miR-137 confers robustness to the territorial restriction of the neural plate border.

The neural plate border (NPB) of vertebrate embryos is segregated from the neural plate (NP) and epidermal regions, and comprises an intermingled group of progenitors with multiple fate potential. Recent studies have shown that, during the gastrula stage, TFAP2A acts as a pioneer factor in remodeling the epigenetic landscape required to activate components of the NPB induction program. Here, we show that chick Tfap2a has two highly conserved binding sites for miR-137, and both display a reciprocal expression pattern at the NPB and NP, respectively. In addition, ectopic miR-137 expression reduced TFAP2A, whereas its functional inhibition expanded their territorial distribution overlapping with PAX7. Furthermore, we demonstrate that loss of the de novo DNA methyltransferase DNMT3A expanded miR-137 expression to the NPB. Bisulfite sequencing revealed a markedly elevated presence of non-canonical CpH methylation within the miR-137 promoter region when comparing NPB and NP samples. Our findings show that miR-137 contributes to the robustness of NPB territorial restriction in vertebrate development.

Increased glutamatergic neurotransmission between the retinohypothalamic tract and the suprachiasmatic nucleus of old mice.

Circadian rhythms synchronize to light through the retinohypothalamic tract (RHT), which is a bundle of axons coming from melanopsin retinal ganglion cells, whose synaptic terminals release glutamate to the ventral suprachiasmatic nucleus (SCN). Activation of AMPA-kainate and NMDA postsynaptic receptors elicits the increase in intracellular calcium required for triggering the signaling cascade that ends in phase shifts. During aging, there is a decline in the synchronization of circadian rhythms to light. With electrophysiological (whole-cell patch-clamp) and immunohistochemical assays, in this work, we studied pre- and postsynaptic properties between the RHT and ventral SCN neurons in young adult (P90-120) and old (P540-650) C57BL/6J mice. Incremental stimulation intensities (applied on the optic chiasm) induced much lesser AMPA-kainate postsynaptic responses in old animals, implying a lower recruitment of RHT fibers. Conversely, a higher proportion of old SCN neurons exhibited synaptic facilitation, and variance-mean analysis indicated an increase in the probability of release in RHT terminals. Moreover, both spontaneous and miniature postsynaptic events displayed larger amplitudes in neurons from aged mice, whereas analysis of the NMDA and AMPA-kainate components (evoked by RHT electrical stimulation) disclosed no difference between the two ages studied. Immunohistochemistry revealed a bigger size in the puncta of vGluT2, GluN2B, and GluN2A of elderly animals, and the number of immunopositive particles was increased, but that of PSD-95 was reduced. All these synaptic adaptations could be part of compensatory mechanisms in the glutamatergic signaling to ameliorate the loss of RHT terminals in old animals.

Pigmented neurofibroma with hypertrichosis.

BACKGROUND: Pigmented (or melanocytic) neurofibroma (PN) constitutes only 1% of cases and is considered a rare variant of neurofibroma containing melanin-producing cells. In addition, the association of PN with hypertrichosis is infrequent. CASE REPORT: We describe the case of an 8-year-old male with a neurofibromatosis type 1 (NF1) diagnosis, who presented a light brown hyperpigmented plaque, smooth and well-demarcated, and hypertrichosis on the left thigh. The skin biopsy showed characteristics of neurofibroma; however, in the deep portion of the lesion, melanin deposits positive for S100, Melan-A, and HMB45 were observed, thus establishing the diagnosis of pigmented neurofibroma. CONCLUSIONS: Although PN is a rare subtype of neurofibroma, it is considered a chronically progressive benign tumor containing melanin-producing cells. These lesions can appear alone or in association with neurofibromatosis. Since this is a tumor that can be confused with other skin lesions, biopsy analysis is essential to differentiate it from other pigmented skin tumors, such as melanocytic schwannoma, dermatofibrosarcoma protuberans, neurocristic hamartoma, or neuronevus. Surveillance is part of the treatment, and surgical resection is sometimes performed.

INTRODUCCIÓN: El neurofibroma pigmentado (NP) o melanocítico constituye solamente el 1% de los casos y se considera como una variante rara del neurofibroma que contiene células productoras de melanina. Además, la asociación de NP con hipertricosis es muy rara. CASO CLÍNICO: Se describe el caso de un paciente de sexo masculino de 8 años 2 meses de edad con diagnóstico de neurofibromatosis tipo 1 (NF1), quien presentaba en la cara anterior del muslo izquierdo una placa hiperpigmentada de color café claro, bien delimitada y de consistencia suave, e hipertricosis. La biopsia de piel presentó cambios característicos de neurofibroma; sin embargo, en la porción profunda de la lesión se observaron depósitos de melanina positivos para S100, Melan-A y HMB45, con lo que se estableció el diagnóstico de neurofibroma pigmentado. CONCLUSIONES: Aunque el NP es un subtipo raro del neurofibroma, se considera que es un tumor benigno de evolución crónica de células productoras de melanina. Estas lesiones aparecen en solitario o asociadas con neurofibromatosis. Dado que es un tumor que puede confundirse con otras lesiones cutáneas, es fundamental el análisis de la biopsia para diferenciarlo de otros tumores cutáneos pigmentados, como el schwanoma melanocítico, dermatofibrosarcoma protuberans, hamartoma neurocrístico o neuronevus. La vigilancia es parte del tratamiento y, en ocasiones, se lleva a cabo la resección quirúrgica.

Symptomatic subgemmal neurogenous plaque in patients with COVID-19: Is there an association?

BACKGROUND: Subgemmal neurogenous plaques (SNP) are composed of neural structures found in the posterolateral portion of the tongue, rarely biopsied as most of them are asymptomatic or eventually only clinically managed. We aimed to investigate a case series of possible correlation of symptomatic subgemmal neurogenous plaque (SNP) with coronavirus disease 2019 (COVID-19). METHODS: Eleven formalin-fixed paraffin-embedded cases from patients with previous confirmed COVID-19 (by RT-PCR) were retrieved from two pathology files. Histological sections were morphologically studied, and then submitted to immunohistochemical reactions against S-100 and neurofilament proteins, neuron-specific enolase, Glial fibrillary acidic protein (GFAP), synaptophysin, CD56, Ki67, cytokeratins (7, 8-18, 19, 20), nucleocapsid and spike proteins (SARS-CoV-1; and -2) and epithelial membrane antigen (EMA) antibodies. Clinical data were retrieved from the patients' medical files, including the symptoms and the complete history of the progression of the disease. RESULTS: The patients who had COVID-19 included in this study experienced painful lesions in the tongue that corresponded to prominent or altered SNP. Microscopically, neural structures were positive for S-100, GFAP and neurofilament protein. And the cellular proliferative index (by Ki-67) was very low. CONCLUSION: Thus, based on the current results, we hypothesize that symptomatic SNP may be a late manifestation of COVID-19 infection.

Automatic dental biofilm detection based on deep learning.

AIM: To estimate the automated biofilm detection capacity of the U-Net neural network on tooth images. MATERIALS AND METHODS: Two datasets of intra-oral photographs taken in the frontal and lateral views of permanent and deciduous dentitions were employed. The first dataset consisted of 96 photographs taken before and after applying a disclosing agent and was used to validate the domain's expert biofilm annotation (intra-class correlation coefficient = .93). The second dataset comprised 480 photos, with or without orthodontic appliances, and without disclosing agents, and was used to train the neural network to segment the biofilm. Dental biofilm labelled by the dentist (without disclosing agents) was considered the ground truth. Segmentation performance was measured using accuracy, F1 score, sensitivity, and specificity. RESULTS: The U-Net model achieved an accuracy of 91.8%, F1 score of 60.6%, specificity of 94.4%, and sensitivity of 67.2%. The accuracy was higher in the presence of orthodontic appliances (92.6%). CONCLUSIONS: Visually segmenting dental biofilm employing a U-Net is feasible and can assist professionals and patients in identifying dental biofilm, thus improving oral hygiene and health.

A blinking focal pattern of re-entrant activity in the avian tectum.

Re-entrant connections are inherent to nervous system organization; however, a comprehensive understanding of their operation is still lacking. In birds, topographically organized re-entrant signals, carried by axons from the nucleus-isthmi-parvocellularis (Ipc), are distinctly recorded as bursting discharges across the optic tectum (TeO). Here, we used up to 48 microelectrodes regularly spaced on the superficial tectal layers of anesthetized pigeons to characterize the spatial-temporal pattern of this axonal re-entrant activity in response to different visual stimulation. We found that a brief luminous spot triggered repetitive waves of bursting discharges that, appearing from initial sources, propagated horizontally to areas representing up to 28° of visual space, widely exceeding the area activated by the retinal fibers. In response to visual motion, successive burst waves started along and around the stimulated tectal path, tracking the stimulus in discontinuous steps. When two stimuli were presented, the burst-wave sources alternated between the activated tectal loci, as if only one source could be active at any given time. Because these re-entrant signals boost the retinal input to higher visual areas, their peculiar dynamics mimic a blinking "spotlight," similar to the internal searching mechanism classically used to explain spatial attention. Tectal re-entry from Ipc is thus highly structured and intrinsically discontinuous, and higher tectofugal areas, which lack retinotopic organization, will thus receive incoming visual activity in a sequential and piecemeal fashion. We anticipate that analogous re-entrant patterns, perhaps hidden in less bi-dimensionally organized topographies, may organize the flow of neural activity in other parts of the brain as well.

FGFR1 is an important prognostic factor in oral leukoplakia and tongue squamous cell carcinoma.

BACKGROUND: Fibroblast growth factor receptor 1 is a potential prognostic factor for tongue squamous cell carcinoma and is associated with oral epithelial dysplasia grade in oral leukoplakia. METHODS: Thirty cases of tongue squamous cell carcinoma and 30 cases of oral leukoplakia were analyzed. Fibroblast growth factor receptor 1 and phosphorylated Akt protein expression were analyzed by immunohistochemistry and quantified using a digital algorithm. Fibroblast growth factor receptor 1 gene amplification was analyzed by fluorescent in situ hybridization in the tongue squamous cell carcinoma cases. RESULTS: Clinical appearance and dysplasia grade were correlated with oral leukoplakia malignant transformation. Oral leukoplakia cases presenting high fibroblast growth factor receptor 1 expression showed a higher risk of malignant transformation (p = 0.016, HR: 7.3, 95% CI: 1.4-37.4). Phosphorylated Akt showed faint to no expression in oral leukoplakia, which did not correlate with dysplasia grade or malignant transformation. High expression of fibroblast growth factor receptor 1 and phosohorylated Akt were associated with poor overall survival and disease-free survival in tongue squamous cell carcinoma, although only fibroblast growth factor receptor 1 expression was significantly associated with poor overall survival (p = 0.024; HR: 4.9, 95% CI: 1.2-19.9). Cases presenting double fibroblast growth factor receptor 1/phosphorylated Akt overexpression (n = 8) showed markedly impaired overall survival (p = 0.020; HR: 6.4, 95% CI: 1.3-31.1) and disease-free survival (p = 0.001, HR: 13.0, 95% CI: 3.0-55.7). Fibroblast growth factor receptor 1 amplification was observed in 16.6% of tongue squamous cell carcinoma cases, being correlated with vascular and neural invasion (p = 0.001 and 0.017, respectively), but not with fibroblast growth factor receptor 1 protein expression, overall survival, or disease-free survival. CONCLUSION: Fibroblast growth factor receptor 1 protein expression is an important prognostic factor in oral leukoplakia and tongue squamous cell carcinoma.

The human amniotic epithelium confers a bias to differentiate toward the neuroectoderm lineage in human embryonic stem cells.

Human embryonic stem cells (hESCs) derive from the epiblast and have pluripotent potential. To maintain the conventional conditions of the pluripotent potential in an undifferentiated state, inactivated mouse embryonic fibroblast (iMEF) is used as a feeder layer. However, it has been suggested that hESC under this conventional condition (hESC-iMEF) is an artifact that does not correspond to the in vitro counterpart of the human epiblast. Our previous studies demonstrated the use of an alternative feeder layer of human amniotic epithelial cells (hAECs) to derive and maintain hESC. We wondered if the hESC-hAEC culture could represent a different pluripotent stage than that of naïve or primed conventional conditions, simulating the stage in which the amniotic epithelium derives from the epiblast during peri-implantation. Like the conventional primed hESC-iMEF, hESC-hAEC has the same levels of expression as the 'pluripotency core' and does not express markers of naïve pluripotency. However, it presents a downregulation of HOX genes and genes associated with the endoderm and mesoderm, and it exhibits an increase in the expression of ectoderm lineage genes, specifically in the anterior neuroectoderm. Transcriptome analysis showed in hESC-hAEC an upregulated signature of genes coding for transcription factors involved in neural induction and forebrain development, and the ability to differentiate into a neural lineage was superior in comparison with conventional hESC-iMEF. We propose that the interaction of hESC with hAEC confers hESC a biased potential that resembles the anteriorized epiblast, which is predisposed to form the neural ectoderm.

Diagnóstico, manejo y tratamiento actual del mielomeningocele fetal / Current diagnosis, management and treatment of fetal myelomeningocele

Introducción: El mielomeningocele fetal, es la extrusión de la médula espinal que ocurre por un cierre incompleto del neuróporo caudal, lo cual expone la placa neural al trauma mecáni-co y químico de la pared uterina y líquido amniótico respectivamente, con graves secuelas. La detección prenatal innovó el diagnóstico y con ello la reparación intra útero ha mejora-do estrategias del tratamiento, generando opciones de atención en aquellas pacientes que cumplen con los criterios de selección para cirugía prenatal. Objetivo: Presentar una revisión bibliográfica sobre diagnóstico, manejo y tratamiento del mielomeningocele fetal y ofrecer a la comunidad científica una herramienta de consulta para mejorar los conocimientos del tema y alternativas de tratamiento oportuno para los fetos con esta malformación.Material y Métodos: Se trata de un estudio de revisión sistemática sin metaanálisis, realiza-do en base a las recomendaciones PRISMA. La búsqueda de información se estructuró bajo el sistema PICO. Las búsquedas se realizaron en Pubmed, Tripdatabase y Pubmed Central; seleccionando artículos publicados durante los últimos diez años en inglés o español, sobre diagnóstico, manejo y tratamiento del mielomeningocele fetal. Resultados: 120 artículos cumplieron con criterios de búsqueda, de los cuáles fueron ele-gibles 42, con información relevante para determinar el diagnóstico, manejo y tratamiento actual del mielomeningocele fetal a través de procedimientos innovadores.Discusión: Los defectos del tubo neural aparecen como consecuencia de una alteración del proceso de neurulación entre el día 21-28 después de la concepción. El mielomeningocele fetal es considerado el defecto congénito no letal más común del SNC. Se caracteriza por la protrusión de las meninges y la médula espinal con daño neurológico permanente. Por ello el diagnóstico y manejo oportuno de esta patología, han permitido que la cirugía fetal intra útero se considere el método óptimo, mejorando la hernia del rombencéfalo, reduciendo la necesidad de una derivación ventricular y manteniendo la motricidad inferior, así como la función neuronal, vesical y gastrointestinal, mejorando la calidad de vida del paciente afecto por esta patología

Introduction: Fetal myelomeningocele is spinal cord extrusion that occurs due to the caudal neuropore incomplete closure, which exposes the neural plate to mechanical and chemical trauma to the uterus wall and amniotic fluid respectively, with serious sequelae. Prenatal detection innovated the diagnosis and with this intra-uterine repair has improved treatment strategies, generating care options in those patients who comply the selection criteria for prenatal surgery.Objective: Submit a bibliographic review on the diagnosis, management and treatment of fetal myelomeningocele and to offer the scientific community a consultation tool to improve knowledge of the subject and timely treatment alternatives for fetuses with this malformation.Materials and Methods: This is a systematic review study without meta-analysis, based on the PRISMA recommendations. The information search was structured under the PICO sys-tem. The searches were carried out in Pubmed, Tripdatabase and Pubmed Central; selecting articles published during the last ten years in English or Spanish, on diagnosis, management and treatment of fetal myelomeningocele.Results: 120 articles met the search criteria, of which 42 were eligible, with relevant informa-tion for determining the current diagnosis, management and treatment of fetal myelomenin-gocele through innovative procedures.Discussion: Neural tube defects appear as a consequence of an alteration of the neurula-tion process between days 21-28 after conception. MMCf is considered the most common non-fatal congenital defect of the CNS. It is characterized by protrusion of the meninges and spinal cord with permanent neurological damage. For this reason, the diagnosis and timely management of this pathology have allowed intra utero fetal surgery to be considered the optimal method, improving rhombencephalon hernia, reducing the need for a ventricular shunt and maintaining the lower motor skills, as well as neuronal, bladder and gastrointestinal function, improving the quality of life of the patient affected by this pathology.

Modeling Early Neural Crest Development via Induction from hiPSC-Derived Neural Plate Border-like Cells.

Neural crest cells (NCCs) are a multipotent and transient cell population that gives rise to many important tissues during human embryogenesis. Disturbances that occur during NCCs development may lead to numerous types of diseases and syndromes, which are called neurocristopathies. NCCs in vitro modeling enables the access to cellular, genetic, and biochemical information about the neural crest development and its derivatives. By using cells derived from patients with neurocristopathies it is possible to study the cellular and genetic mechanisms behind each disease in a specific and trustworthy manner, as well as to contribute to the development of prospective treatments. Here, we describe a protocol of 19 days, capable of efficiently generating NCCs from human induced pluripotent stem cells (hiPSCs). This differentiation process recapitulates the intermediate stage of neural plate border-like cells (NBCs), the epithelial to mesenchymal transition (EMT), and enables further generation of NCCs derivatives, such as Schwann cells, smooth muscle cells, melanocytes, peripheral neurons, adipocytes, osteoblasts, and chondrocytes.

Distinct Effects of the Hippocampal Transplantation of Neural and Mesenchymal Stem Cells in a Transgenic Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a severe disabling condition with no cure currently available, which accounts for 60-70% of all dementia cases worldwide. Therefore, the investigation of possible therapeutic strategies for AD is necessary. To this end, animal models corresponding to the main aspects of AD in humans have been widely used. Similar to AD patients, the double transgenic APPswe/PS1dE9 (APP/PS1) mice show cognitive deficits, hyperlocomotion, amyloid-ß (Αß) plaques in the cortex and hippocampus, and exacerbated inflammatory responses. Recent studies have shown that these neuropathological features could be reversed by stem cell transplantation. However, the effects induced by neural (NSC) and mesenchymal (MSC) stem cells has never been compared in an AD animal model. Therefore, the present study aimed to investigate whether transplantation of NSC or MSC into the hippocampus of APP/PS1 mice reverses AD-induced pathological alterations, evaluated by the locomotor activity (open field test), short- and long-term memory (object recognition) tests, Αß plaques (6-E10), microglia distribution (Iba-1), M1 (iNOS) and M2 (ARG-1) microglial phenotype frequencies. NSC and MSC engraftment reduced the number of Αß plaques and produced an increase in M2 microglia polarization in the hippocampus of APP/PS1 mice, suggesting an anti-inflammatory effect of stem cell transplantation. NSC also reversed the hyperlocomotor activity and increased the number of microglia in the hippocampus of APP/PS1 mice. No impairment of short or long-term memory was observed in APP/PS1 mice. Overall, this study highlights the potential beneficial effects of transplanting NSC or MSC for AD treatment.

Current Status and Challenges of Stem Cell Treatment for Alzheimer's Disease.

Neurodegenerative diseases called tauopathies, such as Alzheimer's disease (AD), frontotemporal dementia, progressive supranuclear palsy, and Parkinson's disease, among others, are characterized by the pathological processing and accumulation of tau protein. AD is the most prevalent neurodegenerative disease and is characterized by two lesions: neurofibrillary tangles (NFTs) and neuritic plaques. The presence of NFTs in the hippocampus and neocortex in early and advanced stages, respectively, correlates with the patient's cognitive deterioration. So far, no drugs can prevent, decrease, or limit neuronal death due to abnormal pathological tau accumulation. Among potential non-pharmacological treatments, physical exercise has been shown to stimulate the development of stem cells (SCs) and may be useful in early stages. However, this does not prevent neuronal death from the massive accumulation of NFTs. In recent years, SCs therapies have emerged as a promising tool to repopulate areas involved in cognition in neurodegenerative diseases. Unfortunately, protocols for SCs therapy are still being developed and the mechanism of action of such therapy remains unclear. In this review, we show the advances and limitations of SCs therapy. Finally, we provide a critical analysis of its clinical use for AD.

GABA Neurotransmission of the Suprachiasmatic Nucleus Is Modified During Rat Postnatal Development.

The suprachiasmatic nucleus (SCN) of the hypothalamus is the brain structure that controls circadian rhythms in mammals. The SCN is formed by two neuroanatomical regions: the ventral and dorsal. Gamma-aminobutyric acid (GABA) neurotransmission is important for the regulation of circadian rhythms. Excitatory GABA effects have been described in both SCN regions displaying a circadian variation. Moreover, the GABAergic system transfers photic information from the ventral to the dorsal SCN. However, there is almost no knowledge about GABA neurotransmission during the prenatal or postnatal development of the SCN. Here, we used whole-cell patch-clamp recordings to study spontaneous inhibitory postsynaptic currents (IPSCs) in the two SCN regions, at two zeitgeber times (day or night), and at four postnatal (P) ages: P3-5, P7-9, P12-15, and P20-25. The results herein show that the three analyzed parameters of the IPSCs, frequency, amplitude, and decay time, were significantly affected by the postnatal age: mostly, the IPSC frequency increased with age, principally in the ventral SCN in both day and night recordings; similarly, the amplitude of IPSCs augmented with age, especially at night, whereas the IPSC decay time was reduced (it was faster) with postnatal age, mainly during the day. Our findings first reveal that parameters of GABA neurotransmission are modified by postnatal development, implying that synaptic adjustments are required for an appropriate maturation of the GABAergic system in the SCN.

Mechanisms of vertebrate neural plate internalization.

The internalization of multi-cellular tissues is a key morphogenetic process during animal development and organ formation. A good example of this is the initial stages of vertebrate central nervous system formation whereby a transient embryonic structure called the neural plate is able to undergo collective cell rearrangements within the dorsal midline. Despite the fact that defects in neural plate midline internalization may result in a series of severe clinical conditions, such as spina bifida and anencephaly, the biochemical and biomechanical details of this process remain only partially characterized. Here we review the main cellular and molecular mechanisms underlying midline cell and tissue internalization during vertebrate neural tube formation. We discuss the contribution of collective cell mechanisms including convergence and extension, as well as apical constriction facilitating midline neural plate shaping. Furthermore, we summarize recent studies that shed light on how the interplay of signaling pathways and cell biomechanics modulate neural plate internalization. In addition, we discuss how adhesion-dependent cell-cell contact appears to be a critical component during midline cell convergence and surface cell contraction via cell-cell mechanical coupling. We envision that more detailed high-resolution quantitative data at both cell and tissue levels will be required to properly model the mechanisms of vertebrate neural plate internalization with the hope of preventing human neural tube defects.

Nevus azul celular con satelitosis y velo azul blanquecino simulando un melanoma, a propósito de un caso / Cellular blue nevus with satellitosis and blue veil whitish simulating a melanoma, purpose of a case

Los nevi azules son proliferaciones melanocíticas dendríticas benignas a nivel dérmico, congénitos o adquiridos, debido a un defecto migratorio embrionario de melanocitos a partir de la cresta neural. Se manifiestan clásicamente como una pápula, nódulo o placa de color azul o azul-gris. Muchos subtipos histológicos se han descrito, siendo los más comunes el nevus azul común, nevus azul celular y nevus azul combinado. Las formas esporádicas incluyen al nevus azul lineal, eruptivo, agminado y con satelitosis. La dermatoscopía característica muestra un patrón de pigmentación homogéneo monocromático azul o azul-grisáceo, con ausencia de otras estructuras. Sin embargo, se han descrito también patrones de pigmentación dicromáticos y multicromáticos, además de estructuras tales como red de pigmento, puntos, glóbulos, proyecciones radiadas, pseudópodos, áreas cicatriciales blanquecinas, patrón vascular y rosetas. El diagnóstico diferencial de los nevi azules incluye lesiones melanocíticas y no melanocíticas, benignas y malignas, destacando entre ellas el melanoma. Se presenta el caso de un paciente de sexo masculino de 30 años, portador de un nevus azul celular con cambios de rápida evolución, con desarrollo de lesiones satélites y un aspecto dermatoscópico sugerente de malignidad, simulando un melanoma.

Blue nevi are benign, congenital, or acquired, dermal dendritic melanocytic proliferations due to an embryonic migratory defect of melanocytes starting from the neural crest. They classically manifest as a blue or blue-gray papule, nodule, or plaque. Many histological subtypes have been described, including common blue nevus, cellular blue nevus and combined blue nevus. Sporadic forms include linear blue nevus, eruptive, agminate and with satellitosis. Characteristic dermoscopy shows a homogeneous monochromatic blue or steel-blue pigmentation pattern, with the absence of other structures. However, dichromatic and multichromatic pigmentation patterns have also been described, in addition to structures such as pigment network, dots, globules, streaks, pseudopods, whitish scar areas, vascular pattern and rosettes. Differential diagnosis of blue nevi includes melanocytic and non-melanocytic, benign and malignant lesions, most notably melanoma. The case of a 30-year-old male patient is presented, with a cellular blue nevus with rapidly evolving changes, with development of satellite lesions and a dermoscopic appearance suggestive of malignancy, mimicking melanoma.

Lesões neurais da cavidade oral: estudo clinicopatológico de 171 casos / Neural lesions of the oral cavity: study clinicopathological of 171 cases

Lesões neurais são incomuns na região de cabeça e pescoço, especialmente na cavidade oral, representa n d o o principal grupo de lesões da cavidade oral com células fusiformes. O diagnóstico destas lesões pode ser desafiador já que podem compartilhar características clínicas e microscópicas similares , podendo ter natureza reacional ou neoplásica. O objetivo deste trabalho foi avaliar as características clínicas e microscópicas das lesões neurais diagnosticadas no Laboratório de Patologia Oral da Faculdade de Odontologia da Universidade Federal do R io d e Janeiro Brasil no período entre 1971 até 20 2 1 Os casos foram obtido s após a revisão dos arquivos da instituição e o diagnóstico final de cada caso foi confirmado pela análise microscópica . A s características clínicas e microscópicas de cada caso foram apresentadas de maneira descritiva. Cento e setenta e um a lesões neurais foram identificadas . As lesões apresentaram se principalmente como nódulos normocrômicos, assintomáticos, de consistência firme e superfície lisa, localizados na língua de mulheres com m é dia de idade de 43, 5 anos Os di agnósticos mais comuns foram hamartoma neurovascular 30,4 tumor de cé lulas granulares (1 7 %), neuroma traumático ( 1 6,4 %)%), seguidos de placa neurogênica subgemal (1 2,9 %), neuroma solitário circunscrito ( 9,9 %)%), schwannoma 7,6 e neurofibroma 5, 8 O presente e stud o provavelmente representa uma das maior es casuística s de lesões neurais da cavidade oral disponível na literatura. (AU)

Neural lesions ar e uncommon in the head and neck region, parti cularly in the oral cavity, representing the most common group of oral spindle cell lesions of the oral cavity. The diagnosis of neural lesions may be ch a llenging since it may share cli nical and micros copical fe atures, showing reactive or neoplastic nature. The aim of the present study was to evaluate the clinical and microscopical features of neural lesions diagnosed in the Oral P athology Labora tory of th e School of Dentistry of Federa l U niversity of Rio d e Jan eiro Brazil in a period between 1971 and 20 21 . The cases were obtained from the review of the files of this institution and the final diagnosis were confirmed after microsc opical evaluati on O ne hu n dred and seventy one neural lesions were identified . The lesions presented preferably as asymptomatic and normochromic nodules of tender consistency and smooth surface, located in the tongue of women with median age of 4 3, 5 year s The most com mo n diagnose s were neurovascular hamartoma 30,4 granular cell tumor (1 7 %)%), traumatic neuroma 1 6,4 and followed by subgemmal neurogenous plaque 1 2,9 %), circumscribed solitary neuroma 9,9 %)%), schwannoma ( 7,6 and neurofibroma ( 5, 8 %)%). The present study likely re p resent s one of the largest series of neural lesions of the oral cavity of the literature. (AU)

Changes in neuronal excitability and synaptic transmission in nucleus accumbens in a transgenic Alzheimer's disease mouse model.

Several previous studies showed that hippocampus and cortex are affected in Alzheimer's disease (AD). However, other brain regions have also been found to be affected and could contribute with new critical information to the pathophysiological basis of AD. For example, volumetric studies in humans have shown a significant atrophy of the striatum, particularly in the nucleus Accumbens (nAc). The nAc is a key component of the limbic reward system and it is involved in cognition and emotional behaviors such as pleasure, fear, aggression and motivations, all of which are affected in neurodegenerative diseases such as AD. However, its role in AD has not been extensively studied. Therefore, using an AD mouse model, we investigated if the nAc was affected in 6 months old transgenic 2xTg (APP/PS1) mice. Immunohistochemistry (IHC) analysis in 2xTg mice showed increased intraneuronal Aß accumulation, as well as occasional extracellular amyloid deposits detected through Thioflavin-S staining. Interestingly, the intracellular Aß pathology was associated to an increase in membrane excitability in dissociated medium spiny neurons (MSNs) of the nAc. IHC and western blot analyses showed a decrease in glycine receptors (GlyR) together with a reduction in the pre- and post-synaptic markers SV2 and gephyrin, respectively, which correlated with a decrease in glycinergic miniature synaptic currents in nAc brain slices. Additionally, voltage-clamp recordings in dissociated MSNs showed a decrease in AMPA- and Gly-evoked currents. Overall, these results showed intracellular Aß accumulation together with an increase in excitability and synaptic alterations in this mouse model. These findings provide new information that might help to explain changes in motivation, anhedonia, and learning in the onset of AD pathogenesis.

Surface contraction waves or cell proliferation waves in the presumptive neurectoderm during amphibian gastrulation: Mexican axolotl versus African clawed frog.

This essay represents a critical analysis of the literary data on various types of waves occurring in the amphibian embryos during gastrulation. A surface contraction wave travels through the presumptive neurectoderm during Mexican axolotl gastrulation. This wave coincides temporally and spatially with involution of the inducing chordomesoderm and with the prospective neural plate. By contrast, there is no similar surface contraction wave during African clawed frog gastrulation. However, the clawed frog displays the waves of DNA synthesis and mitosis in the presumptive neurectoderm during gastrulation, whereas no such waves were discovered in axolotl gastrulae. These sets of experimental data are in accordance with the contemporary concept of considerable ontogenetic diversity of the class Amphibia.

A specialized reciprocal connectivity suggests a link between the mechanisms by which the superior colliculus and parabigeminal nucleus produce defensive behaviors in rodents.

The parabigeminal nucleus (PBG) is the mammalian homologue to the isthmic complex of other vertebrates. Optogenetic stimulation of the PBG induces freezing and escape in mice, a result thought to be caused by a PBG projection to the central nucleus of the amygdala. However, the isthmic complex, including the PBG, has been classically considered satellite nuclei of the Superior Colliculus (SC), which upon stimulation of its medial part also triggers fear and avoidance reactions. As the PBG-SC connectivity is not well characterized, we investigated whether the topology of the PBG projection to the SC could be related to the behavioral consequences of PBG stimulation. To that end, we performed immunohistochemistry, in situ hybridization and neural tracer injections in the SC and PBG in a diurnal rodent, the Octodon degus. We found that all PBG neurons expressed both glutamatergic and cholinergic markers and were distributed in clearly defined anterior (aPBG) and posterior (pPBG) subdivisions. The pPBG is connected reciprocally and topographically to the ipsilateral SC, whereas the aPBG receives afferent axons from the ipsilateral SC and projected exclusively to the contralateral SC. This contralateral projection forms a dense field of terminals that is restricted to the medial SC, in correspondence with the SC representation of the aerial binocular field which, we also found, in O. degus prompted escape reactions upon looming stimulation. Therefore, this specialized topography allows binocular interactions in the SC region controlling responses to aerial predators, suggesting a link between the mechanisms by which the SC and PBG produce defensive behaviors.

Reimplante de falange distal de dedo sin anastomosis venosa con anestesia local / Distal phalanx replantation under local anesthesia and without venous anastomosis

Presentamos a un paciente que sufrió una amputación traumática de la falange distal del 5to dedo de su mano izquierda, y fue tratado mediante un reimplante sin anastomosis venosa. En el mismo acto quirúrgico, se le realizó una artrodesis definitiva con clavijas. La cirugía se efectuó con anestesia troncular del dedo, por lo cual no se requirió de un anestesista ni fue necesario un tiempo adecuado de ayuno. Debido a la localización distal de la amputación y a la ausencia de una vena dorsal viable para ser anastomosada, se optó por un drenaje venoso controlado mediante la extracción de la placa ungueal, el frotado del lecho ungueal y la colocación periódica (cada 3 h, por 7 días) de una gasa impregnada con heparina. Además, el paciente fue anticoagulado con enoxaparina 40 mg y ácido acetilsalicílico cada 24 h, por 21 días. El reimplante fue exitoso. Nivel de Evidencia: IV

We present a patient who experienced a traumatic amputation of his left fifth finger distal phalanx, and was treated using replantation without venous anastomosis. The same surgical procedure also included a final arthrodesis with Kirschner wires. Surgery was performed with digital block anesthesia, which did not require the presence of an anesthesiologist nor fasting. The distal level of the amputation and the lack of viable options for dorsal vein anastomosis motivated our decision for venous drainage controlled by nail-plate removal, nail-bed scrubbing and periodic (every 3 hours during 7 days) dressing with heparin-impregnated gauze. In addition, the patient received anticoagulant therapy with aspirin and enoxaparin 40 mg every 24 hours for 21 days. The replantation procedure was a success. Level of Evidence: IV