The initial ingrowth of corticothalamic and thalamocortical projections was examined in mice at embryonic and perinatal stages. Fibers, in fixed brains, were labeled with the carbocyanine dye 1, 1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocianine perchlorate (DiI). By E13, the corticofugal fibers had entered the lowest intermediate zone through which they ran, turned over the corpus striatum, and left the cortex. The fibers were arranged in scattered bundles throughout the corpus striatum. At E14 corticofugal axons reached the internal capsule and at E14.5-E15 they established contact within the thalamus. Meanwhile, the thalamocortical afferents reached the neocortex at E13. At this time fibers ran tangentially within the intermediate zone, immediately underneath the cortical plate. By E14, the fibers had started to invade the subplate and, by E15, thalamocortical fibers had begun their radial growth into the cortex. Such radial growth proceeded steadily, invading each cortical layer as it differentiated cytoarchitectonically from the dense cortical plate. The first retrogradely labeled cells were detected at the cortical plate at E15. By the day of birth (E20), thalamocortical fibers had formed a dense branching system within layers VI and V. Our observations indicate that, in mice, the thalamic axons reach the cortex before corticothalamic projections enter the thalamic nuclei. Moreover, the results suggest that the pathway followed by each fiber system is different. By DiI injections into the internal capsule we have also determined that subplate cells are the first to send axons to the thalamus.

Cortical neurons are generated within the proliferative layer and follow a strict 'inside-out' gradient of migration and positioning, which determines the characteristic layering and pattern of neural connections in the adult cerebral cortex. Thus, directional migration of postmitotic neuroblasts towards layer I and regulation of the radial glia phenotype subserving cortical migration are central issues in corticogenesis. Recent studies showing that the gene disrupted in the reeler mutation--reelin--is expressed in Cajal-Retzius cells have indicated a role for these pioneer neurons in cortical migration. We show here that ablation of Cajal-Retzius cells in layer I by local application of domoic acid in newborn mice arrests migration of the late-generated neurons, destined to cortical layers II-III, that have been labeled by 5-bromodeoxyuridine injections administered at E16. In addition, degeneration of Cajal-Retzius cells in newborn mice dramatically decreases the number of radial glial apical processes identified by nestin-immunostaining, but increases the number of maturing glial fibrillary acidic protein-positive astrocytes. These findings support an essential role for Cajal-Retzius cells in neuronal migration and corticogenesis, by regulating the identity and function of radial glia and the radial glia-to-astrocyte transformation.

Digital health technologies offer significant opportunities to reshape current health care systems. From the adoption of electronic medical records to mobile health apps and other disruptive technologies, digital health solutions have promised a better quality of care at a more sustainable cost. However, the widescale adoption of these solutions is lagging behind. The most adverse scenarios often provide an opportunity to develop and test the capacity of digital health technologies to increase the efficiency of health care systems. Catalonia (Northeast Spain) is one of the most advanced regions in terms of digital health adoption across Europe. The region has a long tradition of health information exchange in the public health care sector and is currently implementing an ambitious digital health strategy. In this viewpoint, we discuss the crucial role digital health solutions play during the coronavirus disease (COVID-19) pandemic to support public health policies. We also report on the strategies currently deployed at scale during the outbreak in Catalonia.

Background: Multimorbidity is highly relevant for both service commissioning and clinical decision-making. Optimization of variables assessing multimorbidity in order to enhance chronic care management is an unmet need. To this end, we have explored the contribution of multimorbidity to predict use of healthcare resources at community level by comparing the predictive power of four different multimorbidity measures. Methods: A population health study including all citizens ≥18 years (n = 6,102,595) living in Catalonia (ES) on 31 December 2014 was done using registry data. Primary care service utilization during 2015 was evaluated through four outcome variables: A) Frequent attendants, B) Home care users, C) Social worker users, and, D) Polypharmacy. Prediction of the four outcome variables (A to D) was carried out with and without multimorbidity assessment. We compared the contributions to model fitting of the following multimorbidity measures: i) Charlson index; ii) Number of chronic diseases; iii) Clinical Risk Groups (CRG); and iv) Adjusted Morbidity Groups (GMA). Results: The discrimination of the models (AUC) increased by including multimorbidity as covariate into the models, namely: A) Frequent attendants (0.771 vs 0.853), B) Home care users (0.862 vs 0.890), C) Social worker users (0.809 vs 0.872), and, D) Polypharmacy (0.835 vs 0.912). GMA showed the highest predictive power for all outcomes except for polypharmacy where it was slightly below than CRG. Conclusions: We confirmed that multimorbidity assessment enhanced prediction of use of healthcare resources at community level. The Catalan population-based risk assessment tool based on GMA presented the best combination of predictive power and applicability.

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