The future of direct cardiac reprogramming: any GMT cocktail variety?

Direct cardiac reprogramming has emerged as a novel therapeutic approach to treat and regenerate injured hearts through the direct conversion of fibroblasts into cardiac cells. Most studies have focused on the reprogramming of fibroblasts into induced cardiomyocytes (iCMs). The first study in which this technology was described, showed that at least a combination of three transcription factors, GATA4, MEF2C and TBX5 (GMT cocktail), was required for the reprogramming into iCMs in vitro using mouse cells. However, this was later demonstrated to be insufficient for the reprogramming of human cells and additional factors were required. Thereafter, most studies have focused on implementing reprogramming efficiency and obtaining fully reprogrammed and functional iCMs, by the incorporation of other transcription factors, microRNAs or small molecules to the original GMT cocktail. In this respect, great advances have been made in recent years. However, there is still no consensus on which of these GMT-based varieties is best, and robust and highly reproducible protocols are still urgently required, especially in the case of human cells. On the other hand, apart from CMs, other cells such as endothelial and smooth muscle cells to form new blood vessels will be fundamental for the correct reconstruction of damaged cardiac tissue. With this aim, several studies have centered on the direct reprogramming of fibroblasts into induced cardiac progenitor cells (iCPCs) able to give rise to all myocardial cell lineages. Especially interesting are reports in which multipotent and highly expandable mouse iCPCs have been obtained, suggesting that clinically relevant amounts of these cells could be created. However, as of yet, this has not been achieved with human iCPCs, and exactly what stage of maturity is appropriate for a cell therapy product remains an open question. Nonetheless, the major concern in regenerative medicine is the poor retention, survival, and engraftment of transplanted cells in the cardiac tissue. To circumvent this issue, several cell pre-conditioning approaches are currently being explored. As an alternative to cell injection, in vivo reprogramming may face fewer barriers for its translation to the clinic. This approach has achieved better results in terms of efficiency and iCMs maturity in mouse models, indicating that the heart environment can favor this process. In this context, in recent years some studies have focused on the development of safer delivery systems such as Sendai virus, Adenovirus, chemical cocktails or nanoparticles. This article provides an in-depth review of the in vitro and in vivo cardiac reprograming technology used in mouse and human cells to obtain iCMs and iCPCs, and discusses what challenges still lie ahead and what hurdles are to be overcome before results from this field can be transferred to the clinical settings

Educación rural y dispositivo evaluación en tiempos de ‘COVID-19’: voces de profesores de Matemática

Este artículo presenta algunos avances de una investigación de maestría que se titula “Dispositivo evaluación en contextos rurales: cartografiando experiencias al interior del aula de Matemática”, la cual inicio el camino investigativo basándose en los estudios desarrollados por Michel Foucault, buscando elaborar un trazado cartográfico en la perspectiva de Guilles Deleuze, Félix Guattari y Suely Rolnik. Esta investigación nos ha permitido dar muestra de cómo la evaluación presente en el currículo escolar de Matemática, opera como un dispositivo bajo algunas técnicas en los procesos escolares, inclusive en los tiempos de la pandemia provocada por el COVID-19. Con este artículo queremos mostrar las voces de algunos profesores que orientan el área de Matemática en tres Instituciones Educativas Rurales del Suroeste Antioqueño Colombiano, donde se dejan ver algunas (re)existencias de los procesos evaluativos desarrollados con los estudiantes, en este tiempo donde se enseña desde la distancia

Adherencia de las esporas de Beauveria bassiana formuladas en polvo y líquido sobre la broca del café

Traps with alcohol, as attractant, used to capture coffee berry borer adults (Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae) give the opportunity to deposit spores of Beauveria bassiana (Bals.) Vuill. (Ascomycota: Hypocreales) to auto-inoculate the adult attracted and to get the spores disseminated into the coffee field. Therefore, the aim of this study was to evaluate the capability of the coffee berry borer adult to pick up spores, in the form of powder, from a treated surface, suspension in oil [Kerosene, Carrier® and Kerosene+Carrier® (60:40)] and in sugar dilution at 5 and 10%. Three ways of adult exposition to the treated surfaces were evaluated. Adults walking on a surface treated with power allowed the beetles to pick up the highest number of spores. Second best expostition method was obtained when adults landed with open wings and the least efficient way of picking up spores was when they landed with closed wings. The most efficient formulation was spores applied as powder, followed by Carrier®, Kerosene+Carrier®, sugar in 5 and 10%. The lowest performance was obtained when the spores were applied using Kerosene alone.El uso de trampas con alcohol, como atrayente para la captura de losadultosde la broca del café (Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae), ofrece la oportunidad de colocar depósitos de esporas del hongo Beauveria bassiana (Bals.) Vuill. (Ascomycota: Hypocreales) para la auto-inoculación y la posterior diseminación del hongo en el campo. En este estudio, se tuvo por objetivo determinar la capacidad de los adultos de la broca para recoger esporas de superficies tratadas, con cuatro métodos de aplicación y tres métodos de exposición. Las esporas, se aplicaron en polvo, suspensión en aceite [Kerosene, Carrier® y Kerosene+Carrier® (60:40)] y en diluciones de azúcar al 5 y 10%. El mayor número de esporas recogidas, se obtuvo cuando las brocas caminaron sobre la superficie tratada con esporas en polvo. El segundo mejor método de exposición, se consiguió cuando las brocas aterrizaron sobre la superficie con las alas abiertas y el de menor adherencia, se encontró cuando las brocas aterrizaron con las alas cerradas. El tratamiento de aplicación que presentó mayor adherencia de las esporas, se obtuvo con las esporas en polvo, seguido por las formuladas en Carrier®, Kerosene, Carrier®, azúcar al 5 y al 10%. La menor adherencia se manifestó con las esporas formuladas en Kerosen

The volume of ERCP per endoscopist is associated with a higher technical success and a lower post-ERCP pancreatitis rate. A prospective analysis

Introduction: conflicting results have been reported regarding the influence of the annual volume of endoscopic retrograde cholangiopancreatography (ERCP) on outcome. Objective: to evaluate the influence of case volume on ERCP outcomes. Patients and methods: an analysis of a prospective database was performed, comparing the outcomes of ERCP in three consecutive periods defined by the number of endoscopists performing ERCP: five endoscopists in period I (P1), four in period II (P2) and three in period III (P3). Only patients with biliary ERCP in accessible and naïve papilla were included. Primary variables were cannulation rates and adverse effects (AE). The American Society of Gastrointestinal Endoscopy (ASGE) complexity grades III and IV were considered as highly complex procedures. Results: a total of 2,561 patients were included: 727 (P1), 972 (P2) and 862 (P3). There were no differences in age and sex between groups (p > 0.05). The cannulation rate was significantly higher in P2 and P3: 92.4 % vs 93.3 % vs 93 % (p = 0.037). The AE rate was 13.8 %, 12.6 % and 10.3 % (p > 0.05), respectively. The rate of post-ERCP pancreatitis was significantly lower in P3: 8.5 %, 7.3 % and 5 % (p = 0.01). The rate of complex procedures was 12 %, 14.8 % and 27 % (p < 0.0001), respectively. Two endoscopists participated in all periods and only one had significantly improved outcomes. Cannulation and post-ERCP pancreatitis rates remained significantly better in P3 after adjusting for sex, complexity and endoscopist. Conclusion: a higher annual volume of ERCP per endoscopist was associated with a higher rate of cannulation and a lower rate of post-ERCP pancreatitis, despite the greater complexity of the procedures. These beneficial effects seem to differ between endoscopists

GABA Concentration in Posterior Cingulate Cortex Predicts Putamen Response during Resting State fMRI

The role of neurotransmitters in the activity of resting state networks has been gaining attention and has become a field of research with magnetic resonance spectroscopy (MRS) being one of the key techniques. MRS permits the measurement of γ-aminobutyric acid (GABA) and glutamate levels, the central biochemical constituents of the excitation-inhibition balance in vivo. The inhibitory effects of GABA in the brain have been largely investigated in relation to the activity of resting state networks in functional magnetic resonance imaging (fMRI). In this study GABA concentration in the posterior cingulate cortex (PCC) was measured using single voxel spectra acquired with standard point resolved spectroscopy (PRESS) from 20 healthy male volunteers at 3 T. Resting state fMRI was consecutively measured and the values of GABA/Creatine+Phosphocreatine ratio (GABA ratio) were included in a general linear model matrix as a step of dual regression analysis in order to identify voxels whose neuroimaging metrics during rest were related to individual levels of the GABA ratio. Our data show that the connection strength of putamen to the default-mode network during resting state has a negative linear relationship with the GABA ratio measured in the PCC. These findings highlight the role of PCC and GABA in segregation of the motor input, which is an inherent condition that characterises resting stat

Cortical Response Variation with Different Sound Pressure Levels: A Combined Event-Related Potentials and fMRI Study

Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) provides high spatial and temporal resolution. In this study we combined EEG and fMRI to investigate the structures involved in the processing of different sound pressure levels (SPLs)

Imaging the where and when of tic generation and resting state networks in adult Tourette patients

Introduction: Tourette syndrome (TS) is a neuropsychiatric disorder with the core phenomenon of tics, whose origin and temporal pattern are unclear. We investigated the When and Where of tic generation and resting state networks (RSNs) via functional magnetic resonance imaging (fMRI).Methods: Tic-related activity and the underlying RSNs in adult TS were studied within one fMRI session. Participants were instructed to lie in the scanner and to let tics occur freely. Tic onset times, as determined by video-observance were used as regressors and added to preceding time-bins of 1 s duration each to detect prior activation. RSN were identified by independent component analysis (ICA) and correlated to disease severity by the means of dual regression.Results: Two seconds before a tic, the supplementary motor area (SMA), ventral primary motor cortex, primary sensorimotor cortex and parietal operculum exhibited activation; 1 s before a tic, the anterior cingulate, putamen, insula, amygdala, cerebellum and the extrastriatal-visual cortex exhibited activation; with tic-onset, the thalamus, central operculum, primary motor and somatosensory cortices exhibited activation. Analysis of resting state data resulted in 21 components including the so-called default-mode network. Network strength in those regions in SMA of two premotor ICA maps that were also active prior to tic occurrence, correlated significantly with disease severity according to the Yale Global Tic Severity Scale (YGTTS) scores.Discussion: We demonstrate that the temporal pattern of tic generation follows the cortico-striato-thalamo-cortical circuit, and that cortical structures precede subcortical activation. The analysis of spontaneous fluctuations highlights the role of cortical premotor structures. Our study corroborates the notion of TS as a network disorder in which abnormal RSN activity might contribute to the generation of tics in SMA

Removal of Pulse Artefact from EEG Data Recorded in MR Environment at 3T. Setting of ICA Parameters for Marking Artefactual Components: Application to Resting-State Data

Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) allow for a non-invasive investigation of cerebral functions with high temporal and spatial resolution. The main challenge of such integration is the removal of the pulse artefact (PA) that affects EEG signals recorded in the magnetic resonance (MR) scanner. Often applied techniques for this purpose are Optimal Basis Set (OBS) and Independent Component Analysis (ICA). The combination of OBS and ICA is increasingly used, since it can potentially improve the correction performed by each technique separately. The present study is focused on the OBS-ICA combination and is aimed at providing the optimal ICA parameters for PA correction in resting-state EEG data, where the information of interest is not specified in latency and amplitude as in, for example, evoked potential. A comparison between two intervals for ICA calculation and four methods for marking artefactual components was performed. The performance of the methods was discussed in terms of their capability to 1) remove the artefact and 2) preserve the information of interest. The analysis included 12 subjects and two resting-state datasets for each of them. The results showed that none of the signal lengths for the ICA calculation was highly preferable to the other. Among the methods for the identification of PA-related components, the one based on the wavelets transform of each component emerged as the best compromise between the effectiveness in removing PA and the conservation of the physiological neuronal content