation was significantly higher in TKO slices than in TWT ones and treatment with LEV decreased the spread of IC discharges in the entorhinal of TKO slices. In order to better characterize the propagation of the IIC events in the hippocampus, we recently coupled MEA recordings with optical imaging using voltage-sensitive dyes by exploiting the possibility of simultaneous recordings with a high spatial and temporal resolution to reveal more detailed patterns of propagation

Validation of a high-density microelectrode array for acute brain slice recordings

Microelectrode arrays (MEAs) are employed to study extracellular electrical activity in neuronal tissues. Nevertheless, commercially available MEAs provide a limited number of recording sites and do not allow a precise identification of the spatio-temporal characterization of the recorded signal. To overcome this limitation, high density MEAs (HDMEA), based on CMOS technology, were recently developed and validated on dissociated preparations. The platform enables extracellular electrophysiological recordings from 4096 electrodes arranged in a squared area of 2.7 mm x 2.7 mm with inter-electrode distance of 21 μm at a sampling rate of 7.7 kHz/electrode. Here, we demonstrate the performances of this HDMEA platform for the acquisition of electrophysiological activity from acute brain slices. The unique recording performances and the large recording area of the chip permit the observation of fast propagating activities involving multiple areas. In our experimental paradigm, epileptic-like discharges were induced by treating hippocampal slices with 4-aminopyridine and/ or bicuculline. The HDMEA allowed us to clearly identify epileptic foci and to describe the involvement of cortical and hippocampal circuitries in the generation of the epileptiform activity. Furthermore, the HDMEA can be coupled with conventional extracellular electrodes for both stimulation and recording, giving the opportunity to perform standard short- and long-term plasticity protocols. We also show that HDMEA can be used in combination with fluorescence live imaging techniques such as Voltage Sensitive Dye recordings. The combination of complementary methodologies supports the HDMEA platform validation and paves the way to detailed electrophysiological studies

Large language models can support generation of standardized discharge summaries - A retrospective study utilizing ChatGPT-4 and electronic health records

OBJECTIVE: To evaluate whether psychiatric discharge summaries (DS) generated with ChatGPT-4 from electronic health records (EHR) can match the quality of DS written by psychiatric residents. METHODS: At a psychiatric primary care hospital, we compared 20 inpatient DS, written by residents, to those written with ChatGPT-4 from pseudonymized residents' notes of the patients' EHRs and a standardized prompt. 8 blinded psychiatry specialists rated both versions on a custom Likert scale from 1 to 5 across 15 quality subcategories. The primary outcome was the overall rating difference between the two groups. The secondary outcomes were the rating differences at the level of individual question, case, and rater. RESULTS: Human-written DS were rated significantly higher than AI (mean ratings: human 3.78, AI 3.12, p < 0.05). They surpassed AI significantly in 12/15 questions and 16/20 cases and were favored significantly by 7/8 raters. For "low expected correction effort", human DS were rated as 67 % favorable, 19 % neutral, and 14 % unfavorable, whereas AI-DS were rated as 22 % favorable, 33 % neutral, and 45 % unfavorable. Hallucinations were present in 40 % of AI-DS, with 37.5 % deemed highly clinically relevant. Minor content mistakes were found in 30 % of AI and 10 % of human DS. Raters correctly identified AI-DS with 81 % sensitivity and 75 % specificity. DISCUSSION: Overall, AI-DS did not match the quality of resident-written DS but performed similarly in 20% of cases and were rated as favorable for "low expected correction effort" in 22% of cases. AI-DS lacked most in content specificity, ability to distill key case information, and coherence but performed adequately in conciseness, adherence to formalities, relevance of included content, and form. CONCLUSION: LLM-written DS show potential as templates for physicians to finalize, potentially saving time in the future

Long-term decoding of movement force and direction with a wireless myoelectric implant

Objective. The ease of use and number of degrees of freedom of current myoelectric hand prostheses is limited by the information content and reliability of the surface electromyography (sEMG) signals used to control them. For example, cross-talk limits the capacity to pick up signals from small or deep muscles, such as the forearm muscles for distal arm amputations, or sites of targeted muscle reinnervation (TMR) for proximal amputations. Here we test if signals recorded from the fully implanted, induction-powered wireless Myoplant system allow long-term decoding of continuous as well as discrete movement parameters with better reliability than equivalent sEMG recordings. The Myoplant system uses a centralized implant to transmit broadband EMG activity from four distributed bipolar epimysial electrodes. Approach. Two Rhesus macaques received implants in their backs, while electrodes were placed in their upper arm. One of the monkeys was trained to do a cursor task via a haptic robot, allowing us to control the forces exerted by the animal during arm movements. The second animal was trained to perform a center-out reaching task on a touchscreen. We compared the implanted system with concurrent sEMG recordings by evaluating our ability to decode time-varying force in one animal and discrete reach directions in the other from multiple features extracted from the raw EMG signals. Main results. In both cases, data from the implant allowed a decoder trained with data from a single day to maintain an accurate decoding performance during the following months, which was not the case for concurrent surface EMG recordings conducted simultaneously over the same muscles. Significance. These results show that a fully implantable, centralized wireless EMG system is particularly suited for long-term stable decoding of dynamic movements in demanding applications such as advanced forelimb prosthetics in a wide range of configurations (distal amputations, TMR).German Federal Ministry for Education and Reseach (BMBF) grant No, 16SV3695, 16SV3699, 16SV3697 and 01GQ1005C, DFG Deutsche Forschungsgemeinschaft grant No. GA1475-C

Large-scale, high-resolution electrophysiological imaging of field potentials in brain slices with microelectronic multielectrode arrays

Multielectrode arrays (MEAs) are extensively used for electrophysiological studies on brain slices, but the spatial resolution and field of recording of conventional arrays are limited by the low number of electrodes available. Here, we present a large-scale array recording simultaneously from 4096 electrodes used to study propagating spontaneous and evoked network activity in acute murine cortico-hippocampal brain slices at unprecedented spatial and temporal resolution. We demonstrate that multiple chemically induced epileptiform episodes in the mouse cortex and hippocampus can be classified according to their spatio-temporal dynamics. Additionally, the large-scale and high-density features of our recording system enable the topological localization and quantification of the effects of antiepileptic drugs in local neuronal microcircuits, based on the distinct field potential propagation patterns. This novel high-resolution approach paves the way to detailed electrophysiological studies in brain circuits spanning spatial scales from single neurons up to the entire slice network