Gene regulatory landscape of cerebral cortex folding.

Folding of the cerebral cortex is a key aspect of mammalian brain development and evolution, and defects are linked to severe neurological disorders. Primary folding occurs in highly stereotyped patterns that are predefined in the cortical germinal zones by a transcriptomic protomap. The gene regulatory landscape governing the emergence of this folding protomap remains unknown. We characterized the spatiotemporal dynamics of gene expression and active epigenetic landscape (H3K27ac) across prospective folds and fissures in ferret. Our results show that the transcriptomic protomap begins to emerge at early embryonic stages, and it involves cell-fate signaling pathways. The H3K27ac landscape reveals developmental cell-fate restriction and engages known developmental regulators, including the transcription factor Cux2. Manipulating Cux2 expression in cortical progenitors changed their proliferation and the folding pattern in ferret, caused by selective transcriptional changes as revealed by single-cell RNA sequencing analyses. Our findings highlight the key relevance of epigenetic mechanisms in defining the patterns of cerebral cortex folding.

UCO Physical Rehabilitation: New Dataset and Study of Human Pose Estimation Methods on Physical Rehabilitation Exercises.

Physical rehabilitation plays a crucial role in restoring motor function following injuries or surgeries. However, the challenge of overcrowded waiting lists often hampers doctors' ability to monitor patients' recovery progress in person. Deep Learning methods offer a solution by enabling doctors to optimize their time with each patient and distinguish between those requiring specific attention and those making positive progress. Doctors use the flexion angle of limbs as a cue to assess a patient's mobility level during rehabilitation. From a Computer Vision perspective, this task can be framed as automatically estimating the pose of the target body limbs in an image. The objectives of this study can be summarized as follows: (i) evaluating and comparing multiple pose estimation methods; (ii) analyzing how the subject's position and camera viewpoint impact the estimation; and (iii) determining whether 3D estimation methods are necessary or if 2D estimation suffices for this purpose. To conduct this technical study, and due to the limited availability of public datasets related to physical rehabilitation exercises, we introduced a new dataset featuring 27 individuals performing eight diverse physical rehabilitation exercises focusing on various limbs and body positions. Each exercise was recorded using five RGB cameras capturing different viewpoints of the person. An infrared tracking system named OptiTrack was utilized to establish the ground truth positions of the joints in the limbs under study. The results, supported by statistical tests, show that not all state-of-the-art pose estimators perform equally in the presented situations (e.g., patient lying on the stretcher vs. standing). Statistical differences exist between camera viewpoints, with the frontal view being the most convenient. Additionally, the study concludes that 2D pose estimators are adequate for estimating joint angles given the selected camera viewpoints.

Guía de Práctica Clínica en atresia esofágica / Clinical practice guide on esophageal atresia

La atresia esofágica es una de las anomalías congénitas más frecuentes en la práctica quirúrgica neonatal. Se estima que tiene una incidencia de 1 por cada 3500 recién nacidos vivos a nivel mundial. La preparación de guías de actuación y protocolos asistenciales es tendencia en la práctica médica actual. Esta Guía de Práctica Clínica se elaboró respondiendo a la necesidad de protocolizar la atención médico-quirúrgica de la atresia esofágica. En el Centro Territorial de Cirugía Neonatal de Holguín, donde se regionaliza la atención a neonatos de las cinco provincias orientales del país con afecciones congénitas y quirúrgicas de alta complejidad, la atresia esofágica fue la afección quirúrgica más frecuente en los últimos diez años, con una supervivencia ascendente que alcanzó 94,4 por ciento en 2019. La guía que se presenta se aprobó en el Primer Consenso Nacional de Guías de Prácticas Clínicas en Cirugía Pediátrica, en Varadero, Matanzas en 2019. Incluye las principales pautas para el diagnóstico, tratamiento y seguimiento de los pacientes afectados y se considera una herramienta eficiente para mejorar los resultados en la asistencia médica y quirúrgica neonatal(AU)

Esophageal atresia is one of the most common congenital anomalies in neonatal surgical practice. It is estimated to have an incidence of 1 per 3500 live newborns globally. The preparation of action guides and care protocols is a trend in current medical practice. This Clinical Practice Guide was prepared in response to the need to protocolize the medical-surgical care of esophageal atresia. In the Territorial Center for Neonatal Surgery of Holguín, where the care of neonates from the five eastern provinces of the country with congenital and surgical conditions of high complexity is regionalized, esophageal atresia was the most frequent surgical condition in the last ten years, with an ascending survival that reached 94.4 percent in 2019. The guideline presented was approved in the First National Consensus of Clinical Practice Guidelines in Pediatric Surgery, in Varadero, Matanzas in 2019. It includes the main guidelines for the diagnosis, treatment and follow-up of affected patients and is considered an efficient tool to improve outcomes in neonatal medical and surgical care(AU)

Secondary loss of miR-3607 reduced cortical progenitor amplification during rodent evolution.

The evolutionary expansion and folding of the mammalian cerebral cortex resulted from amplification of progenitor cells during embryonic development. This process was reversed in the rodent lineage after splitting from primates, leading to smaller and smooth brains. Genetic mechanisms underlying this secondary loss in rodent evolution remain unknown. We show that microRNA miR-3607 is expressed embryonically in the large cortex of primates and ferret, distant from the primate-rodent lineage, but not in mouse. Experimental expression of miR-3607 in embryonic mouse cortex led to increased Wnt/ß-catenin signaling, amplification of radial glia cells (RGCs), and expansion of the ventricular zone (VZ), via blocking the ß-catenin inhibitor APC (adenomatous polyposis coli). Accordingly, loss of endogenous miR-3607 in ferret reduced RGC proliferation, while overexpression in human cerebral organoids promoted VZ expansion. Our results identify a gene selected for secondary loss during mammalian evolution to limit RGC amplification and, potentially, cortex size in rodents.

Predictors of perfusion computed tomography alterations in stroke mimics attended as stroke code.

BACKGROUND AND PURPOSE: Stroke mimics (SMs) account for a significant number of patients attended as stroke code (SC) with an increasing number over the years. Recent studies show perfusion computed tomography (PCT) alterations in some SMs, especially in seizures. The objective of our study was to evaluate the clinical characteristics and PCT alterations in SMs attended as SC in order to identify potential predictors of PCT alterations in SMs. METHODS: A retrospective study was performed including all SC activations undergoing a multimodal CT study including non-enhanced computed tomography (CT), CT angiography and PCT, as part of our SC protocol, over 39 months. Patients with a final diagnosis of SM after complete diagnosis work-up were therefore selected. Clinical variables, diagnosis, PCT alteration patterns and type of map affected (Tmax or time to peak, cerebral blood flow and cerebral blood volume) were registered. RESULTS: Stroke mimics represent up to 16% (284/1761) of SCs with a complete multimodal study according to our series. Amongst SMs, 26% (74/284) showed PCT alterations. PCT abnormalities are more prevalent in seizures and status epilepticus and the main pattern is alteration of the time to peak map, of unilateral hemispheric distribution or of non-vascular territory. In our series, the independent predictors of alteration in PCT in SMs are aphasia, female sex and older age. CONCLUSIONS: Perfusion computed tomography alterations can be found amongst almost a third of SMs attended as SC, especially older women presenting with aphasia with a final diagnosis of epileptic seizures and status epilepticus.

Repression of Irs2 by let-7 miRNAs is essential for homeostasis of the telencephalic neuroepithelium.

Structural integrity and cellular homeostasis of the embryonic stem cell niche are critical for normal tissue development. In the telencephalic neuroepithelium, this is controlled in part by cell adhesion molecules and regulators of progenitor cell lineage, but the specific orchestration of these processes remains unknown. Here, we studied the role of microRNAs in the embryonic telencephalon as key regulators of gene expression. By using the early recombiner Rx-Cre mouse, we identify novel and critical roles of miRNAs in early brain development, demonstrating they are essential to preserve the cellular homeostasis and structural integrity of the telencephalic neuroepithelium. We show that Rx-Cre;DicerF/F mouse embryos have a severe disruption of the telencephalic apical junction belt, followed by invagination of the ventricular surface and formation of hyperproliferative rosettes. Transcriptome analyses and functional experiments in vivo show that these defects result from upregulation of Irs2 upon loss of let-7 miRNAs in an apoptosis-independent manner. Our results reveal an unprecedented relevance of miRNAs in early forebrain development, with potential mechanistic implications in pediatric brain cancer.

Language hemispheric dominance analyzed with magnetic resonance DTI: correlation with the Wada test.

OBJECTIVE: Language lateralization is a major concern in some patients with pharmacoresistant epilepsy who will face surgery; in these patients, hemispheric dominance testing is essential to avoid further complications. The Wada test is considered the gold standard examination for language localization, but is invasive and requires many human and material resources. Functional MRI and tractography with diffusion tensor imaging (DTI) have demonstrated that they could be useful for locating language in epilepsy surgery, but there is no evidence of the correlation between the Wada test and DTI MRI in language dominance. METHODS: The authors performed a retrospective review of patients who underwent a Wada test before epilepsy surgery at their institution from 2012 to 2017. The authors retrospectively analyzed fractional anisotropy (FA), number and length of fibers, and volume of the arcuate fasciculus and uncinate fasciculus, comparing dominant and nondominant hemispheres. RESULTS: Ten patients with temporal lobe epilepsy were reviewed. Statistical analysis showed that the mean FA of the arcuate fasciculus in the dominant hemisphere was higher than in the nondominant hemisphere (0.369 vs 0.329, p = 0.049). Also, the number of fibers in the arcuate fasciculus was greater in the dominant hemisphere (881.5 vs 305.4, p = 0.003). However, no differences were found in the FA of the uncinate fasciculus or number of fibers between hemispheres. The length of fibers of the uncinate fasciculus was longer in the dominant side (74.4 vs 50.1 mm, p = 0.05). Volume in both bundles was more prominent in the dominant hemisphere (12.12 vs 6.48 cm3, p = 0.004, in the arcuate fasciculus, and 8.41 vs 4.16 cm3, p = 0.018, in the uncinate fasciculus). Finally, these parameters were compared in patients in whom the seizure focus was situated in the dominant hemisphere: FA (0.37 vs 0.30, p = 0.05), number of fibers (114.4 vs 315.6, p = 0.014), and volume (12.58 vs 5.88 cm3, p = 0.035) in the arcuate fasciculus were found to be statistically significantly higher in the dominant hemispheres. Linear discriminant analysis of FA, number of fibers, and volume of the arcuate fasciculus showed a correct discrimination in 80% of patients (p = 0.024). CONCLUSIONS: The analysis of the arcuate fasciculus and other tract bundles by DTI could be a useful tool for language location testing in the preoperative study of patients with refractory epilepsy.

Evolución histórica del proceso de atención al neonato quirúrgico en Cirugía Pediátrica / Historical evolution of the caring process to the surgical newborn in Pediatric Surgery

RESUMEN Introducción: la evolución histórica del proceso de atención al neonato quirúrgico en Cirugía Pediátrica se realizó teniendo como hito la creación de la Unidad de Cuidados Intensivos Neonatales por primera vez en Cuba, lo que significó un cambio en la calidad de la atención al recién nacido. Objetivo: determinar las características que definieron la evolución histórica del proceso de atención al neonato quirúrgico en Cirugía Pediátrica desde 1970 hasta la actualidad. Método: se utilizaron los métodos histórico lógico y enfoque sistémico para el estudio y la caracterización de las etapas del proceso de atención. Resultados: a partir de la década de 1970 se identificaron cuatro etapas del proceso de atención al neonato quirúrgico en Cuba: inicio (1970), fortalecimiento (1980), nuevas estrategias (1990), así como actualidad y proyecciones desde el año 2000, además se determinó el movimiento tendencial del mismo. Conclusiones: las etapas propuestas caracterizan el proceso de atención al neonato quirúrgico en Cirugía Pediátrica en Cuba y son: I Etapa: 1970 a 1979. Inicio de la atención médica al neonato quirúrgico, II Etapa: 1980 a 1989. Fortalecimiento de la atención médica al neonato quirúrgico. III Etapa: 1990 a 1999. Nuevas estrategias en la atención médica al neonato quirúrgico y IV Etapa: 2000 - 2018. Actualidad y proyecciones en la atención médica al neonato quirúrgico.

ABSTRACT Introduction: in Cuba, surgical newborn intensive care evolution has come up with the creation of Neonatal Intensive Care Unit. For the first time, newborns´ quality care has made a meaningful change in our health service quality. Objective: to figure out historical evolution characteristics of newborns´ surgical attention in Pediatric Surgery, since 1970 until nowadays. Method: we used the logical historical method, sistemic approach and stages of neonatal caring process. Results: in Cuba, since the 1970's four surgical newborn caring process stages were identified: beginning (1970), strenghening (1980), new strategics (1990). Since 2000, the updates and visualizations also determined this trend. Conclusions: previous stages define the surgical process newborns´ medical care inside Pediatric Surgery, in Cuba. We identified the following: Stage 1: 1970-1979 Beginning, stage 2: 1980-1989 Strenghening of medical attention to surgical newborn. Stage 3: 1990-1999 new medical attention strategics to the surgical newborn. Stage 4: 2000-2018 Current proyections of medical attention to the surgical newborn.

Prediction of Laterality in Temporal Lobe Epilepsy Using White Matter Diffusion Metrics.

BACKGROUND: Diagnostic methods of the epileptogenic area continue to be a challenge in epilepsy surgery research. We hypothesized that temporal lobe epilepsy (TLE) will result in white matter changes that can be detected using diffusion tensor imaging. Measurement of white matter diffusivity will therefore be useful for presurgical assessment. METHODS: Twelve patients with TLE who had undergone temporal lobectomy and amygdalohippocampectomy were included. In 6 patients, magnetic resonance imaging (MRI) showed evidence of mesial temporal sclerosis (m-TLE), whereas the 6 remaining MRI studies were informed without any abnormality (nl-TLE). All had excellent outcomes from surgery. Patients were compared with 12 age- and sex-matched controls. Five pairs of white matter fiber tracts were traced, and fiber tract fractional anisotropy and mean diffusivity were calculated. RESULTS: There were several alterations in diffusion parameters in white matter tracts, both ipsilateral and on the contralateral side, these alterations were more pronounced in the hemisphere ipsilateral to the epileptogenic focus. m-TLE patients had more alterations on ipsilateral side than nl-TLE patients, but similar alterations on contralateral side and bilateral fornix. The discriminant function analysis successfully lateralized all the patients with left TLE, 83.3% of the patients with right TLE, and all nl-TLE. CONCLUSIONS: Our results suggest that there are alterations in diffusion parameters in white matter tracts both in m-TLE and nl-TLE patients. Diffusion tensor imaging could be a useful presurgical tool to help establish the laterality of TLE, including patients with "normal" MRI. Further studies with a larger number of patients would be necessary to confirm these results.

La supervivencia en neonatos con afecciones complejas en Cirugía Pediátrica / Neonates' survival from complex conditions after Pediatric Surgery

RESUMEN Introducción: el análisis de supervivencia es uno de los métodos estadísticos más empleado en los estudios clínicos. Objetivo: determinar la influencia de factores de riesgo en la supervivencia de los neonatos con afecciones complejas en Cirugía Pediátrica. Método: en este trabajo se estudiaron los pacientes atendidos en el Centro Regional de Cirugía Neonatal de Holguín, desde el 1ro de enero de 1994 hasta el 31 de diciembre del 2015. El universo estuvo constituido por 382 niños y la muestra por 295, con un tiempo de seguimiento de hasta 28 días. Se analizaron las variables como: peso al nacer, edad gestacional y anomalías asociadas; según los factores de riesgo como: bajo peso al nacer, neonato pretérmino y anomalías asociadas; así como su influencia en la supervivencia. Con la ayuda del paquete estadístico SPSS versión 15 sobre Windows XP, se efectuó el análisis de las curvas de supervivencia por el método Kaplan-Meier, y los factores de riesgo por el método Log-Rank. Resultados: del total de la muestra (n=295), se obtienen 66 neonatos con nacimiento pretérmino (22,4%), 82 con bajo peso al nacer (27,8%) y 154 con anomalías asociadas (52,2%); siendo este el factor de riesgo predominante. En dichos pacientes, se aprecia un alto número de eventos con influencia en su supervivencia, durante el seguimiento del período neonatal. El evento final ocurrió en 61 neonatos (20,7%). La media en el tiempo de supervivencia de los neonatos con afecciones complejas en Cirugía Pediátrica fue de 23 días. Conclusiones: en la supervivencia de los pacientes influyeron los factores de riesgo estudiados. La sepsis severa fue la causa directa de muerte que predominó.

ABSTRACT Introduction: survival study is one of the most used statistical methods in the clinical field. Objective: to determine the influence of risk factors over neonates´ survival form complex conditions after Pediatric Surgery. Method: in this work we studied patients attended in the Regional Center of Neonatal Surgery of Holguín, from January 1st, 1994 to December 31st, 2015. Universe was 382 neonates and the sample was 295, monitored during 28 days. Analyzed variables were: birth weight, gestational age and associated anomalies; according to its risk factors like: low birth weight, preterm neonates and associated anomalies, as well as their influence on neonates 'survival. By the use of statistical package SPSS version 15 on Windows XP, survival curves were analyzed by the Kaplan-Meier method and the risk factors by Log-Rank. Results: of the total sample (n=295) 66 neonates were preterm births (22.4%); 82 low birth weight (27.8%) and 154 showed associated anomalies (52.2%) as the main risk factor. Patients studied showed high numbers of events and their influence on survival during neonatal period. The final event occurred to 61 neonates (20.7%). Conclusions: risk factors studied were influenced by patients´ survival and the direct cause of death was severe sepsis.

Papel de la imagen por tensor de difusión en el estudio prequirúrgico de la epilepsia del lóbulo temporal / The role of diffusion tensor imaging in the pre-surgical study of temporal lobe epilepsy

Introducción. La imagen por tensor de difusión (DTI) es una técnica no invasiva que puede ser utilizada para evaluar la integridad de la sustancia blanca cerebral. Objetivo. Investigar la utilidad de la DTI en pacientes con epilepsia del lóbulo temporal (ELT) y ver su relación con la lateralización del foco epileptógeno en estos pacientes. Pacientes y métodos. Se analizan 11 pacientes diagnosticados de ELT según el protocolo de evaluación prequirúrgica de nuestra unidad de epilepsia, y libres de crisis a los dos años de la realización de una lobectomía temporal más amigdalohipocampectomía (técnica de Spencer). Como parte de su estudio preoperatorio, se realiza una resonancia magnética cerebral de 1,5 T con secuencia de tensor de difusión y se estudian, mediante un análisis basado en vóxel, las diferencias en la conectividad entre el hemisferio intervenido y el contralateral. Resultados. Comparado con el hemisferio contralateral, se observó una reducción de la anisotropía fraccional estadísticamente significativa (p < 0,05) en el cuerpo calloso, el cíngulo, el fascículo longitudinal superior, las radiaciones talámicas anteriores, la cápsula interna, los núcleos ventral lateral y pulvinar del tálamo, el fascículo frontooccipital inferior, el fascículo uncinado, el fascículo longitudinal inferior y el giro parahipocampal ipsilaterales al foco epileptógeno. Conclusiones. La caracterización de las anormalidades en la conectividad de la sustancia blanca cerebral, a través de la DTI en pacientes con ELT, puede tener un valor importante para la lateralización del foco epileptógeno en la evaluación prequirúrgica. Serían necesarios estudios con un número más elevado de pacientes para confirmar estos resultados (AU)

Introduction. Diffusion tensor imaging (DTI) is a non-invasive technique that can be used to assess the integrity of the white matter in the brain. Aims. To investigate the usefulness of DTI in patients with temporal lobe epilepsy (TLE) and to observe its relationship with lateralisation of the epileptogenic focus in these patients. Patients and methods. We analysed 11 patients diagnosed with TLE in accordance with the pre-surgical protocol of our epilepsy unit, and who were seizure-free two years after performing a temporal lobectomy plus amygdalohippocampectomy (Spencer technique). As part of their pre-operative study, a 1.5 T magnetic resonance brain scan with diffusion tensor imaging was performed. A voxel-based analysis was then employed to study the differences in connectivity between the hemisphere that underwent surgery and the contralateral hemisphere. Results. Compared with the contralateral hemisphere, a statistically significant reduction in fractional anisotropy (p < 0.05) was observed in the corpus callosum, the cingulate, the superior longitudinal fasciculus, the anterior thalamic radiations, the internal capsule, the ventral lateral and pulvinar nuclei of the thalamus, the inferior frontooccipital fasciculus, the uncinate fasciculus, the inferior longitudinal fasciculus and the parahippocampal gyrus, all ipsilateral to the epileptogenic focus. Conclusions. The characterisation of the abnormalities in the connectivity of the cerebral white matter, by means of DTI in patients with TLE, can be a valuable aid for the lateralisation of the epileptogenic focus in the pre-surgical evaluation of these patients. Further studies with a higher number of patients would be needed to confirm these results (AU)