Kidins220 sets the threshold for survival of neural stem cells and progenitors to sustain adult neurogenesis.

In the adult mammalian brain, neural stem cells (NSCs) located in highly restricted niches sustain the generation of new neurons that integrate into existing circuits. A reduction in adult neurogenesis is linked to ageing and neurodegeneration, whereas dysregulation of proliferation and survival of NSCs have been hypothesized to be at the origin of glioma. Thus, unravelling the molecular underpinnings of the regulated activation that NSCs must undergo to proliferate and generate new progeny is of considerable relevance. Current research has identified cues promoting or restraining NSCs activation. Yet, whether NSCs depend on external signals to survive or if intrinsic factors establish a threshold for sustaining their viability remains elusive, even if this knowledge could involve potential for devising novel therapeutic strategies. Kidins220 (Kinase D-interacting substrate of 220 kDa) is an essential effector of crucial pathways for neuronal survival and differentiation. It is dramatically altered in cancer and in neurological and neurodegenerative disorders, emerging as a regulatory molecule with important functions in human disease. Herein, we discover severe neurogenic deficits and hippocampal-based spatial memory defects accompanied by increased neuroblast death and high loss of newly formed neurons in Kidins220 deficient mice. Mechanistically, we demonstrate that Kidins220-dependent activation of AKT in response to EGF restraints GSK3 activity preventing NSCs apoptosis. We also show that NSCs with Kidins220 can survive with lower concentrations of EGF than the ones lacking this molecule. Hence, Kidins220 levels set a molecular threshold for survival in response to mitogens, allowing adult NSCs growth and expansion. Our study identifies Kidins220 as a key player for sensing the availability of growth factors to sustain adult neurogenesis, uncovering a molecular link that may help paving the way towards neurorepair.

Role of cytokines, chemokines, C3a, and mannose-binding lectin in the evolution of the chikungunya infection.

The pathogenesis of the severity of chikungunya infection is not yet fully understood. OBJECTIVE: To assess the role of the cytokines/chemokines and system of complement in the evolution of chikungunya infection. METHODS: In both acute and chronic phases, we measured the serum levels of 12 cytokines/chemokines and two complement mediators: mannose-binding lectin (MBL) and C3a, in 83 patients with chikungunya infection and ten healthy controls. RESULTS: During the acute phase, 75.9% of the patients developed musculoskeletal disorders, and in 37.7% of them, these disorders persisted until the chronic phase. In general, patients had higher levels of cytokines than healthy controls, with significant differences for IFN-γ, IL-6, IL-8, IL-10, and MIP-1. Most cytokines exhibited a downward trend during the chronic phase. However, only IL-10, and MIP-1 levels were significantly lower in the chronic phase. Additionally, these levels never decreased to concentrations found in healthy controls. Moreover, MBL levels were significantly higher in the acute phase compared with the chronic phase. C3a levels were significantly higher in patients with musculoskeletal disorder compared with patients without it, in both acute-phase 118.2 (66.5-252.9), and chronic phase 68.5 (64.4-71.3), P < 0.001. Interestingly, C3a levels were significantly higher when patients had a severe disease version. Besides, in the acute phase, C3a levels were higher in patients that suffer arthritis as opposed to when they suffer arthralgia, 194.3 (69.5-282.2), and 70.9 (62.4-198.8), P = 0.013, respectively. CONCLUSIONS: Our results showed an immunological response that persisted until the chronic phase and the role of the complement system in the severity of the disease.

Evaluation of Platelet Rich Fibrin Obtained Using Different Centrifugation Parameters as a Tool for Regenerative Medicine.

BACKGROUND: Platelet-rich fibrin (PRF) is a biomaterial widely used in the field of regenerative medicine. The purpose of this work was to analyze the structure and biomolecular characteristics of PRF through nine centrifugation parameters (CP) for its preparation, using a pool of blood samples of five volunteers. METHODS: The PRF obtained was analyzed by morphological and histological characteristics, as well as electronic and atomic force microscopy and growth factors determinations. RESULTS: A longer time of centrifugation showed taller clots and denser mesh fibrin in comparison with a short time (p < 0.05). The protocols with higher speed of centrifugation showed higher levels of PDGF-BB and VEGF. Higher levels of TGFß1 were found in protocols with a shorter centrifuge time. The mean platelet count (916.05 ± 23.73 cells x 103 cells x cm3) and its roughness (Ra) (616.5 ± 45.2 nm) did not show significant differences between different CP (p > 0.05). A significant correlation between fibrin density and levels of PDGF (r = 0.57) and VEGF (r = 0.52) was found. Additionally, the size of the clot had a significant correlation (r = -0.47) with TGFß1 levels. CONCLUSIONS: Different centrifugation parameters to obtain PRF have been reported. These results indicate that changes in the conditions to obtain PRF have a significant impact on their fibrin structure, cellular distribution, and biomolecular content, which can be decisive for its choice in the different clinical applications to be used. It is necessary to use a standardized centrifuge and protocol to guarantee high-quality PRF and clinical outcomes with less variability.

Minireview: Epidemiological impact of arboviral diseases in Latin American countries, arbovirus-vector interactions and control strategies.

Mosquitoes are the most crucial insects in public health due to their vector capacity and competence to transmit pathogens, including arboviruses, bacterias and parasites. Re-emerging and emerging arboviral diseases, such as yellow fever virus (YFV), dengue virus (DENV), zika virus (ZIKV), and chikungunya virus (CHIKV), constitute one of the most critical health public concerns in Latin America. These diseases present a significant incidence within the human settlements increasing morbidity and mortality events. Likewise, among the different genus of mosquito vectors of arboviruses, those of the most significant medical importance corresponds to Aedes and Culex. In Latin America, the mosquito vector species of YFV, DENV, ZIKV, and CHIKV are mainly Aedes aegypti and Ae. Albopictus. Ae. aegypti is recognized as the primary vector in urban environments, whereas Ae. albopictus, recently introduced in the Americas, is more prone to rural settings. This minireview focuses on what is known about the epidemiological impact of mosquito-borne diseases in Latin American countries, with particular emphasis on YFV, DENV, ZIKV and CHIKV, vector mosquitoes, geographic distribution, and vector-arbovirus interactions. Besides, it was analyzed how climate change and social factors have influenced the spread of arboviruses and the control strategies developed against mosquitoes in this continent.

Fístulas arteriovenosas pulmonares en un paciente pediátrico: un reporte de caso / Pulmonary arteriovenous fistulas in a pediatric patient: a case report

Las fístulas arteriovenosas pulmonares son malformaciones congénitas dadas por la comunicación directa anómala entre arterias y venas, con una incidencia mundial de 2-3 : 100 000 habitantes. La presentación es, en general, única, asintomática, y aparecen en forma incidental como hallazgo imagenológico en la adultez, y su tratamiento de elección es la embolización endovascular.Se describe la inusual presentación clínica en una paciente de 10 años, que ingresó por disnea, tos, cianosis central y cefalea. Se encontró hipoxemia persistente, hipocratismo digital, nódulos parahiliares pulmonares, gases arteriales con gradiente alvéolo-arterial aumentado. La tomografía axial computarizada de tórax de alta resolución confirmó la presencia de una malformación arteriovenosa pulmonar en la región parahiliar derecha, la cual no se asociaba con la enfermedad de Rendu-Osler-Weber. La paciente fue tratada con embolización endovascular transcutánea. Tras 1,5 años de seguimiento, no hubo recaídas. Son pocos los casos reportados de estas fístulas en la edad pediátrica

Pulmonary arteriovenous fistulas are congenital malformations due to anomalous direct communication between arteries and veins; the incidence is 2-3 : 100,000 inhabitants. This condition is usually asymptomatic and incidentally appearing in adult imaging findings. Transcutaneous endovascular embolization is the technique of choice for treatment. The unusual presentation in a 10-year-old patient is described; she was presented to the Emergency Department with dyspnea, cough, central cyanosis and headache. The examination revealed persistent hypoxemia and digital clubbing; chest X-ray with images suggestive of parahilar nodules, arterial blood gases with increased alveolar arterial gradient. The high resolution computed tomography of the thorax revealed pulmonary arteriovenous malformation in the right parahilar region not associated with Rendu-Osler-Weber disease. The patient was treated with transcutaneous endovascular embolization, and after a year and a half of follow-up there were no relapses. There are few reported cases of pulmonary arteriovenous fistulas in the pediatric age.

[Pulmonary arteriovenous fistulas in a pediatric patient: a case report]. / Fístulas arteriovenosas pulmonares en un paciente pediátrico: un reporte de caso.

Pulmonary arteriovenous fistulas are congenital malformations due to anomalous direct communication between arteries and veins; the incidence is 2-3 : 100,000 inhabitants. This condition is usually asymptomatic and incidentally appearing in adult imaging findings. Transcutaneous endovascular embolization is the technique of choice for treatment. The unusual presentation in a 10-year-old patient is described; she was presented to the Emergency Department with dyspnea, cough, central cyanosis and digital clubbing; chest X-ray with images suggestive of parahilar nodules, arterial blood gases with increased alveolar arterial gradient. The high resolution computed tomography of the thorax revealed pulmonary arteriovenous malformation in the right parahilar region not associated with Rendu-Osler- Weber disease. The patient was treated with transcutaneous endovascular embolization, and after a year and a half of follow-up there were no relapses. There are few reported cases of pulmonary arteriovenous fistulas in the pediatric age.

Las fístulas arteriovenosas pulmonares son malformaciones congénitas dadas por la comunicación directa anómala entre arterias y venas, con una incidencia mundial de 2-3 : 100 000 habitantes. La presentación es, en general, única, asintomática, y aparecen en forma incidental como hallazgo imagenológico en la adultez, y su tratamiento de elección es la embolización endovascular. Se describe la inusual presentación clínica en una paciente de 10 años, que ingresó por disnea, tos, cianosis central y cefalea. Se encontró hipoxemia persistente, hipocratismo digital, nódulos parahiliares pulmonares, gases arteriales con gradiente alvéolo-arterial aumentado. La tomografía axial computarizada de tórax de alta resolución confirmó la presencia de una malformación arteriovenosa pulmonar en la región parahiliar derecha, la cual no se asociaba con la enfermedad de Rendu-Osler-Weber. La paciente fue tratada con embolización endovascular transcutánea. Tras 1,5 años de seguimiento, no hubo recaídas. Son pocos los casos reportados de estas fístulas en la edad pediátrica.

Ingeniería Tisular Para Regeneración Nerviosa: Una Revisión / Tissue Engineering For Nervous Regeneration: A Review

Resumen Introducción: Este artículo presenta avances de la medicina regenerativa y la ingeniería de tejidos orientados a la regeneración de neuronas, de axones y nervios. Revisamos las técnicas que existen actualmente, las más utilizas o prometedoras, en la búsqueda de avances para regenerar este tipo de tejidos. Objetivo: Con esta revisión queremos describir el conocimiento actual sobre la medicina regenerativa y la ingeniería de tejidos orientados a la reparación de tejidos nerviosos. Metodología: Para desarrollar esta revisión se realizó una búsqueda de artículos entre los años 2007 y el 2018, la búsqueda se restringió a los artículos que incluyeran dentro de sus palabras clave; Ingeniería tisular, Enfermedades Neurodegenerativas, Medicina regenerativa, Regeneración axonal, Regeneración neuronal, Regeneración tisular. Con el fin de seleccionar los artículos más adecuados, se realizó una búsqueda exhaustiva en bases de datos como Springer, Medline Ebsco y Science direct. Conclusiones: Se mencionan técnicas como implantación de injertos, terapia celular y terapia molecular e implantación de andamios 3D para regeneración de neuronas, axones y nervios; a partir de esta revisión pudimos observar que estas técnicas en su mayoría funcionan mejor cuando se combinan, aprovechando las ventajas de cada una para promover la regeneración de los diferentes tejidos nerviosos.

Introduction: This article presents advances in regenerative medicine aimed at the regeneration of nervous and neuronal tissue, focusing on regeneration of neurons, axons and nerve regeneration. We will review the techniques that currently exist, the most used or promising, in the search of advances to regenerate this type of tissues. Objective: With this review we want to describe the current knowledge about regenerative medicine and tissue engineering oriented to nerve tissue repair. Methodology: To carry out this review, a search of articles was carried out between 2007 and 2018, the search was restricted to the articles that they included within their keywords; Tissue Engineering, Neurodegenerative Diseases, Regenerative Medicine, Axonal Regeneration, Neuronal Regeneration, Tissue Regeneration. We will mention about techniques such as implantation. Conclusions: with this review we could observe that most of the mentioned techniques work better when combined, taking advantage of each one to promote a greater regeneration of the different tissues.

Platelet-rich plasma, a powerful tool in dermatology.

Platelet-rich plasma (PRP), a platelet concentrate contained in a small volume of plasma, has become a promising option in the last decade to treat different diseases related to the skin due to its high concentration of growth factors. When it is of autologous origin, it decreases the probability of suffering adverse reactions and transfusion-transmitted infections, thus it is an optimal and safe therapy for the patient. PRP has been used in the treatment of several dermatological conditions such as acne, alopecia, and skin ulcers. Its use has also extended to other skin conditions such as melasma, hyperpigmentation, and burns, where it stimulates tissue repair and regeneration. The purpose of this article is to review the management and treatment of different dermatological alterations with PRP. Although there are a variety of studies that support the use of PRP, more research is needed to standardise the protocols for obtaining, processing, and applying it as well as understanding the biological and molecular bases of its functioning.

Toll-Like Receptor 4 Mediates Hemorrhagic Transformation After Delayed Tissue Plasminogen Activator Administration in In Situ Thromboembolic Stroke.

BACKGROUND AND PURPOSE: Hemorrhagic transformation is the main complication of revascularization therapies after stroke. Toll-like receptor 4 (TLR4) is implicated in cerebral damage and inflammation in stroke. This study was designed to determine the role of TLR4 in hemorrhagic transformation development after tissue plasminogen activator (tPA) administration. METHODS: Mice expressing (TLR4+/+) or lacking functional TLR4 (TLR4-/-) were subjected to middle cerebral artery occlusion using an in situ thromboembolic model by thrombin injection into the middle cerebral artery, and tPA (10 mg/kg) was administered 20 minutes or 3 hours after ischemia. Infarct size, hemorrhages, IgG extravasation, matrix metalloproteinase 9 expression, and neutrophil infiltration were assessed 24 hours after ischemia. RESULTS: In TLR4+/+, early reperfusion (tPA at 20 minutes) resulted infarct volume, whereas late recanalization (tPA at 3 hours) did not modify lesion size and increased the rate of the most severe hemorrhages. In TLR4-/- mice, both early and late reperfusion did not modify lesion size. Importantly, late tPA administration did not result in worse hemorrhages and in an increased bleeding area as occurred in TLR4+/+ group. In TLR4-/- animals, late reperfusion produced a lesser increase in matrix metalloproteinase 9 expression when compared with TLR4+/+ animals. CONCLUSIONS: Our results demonstrate TLR4 involvement in hemorrhagic transformation induced by delayed tPA administration, very likely by increasing matrix metalloproteinase 9 expression.