Resting state networks in patients with acute disorders of consciousness after severe traumatic brain injury.

OBJECTIVES: This study aims to describe resting state networks (RSN) in patients with disorders of consciousness (DOC)s after acute severe traumatic brain injury (TBI). METHODS: Adult patients with TBI with a GCS score <8 who remained in a coma, minimally conscious state (MCS), or unresponsive wakefulness syndrome (UWS), between 2017 and 2020 were included. Blood-oxygen-level dependent imaging was performed to compare their RSN with 10 healthy volunteers. RESULTS: Of a total of 293 patients evaluated, only 13 patients were included according to inclusion criteria: 7 in coma (54%), 2 in MCS (15%), and 4 (31%) had an UWS. RSN analysis showed that the default mode network (DMN) was present and symmetric in 6 patients (46%), absent in 1 (8%), and asymmetric in 6 (46%). The executive control network (ECN) was present in all patients but was asymmetric in 3 (23%). The right ECN was absent in 2 patients (15%) and the left ECN in 1 (7%). The medial visual network was present in 11 (85%) patients. Finally, the cerebellar network was symmetric in 8 patients (62%), asymmetric in 1 (8%), and absent in 4 (30%). CONCLUSIONS: A substantial impairment in activation of RSN is demonstrated in patients with DOC after severe TBI in comparison with healthy subjects. Three patterns of activation were found: normal/complete activation, 2) asymmetric activation or partially absent, and 3) absent activation.

Slits affect the timely migration of neural crest cells via Robo receptor.

BACKGROUND: Neural crest cells emerge by delamination from the dorsal neural tube and give rise to various components of the peripheral nervous system in vertebrate embryos. These cells change from non-motile into highly motile cells migrating to distant areas before further differentiation. Mechanisms controlling delamination and subsequent migration of neural crest cells are not fully understood. Slit2, a chemorepellant for axonal guidance that repels and stimulates motility of trunk neural crest cells away from the gut has recently been suggested to be a tumor suppressor molecule. The goal of this study was to further investigate the role of Slit2 in trunk neural crest cell migration by constitutive expression in neural crest cells. RESULTS: We found that Slit gain-of-function significantly impaired neural crest cell migration while Slit loss-of-function favored migration. In addition, we observed that the distribution of key cytoskeletal markers was disrupted in both gain and loss of function instances. CONCLUSIONS: These findings suggest that Slit molecules might be involved in the processes that allow neural crest cells to begin migrating and transitioning to a mesenchymal type.

Revising the diversity within the Dwarf Dog-faced Bat, Molossopstemminckii (Chiroptera, Molossidae), with the revalidation of the endangered Molossopsgriseiventer.

The genus Molossops includes two monotypic species of insectivore bats distributed in South America: Molossopsneglectus and Molossopstemminckii. Both can be differentiated, based on sizes, M.temminckii being smaller (forearm less than 33 mm). Despite being monotypic, at least two additional subspecies have been described for M.temminckii, of which M.temminckiigriseiventer from the inter-Andean Valley of the Magdalena River in Colombia might represent a valid taxon. To test the taxonomic status of M.t.griseiventer, we reviewed specimens of M.temminckii from cis- and trans-Andean localities in Colombia. We used Cytochrome-b and Cytochrome Oxidase I comparisons to test the phylogenetic position of cis- and trans-Andean samples and compared qualitative morphology, morphometric and bioacoustics. Our results show that M.t.griseiventer is differentiated from cis-Andean specimens, providing further evidence of its validity at the species level. Furthermore, M.temminckii (sensu stricto) is also distributed in Colombia, but both M.griseiventer and M.temminckii are allopatric, with the Andes acting as a barrier. The specific identity of the specimens from the Caribbean Region of Colombia needs a new evaluation, but our results clearly show that the diversity of Molossops is underestimated.

Confirming the presence of Lasiurusfrantzii (Peters, 1870) (Chiroptera, Vespertilionidae) in South America: more questions than answers.

The western or desert red bat, Lasiurusfrantzii, is a cryptic insectivore species distributed in the Neotropics from Mexico south through Central America to Panama. L.frantzii was long considered a subspecies of the red bat, Lasiurusblossevillii, but recently it was elevated to full-species status based on genetic information. Here we present evidence of the presence of L.frantzii in the Andean Region of Colombia, confirming the species' presence in South America; the new record, from 3836 m a.s.l., is also the highest elevation known for the species. We suggest that L.frantzii might be widely distributed in trans-Andean areas of Colombia, Ecuador, Venezuela, and perhaps Peru and Bolivia. However, a review and exploration of additional morphological traits to identify the species are necessary because of the uncertainty of the distribution of L.frantzii.

Consensus Statement: Importance of Timely Access to Multiple Myeloma Diagnosis and Treatment in Central America and the Caribbean.

Background: In Central America and the Caribbean, multiple myeloma (MM) patients face significant barriers to diagnosis and treatment. The aim of this study is to describe the current situation of MM in the region, discuss the current barriers to timely diagnosis and proper treatment, and develop consensus recommendations to address these issues. Methods: Nine experts from five countries took part in a virtual consensus meeting on MM in Central America and the Caribbean. During the meeting, experts analyzed the disease burden, the current conditions for disease management, and access to treatment in the region. The participants reached a consensus on the extent of the problem and the necessary measures. Results: Hard evidence on the incidence and prevalence of MM in the region is scarce, but the experts perceive an increase in MM cases. The lack of data on the direct and indirect costs at the local and regional levels obscures the impact of the disease and limits awareness among decision-makers. Most patients are diagnosed late and face long waiting times and geographical barriers to access treatment. Access to efficacious innovative therapies that increase survival time is limited due to access barriers within health systems. Conclusions: There was consensus on five recommendations: 1) to generate evidence; 2) to educate the public; 3) to increase timely diagnosis and facilitate access to treatment; 4) to promote interaction, collaboration, and participation among all sectors involved in the decision-making process; and 5) to guarantee timely access to new therapies.

Beginning the quest: phylogenetic hypothesis and identification of evolutionary lineages in bats of the genus Micronycteris (Chiroptera, Phyllostomidae).

Thirteen species of Neotropical bats of the genus Micronycteris are currently recognized and are allocated to four subgenera Leuconycteris, Micronycteris, Schizonycteris, and Xenonectes. Despite that, the presence of polyphyletic clades in molecular phylogenies suggests that its diversity is underestimated. Additionally, the incorrect identification of some genetic sequences, the incorrect assignation of available valid names, and restricted geographic sampling have biased the identification of independently evolutionary lineages within Micronycteris. In this study, several unknown genealogical lineages in the genus are identified and an updated phylogenetic hypothesis is proposed using mitochondrial and nuclear DNA fragments. The phylogenetic analyses congruently showed all individuals in four well-supported subgenera, but M. schmidtorum was revealed as the sister taxon of M. brosseti in the subgenus Leuconycteris. Twenty-seven different genealogical lineages were identified. These included eight confirmed species: M. brosseti, M. buriri, M. giovanniae, M. matses, M. schmidtorum, M. simmonsae, M. tresamici, and M. yatesi. Nineteen either allopatric or parapatric candidate species were also confirmed, two within the M. hirsuta complex, nine within the M. megalotis complex, seven within the M. minuta complex, and one corresponding to "M. sp.". These results revealed an extensive undescribed diversity within each subgenus of Micronycteris. Nevertheless, the evolutionary processes associated with the specific radiations are poorly understood. This is just the beginning of the assessment of the taxonomy and systematics of Micronycteris, which requires additional integrative taxonomical approaches for its advance.

Structural and functional connectivity of the ascending arousal network for prediction of outcome in patients with acute disorders of consciousness.

To determine the role of early acquisition of blood oxygen level-dependent (BOLD) signals and diffusion tensor imaging (DTI) for analysis of the connectivity of the ascending arousal network (AAN) in predicting neurological outcomes after acute traumatic brain injury (TBI), cardiopulmonary arrest (CPA), or stroke. A prospective analysis of 50 comatose patients was performed during their ICU stay. Image processing was conducted to assess structural and functional connectivity of the AAN. Outcomes were evaluated after 3 and 6 months. Nineteen patients (38%) had stroke, 18 (36%) CPA, and 13 (26%) TBI. Twenty-three patients were comatose (44%), 11 were in a minimally conscious state (20%), and 16 had unresponsive wakefulness syndrome (32%). Univariate analysis demonstrated that measurements of diffusivity, functional connectivity, and numbers of fibers in the gray matter, white matter, whole brain, midbrain reticular formation, and pontis oralis nucleus may serve as predictive biomarkers of outcome depending on the diagnosis. Multivariate analysis demonstrated a correlation of the predicted value and the real outcome for each separate diagnosis and for all the etiologies together. Findings suggest that the above imaging biomarkers may have a predictive role for the outcome of comatose patients after acute TBI, CPA, or stroke.

Time-Delay Latency of Resting-State Blood Oxygen Level-Dependent Signal Related to the Level of Consciousness in Patients with Severe Consciousness Impairment.

Recent evidence on resting-state functional magnetic resonance imaging (rs-fMRI) suggests that healthy human brains have a temporal organization represented in a widely complex time-delay structure. This structure seems to underlie brain communication flow, integration/propagation of brain activity, as well as information processing. Therefore, it is probably linked to the emergence of highly coordinated complex brain phenomena, such as consciousness. Nevertheless, possible changes in this structure during an altered state of consciousness remain poorly investigated. In this work, we hypothesized that due to a disruption in high-order functions and alterations of the brain communication flow, patients with disorders of consciousness (DOC) might exhibit changes in their time-delay structure of spontaneous brain activity. We explored this hypothesis by comparing the time-delay projections from fMRI resting-state data acquired in resting state from 48 patients with DOC and 27 healthy controls (HC) subjects. Results suggest that time-delay structure modifies for patients with DOC conditions when compared with HC. Specifically, the average value and the directionality of latency inside the midcingulate cortex (mCC) shift with the level of consciousness. In particular, positive values of latency inside the mCC relate to preserved states of consciousness, whereas negative values change proportionally with the level of consciousness in patients with DOC. These results suggest that the mCC may play a critical role as an integrator of brain activity in HC subjects, but this role vanishes in an altered state of consciousness.

Reconfiguration of large-scale functional connectivity in patients with disorders of consciousness.

INTRODUCTION: Functional connectivity alterations within individual resting state networks (RSNs) are linked to disorders of consciousness (DOC). If these alterations influence the interaction quality with other RNSs, then, brain alterations in patients with DOC would be characterized by connectivity changes in the large-scale model composed of RSNs. How are functional interactions between RSNs influenced by internal alterations of individual RSNs? Do the functional alterations induced by DOC change some key properties of the large-scale network, which have been suggested to be critical for the consciousness emergence? Here, we use network analysis to measure functional connectivity in patients with DOC and address these questions. We hypothesized that network properties provide descriptions of brain functional reconfiguration associated with consciousness alterations. METHODS: We apply nodal and global network measurements to study the reconfiguration linked with the disease severity. We study changes in integration, segregation, and centrality properties of the functional connectivity between the RSNs in subjects with different levels of consciousness. RESULTS: Our analysis indicates that nodal measurements are more sensitive to disease severity than global measurements, particularly, for functional connectivity of sensory and cognitively related RSNs. CONCLUSION: The network property alterations of functional connectivity in different consciousness levels suggest a whole-brain topological reorganization of the large-scale functional connectivity in patients with DOC.

Establishing an acquisition and processing protocol for resting state networks with a 1.5 T scanner: A case series in a middle-income country.

OBJECTIVE: The aim of this study was to characterize the capability of detection of the resting state networks (RSNs) with functional magnetic resonance imaging (fMRI) in healthy subjects using a 1.5T scanner in a middle-income country. MATERIALS AND METHODS: Ten subjects underwent a complete blood-oxygen-level dependent imaging (BOLD) acquisition on a 1.5T scanner. For the imaging analysis, we used the spatial independent component analysis (sICA). We designed a computer tool for 1.5 T (or above) scanners for imaging processing. We used it to separate and delineate the different components of the RSNs of the BOLD signal. The sICA was also used to differentiate the RSNs from noise artifact generated by breathing and cardiac cycles. RESULTS: For each subject, 20 independent components (IC) were computed from the sICA (a total of 200 ICs). From these ICs, a spatial pattern consistent with RSNs was identified in 161 (80.5%). From the 161, 131 (65.5%) were fit for study. The networks that were found in all subjects were: the default mode network, the right executive control network, the medial visual network, and the cerebellar network. In 90% of the subjects, the left executive control network and the sensory/motor network were observed. The occipital visual network was present in 80% of the subjects. In 39 (19.5%) of the images, no any neural network was identified. CONCLUSIONS: Reproduction and differentiation of the most representative RSNs was achieved using a 1.5T scanner acquisitions and sICA processing of BOLD imaging in healthy subjects.

Structural and functional connectivity of ascending reticular activating system in a patient with impaired consciousness after a cardiac arrest: A case report.

RATIONALE: Diffusion tensor imaging (DTI), diffusion tensor tractography (DTT), as well as resting-state-functional magnetic resonance imaging (rsfMRI) are promising methods for assessing patients with disorders of consciousness (DOCs). PATIENT CONCERNS: This work describes the main findings using DTI, DTT, and rsfMRI in a patient with a DOC secondary to an anoxic encephalopathy who had a fatal outcome. She was an 85-year-old woman who presented a cardiac arrest and underwent cardiopulmonary resuscitation for 20 minutes then returning to spontaneous circulation. After sedation withdrawal, 2 days after the event, she remained with a Glasgow Coma Scale score of 3/15 and with an absence of brainstem reflexes. DIAGNOSES: DOC secondary to an anoxic encephalopathy after cardiovascular resuscitation. INTERVENTIONS: A complete brain MRI scan was performed 72 hours after the initial event, including DTI, DTT, and rsfMRI. DTT demonstrated disruption of both ventral and dorsal tegmental tracts bilaterally. DTI showed a reduction of fractional anisotropic level in the mesencephalic nuclei. Moreover, changes in the number of fiber tracts were not evidenced in any portions of the ascending reticular activating system (ARAS). Finally, an increase in the anticorrelated and correlated association among the nuclei in the ARAS and the cortex was evidenced. OUTCOMES: Patient deceased. LESSONS: Neuroimaging demonstrated low FA values in the ARAS, destruction of dorsal and ventral tegmental tracts, as well as hyper-connective (highly correlated or anti-correlated) association among ARAS and cortical nuclei compared with 3 healthy control subjects.

Screen for Slit/Robo signaling in trunk neural cells reveals new players.

Slits ligands and their Robo receptors are involved in quite disparate cell signaling pathways that include axon guidance, cell proliferation, cell motility and angiogenesis. Neural crest cells emerge by delamination from neural cells in the dorsal neural tube, and give rise to various components of the peripheral nervous system in vertebrates. It is well established that these cells change from a non-migratory to a highly migratory state allowing them to reach distant regions before they differentiate. However, but the mechanism controlling this delamination and subsequent migration are still not fully understood. The repulsive Slit ligand family members, have been classified also as true tumor suppressor molecules. The present study explored in further detail what possible Slit/Robo signals are at play in the trunk neural cells and neural crest cells by carrying out a microarray after Slit2 gain of function in trunk neural tubes. We found that in addition to molecules known to be downstream of Slit/Robo signaling, there were a large set of molecules known to be important in maintaining cells in non-motile, epithelia phenotype. Furthermore, we found new molecules previously not associated with Slit/Robo signaling: cell proliferation markers, Ankyrins and RAB intracellular transporters. Our findings suggest that neural crest cells use and array of different Slit/Robo pathways during their transformation from non-motile to highly motile cells.

Completitud de inventarios rápidos de diversidad de mamíferos medianos y grandes en la Amazonía noroccidental colombiana / Completeness of rapid assessments of medium and large mammal diversity in the northwestern Amazon in Colombia

Las evaluaciones rápidas de biodiversidad son la fuente de información más común sobre biodiversidad en el noroccidente amazónico en Colombia debido a que los recursos y la logística son limitados. Estas evaluaciones son esenciales para tomar decisiones ambientales en esta área que ha sido impactada por la transformación de sus ecosistemas naturales. Diferentes evaluaciones locales rápidas con cámaras trampa de mamíferos medianos y grandes (MMG) se han realizado en el noroccidente Amazónico en Colombia, pero estas son difícilmente comparables. Nosotros recolectamos la información de 16 evaluaciones rápidas de MMG para proporcionar la primera lista de MMG del noroccidente amazónico en Colombia. Adicionalmente, evaluamos la precisión de cuatro estimadores (ICE, Chao 2, Jackknife 1 y Jackknife 2) y el esfuerzo mínimo de muestreo para la estimación de la riqueza de MMG en estudios locales en esa región. Reportamos 26 especies de MMG para la Amazonía colombiana (entre cinco y 13 especies por localidad), lo que es uns subestimación de la riqueza de MMG en la región. El mejor estimador para este tipo de estudios fue Jackknife 1, debido a su precisión y la baja influencia de singletons. Recomendamos un esfuerzo mínimo de muestreo de 350 cámaras trampa-día. Aunque las evaluaciones rápidas no proveen una estimación robusta de la riqueza de MMG, estas evaluaciones registran las especies más comunes (especies core) y la variación en su abundancia por localidad. Es necesario un mayor esfuerzo de muestreo para evaluar el efecto de la transformación del hábitat sobre los MMG, en especial sobre los parámetros poblacionales de las especies raras. (AU)

The bat assemblages (Mammalia: Chiroptera) of the Serranía de La Lindosa are diverse and heterogeneous / Los ensamblajes de murciélagos (mammalia: chiroptera) de la serranía de la lindosa son diversos y heterogéneos

RESUMEN La Serranía de La Lindosa es una formación geomorfológica que presenta heterogeneidad en sus coberturas vegetales. Esta zona se encuentra en una situación contradictoria debido a que presenta una elevada biodiversidad, sin embargo, es uno de los actuales focos de deforestación más grandes de Colombia. A pesar de que se espera una alta diversidad de murciélagos en La Lindosa existe poca información publicada sobre este grupo. Este trabajo presenta los resultados de inventarios de murciélagos realizados durante cinco años en la Serranía de la Lindosa. Se compara la diversidad (riqueza, composición y estructura) de los ensamblajes de murciélagos en dos tipos principales de cobertura vegetal, los bosques húmedos y las sabanas casmófitas. Los inventarios recogen información de 735 murciélagos capturados, correspondientes a 46 especies. De estas, 14 especies se encontraron solamente en sabanas casmófitas, 11 en bosques húmedos y 19 en los dos tipos de vegetación. De esta manera, se evidencia una alta complementariedad en la composición de especies de murciélagos entre los dos tipos de vegetación. Adicionalmente, la estructura de los ensamblajes de murciélagos varió entre los dos ambientes. La abundancia entre las especies es más homogénea en las sabanas casmófitas con un mayor número de especies raras comparado con los bosques húmedos. En general, la alta diversidad de murciélagos de la Serranía de La Lindosa puede estar relacionada con la heterogeneidad en la vegetación, la presencia de diferentes tipos de cuevas, y la historia evolutiva de las especies de murciélagos asociados a la Región Guayana.

ABSTRACT The Serranía La Lindosa is a geomorphological formation with land cover heterogeneity. This area faces a contradictory situation because it has high biodiversity and provides several ecosystem services, and yet it is one of the current largest deforestation sites in Colombia. Bats is a taxonomic group with high expected diversity in La Lindosa, but there is little published information about this group. This paper presents the results of bat inventories carried out during five years in the Lindosa mountain range. Additionally, diversity is compared in terms of species richness, composition, and structure of bat assemblies in two main types ofvegetation cover evident in the area, which are humid forests and casmophytic savannas. Inventories collected information on 735 captured bats, corresponding to 46 species. Of these, 14 species were found only in casmophytic savannas, 11 in humid forests, and 19 in both types of vegetation. Thus, there is high complementarity in bat species composition between the two vegetation types. Additionally, the structure of bat assemblies varied between the two environments, with a proportional distribution of species abundance more homogeneous in casmophytic savannas than in forests. Besides, a higher number of rare species was found in casmophytic savannas. In general, the high diversity of bats of the Serranía de La Lindosa could be associated with vegetation heterogeneity, presence of different cave types and evolutionary history of bat species associated with the Guayana Region.

Characterization of the trunk neural crest in the bamboo shark, Chiloscyllium punctatum.

The neural crest is a population of mesenchymal cells that after migrating from the neural tube gives rise to structure and cell types: the jaw, part of the peripheral ganglia, and melanocytes. Although much is known about neural crest development in jawed vertebrates, a clear picture of trunk neural crest development for elasmobranchs is yet to be developed. Here we present a detailed study of trunk neural crest development in the bamboo shark, Chiloscyllium punctatum. Vital labeling with dioctadecyl tetramethylindocarbocyanine perchlorate (DiI) and in situ hybridization using cloned Sox8 and Sox9 probes demonstrated that trunk neural crest cells follow a pattern similar to the migratory paths already described in zebrafish and amphibians. We found shark trunk neural crest along the rostral side of the somites, the ventromedial pathway, the branchial arches, the gut, the sensory ganglia, and the nerves. Interestingly, C. punctatum Sox8 and Sox9 sequences aligned with vertebrate SoxE genes, but appeared to be more ancient than the corresponding vertebrate paralogs. The expression of these two SoxE genes in trunk neural crest cells, especially Sox9, matched the Sox10 migratory patterns observed in teleosts. Also of interest, we observed DiI cells and Sox9 labeling along the lateral line, suggesting that in C. punctatum, glial cells in the lateral line are likely of neural crest origin. Although this has been observed in other vertebrates, we are the first to show that the pattern is present in cartilaginous fishes. These findings demonstrate that trunk neural crest cell development in C. punctatum follows the same highly conserved migratory pattern observed in jawed vertebrates.