Myoclonus improvement after seizures in progressive myoclonic epilepsy type 7: a case report.

BACKGROUND: Progressive Myoclonic Epilepsy (PME) is a group of rare diseases that are difficult to differentiate from one another based on phenotypical characteristics. CASE REPORT: We report a case of PME type 7 due to a pathogenic variant in KCNC1 with myoclonus improvement after epileptic seizures. DISCUSSION: Myoclonus improvement after seizures may be a clue to the diagnosis of Progressive Myoclonic Epilepsy type 7.

Apraxia of Eyelid Opening and Blepharospasm in Two Spinocerebellar Ataxia Type 3 Patients.

BACKGROUND: Neuroophthalmological phenotypical particularities of SCA3. PHENOMENOLOGY: Eyelid opening apraxia and asymmetrical blepharospasm. EDUCATIONAL VALUE: To illustrate the phenomenology for purposes of education.

Adenosine kinase deficiency presenting with tortuous cervical arteries: A risk factor for recurrent stroke.

Adenosine kinase (ADK) deficiency is a very rare inborn error of methionine and adenosine metabolism. It is characterized by developmental delay, hypotonia, epilepsy, facial dysmorphism, failure to thrive, transient liver dysfunction with cholestasis, recurrent hypoglycemia, and cardiac defects. Only 26 cases (16 families) of ADK deficiency have been published since its identification in 2011. Vascular abnormalities in cervical arteries and cerebral stroke have never been reported in this condition. Here, we describe two patients with ADK deficiency and vascular tortuosity leading to stroke in one of them. ADK deficiency is a rare inborn error of methionine metabolism with a complex phenotype that might be associated with cerebrovascular abnormalities and stroke.

Genomic damage in Mugil curema (Actinopterygii: Mugilidae) reveals the effects of intense urbanization on estuaries in northeastern Brazil.

The largest metropolitan centers in northeastern region of Brazil are all located near the coast, and industrial, tourist, and agro-industrial activities are the principal causes of water contamination due to discharges of untreated sewage. Adverse environmental conditions can often be detected by analyzing the genetic material of organisms exposed to pollutants, and furnish an overview of environmental quality. We evaluated possible damage to the DNA of one of the fish resources most widely consumed and commercialized by coastal communities in northeastern Brazil, Mugil curema ("tainha"). Erythrocytes from M. curema were analyzed by the presence of micronuclei and by comet assay (single cell gel electrophoresis, SCGE). Statistical comparisons to both tests revealed considerably greater genomic damage in polluted estuaries than in the control site (p < 0.05), suggesting strong genotoxic impacts on the specimens evaluated, principally among those taken near localities with dense demographic and industrial development.

A habitable fluvio-lacustrine environment at Yellowknife Bay, Gale crater, Mars.

The Curiosity rover discovered fine-grained sedimentary rocks, which are inferred to represent an ancient lake and preserve evidence of an environment that would have been suited to support a martian biosphere founded on chemolithoautotrophy. This aqueous environment was characterized by neutral pH, low salinity, and variable redox states of both iron and sulfur species. Carbon, hydrogen, oxygen, sulfur, nitrogen, and phosphorus were measured directly as key biogenic elements; by inference, phosphorus is assumed to have been available. The environment probably had a minimum duration of hundreds to tens of thousands of years. These results highlight the biological viability of fluvial-lacustrine environments in the post-Noachian history of Mars.

Elemental geochemistry of sedimentary rocks at Yellowknife Bay, Gale crater, Mars.

Sedimentary rocks examined by the Curiosity rover at Yellowknife Bay, Mars, were derived from sources that evolved from an approximately average martian crustal composition to one influenced by alkaline basalts. No evidence of chemical weathering is preserved, indicating arid, possibly cold, paleoclimates and rapid erosion and deposition. The absence of predicted geochemical variations indicates that magnetite and phyllosilicates formed by diagenesis under low-temperature, circumneutral pH, rock-dominated aqueous conditions. Analyses of diagenetic features (including concretions, raised ridges, and fractures) at high spatial resolution indicate that they are composed of iron- and halogen-rich components, magnesium-iron-chlorine-rich components, and hydrated calcium sulfates, respectively. Composition of a cross-cutting dike-like feature is consistent with sedimentary intrusion. The geochemistry of these sedimentary rocks provides further evidence for diverse depositional and diagenetic sedimentary environments during the early history of Mars.

Martian fluvial conglomerates at Gale crater.

Observations by the Mars Science Laboratory Mast Camera (Mastcam) in Gale crater reveal isolated outcrops of cemented pebbles (2 to 40 millimeters in diameter) and sand grains with textures typical of fluvial sedimentary conglomerates. Rounded pebbles in the conglomerates indicate substantial fluvial abrasion. ChemCam emission spectra at one outcrop show a predominantly feldspathic composition, consistent with minimal aqueous alteration of sediments. Sediment was mobilized in ancient water flows that likely exceeded the threshold conditions (depth 0.03 to 0.9 meter, average velocity 0.20 to 0.75 meter per second) required to transport the pebbles. Climate conditions at the time sediment was transported must have differed substantially from the cold, hyper-arid modern environment to permit aqueous flows across several kilometers.

L1cam acts as a modifier gene for members of the endothelin signalling pathway during enteric nervous system development.

BACKGROUND: The enteric nervous system originates from neural crest cells that migrate into the embryonic foregut and then sequentially colonize the midgut and hindgut. Defects in neural crest migration result in regions of the gut that lack enteric ganglia, a condition in humans called Hirschsprung's disease. The high degree of phenotypic variability reported in Hirschsprung's disease suggests the involvement of modifier genes. METHODS: We used a two-locus complementation approach to screen for genetic interactions between L1cam and members of the endothelin signalling pathway. Immunohistochemistry was used to label PGP9.5(+) enteric neurons and Sox10(+) neural crest-derived cells in wholemount preparations of embryonic gut. Key Results Loss or haploinsufficiency of L1cam significantly increased the severity of aganglionosis in Et-3 and Ednrb null mutant embryos. Furthermore, the colonization of the developing gut by neural crest-derived cells was significantly delayed in L1cam(-/y) ; Et-3(-/-) and L1cam(-/y) ;Ednrb(sl/sl) embryos. CONCLUSIONS & INFERENCES: We have identified the X-linked gene, L1cam, as the first modifier gene for members of the endothelin signalling pathway during development of the enteric nervous system. Mutations in L1CAM may act to modulate the severity of aganglionosis in some cases of Hirschsprung's disease.

The role of neural activity in the migration and differentiation of enteric neuron precursors.

BACKGROUND: As they migrate through the developing gut, a sub-population of enteric neural crest-derived cells (ENCCs) begins to differentiate into neurons. The early appearance of neurons raises the possibility that electrical activity and neurotransmitter release could influence the migration or differentiation of ENNCs. METHODS: The appearance of neuronal sub-types in the gut of embryonic mice was examined using immunohistochemistry. The effects of blocking various forms of neural activity on ENCC migration and neuronal differentiation were examined using explants of cultured embryonic gut. KEY RESULTS: Nerve fibers were present in close apposition to many ENCCs. Commencing at E11.5, neuronal nitric oxide synthase (nNOS), calbindin and IK(Ca) channel immunoreactivities were shown by sub-populations of enteric neurons. In cultured explants of embryonic gut, tetrodotoxin (TTX, an inhibitor of action potential generation), nitro-L-arginine (NOLA, an inhibitor of nitric oxide synthesis) and clotrimazole (an IK(Ca) channel blocker) did not affect the rate of ENCC migration, but tetanus toxin (an inhibitor of SNARE-mediated vesicle fusion) significantly impaired ENCC migration as previously reported. In explants of E11.5 and E12.5 hindgut grown in the presence of TTX or tetanus toxin there was a decrease in the number nNOS+ neurons close to the migratory wavefront, but no significant difference in the proportion of all ENCC that expressed the pan-neuronal marker, Hu. CONCLUSIONS & INFERENCES: (i) Some enteric neuron sub-types are present very early during the development of the enteric nervous system. (ii) The rate of differentiation of some sub-types of enteric neurons appears to be influenced by TTX- and tetanus toxin-sensitive mechanisms.

Effects of tissue age, presence of neurones and endothelin-3 on the ability of enteric neurone precursors to colonize recipient gut: implications for cell-based therapies.

BACKGROUND Most enteric neurones arise from neural crest cells that originate in the post-otic hindbrain, and migrate into and along the developing gastrointestinal tract. There is currently great interest in the possibility of cell therapy to replace diseased or absent enteric neurones in patients with enteric neuropathies, such as Hirschsprung's disease. However, it is unclear whether neural crest stem/progenitor cells will be able to colonize colon (i) in which the mesenchyme has differentiated into distinct layers, (ii) that already contains enteric neurones or (iii) that lacks a gene expressed by the gut mesenchyme, such as endothelin-3 (Et-3). METHODS Co-cultures were used to examine the ability of enteric neural crest-derived cells (ENCCs) from E11.5 mouse gut to colonize a variety of recipient hindguts. KEY RESULTS Enteric neural crest-derived cells migrated and gave rise to neurones in E14.5 and E16.5 aneural colon in which the external muscle layers had differentiated, but they did not migrate as far as in younger colon. There was no evidence of altered ENCC proliferation, cell death or neuronal differentiation in older recipient explants. Enteric neural crest-derived cells failed to enter most recipient E14.5 and E16.5 colon explants already containing enteric neurones, and the few that did showed very limited migration. Finally, ENCCs migrated a shorter distance and a higher proportion expressed the pan-neuronal marker, Hu, in recipient E11.5 Et-3(-/-) colon compared to wild-type recipient colon. CONCLUSIONS & INFERENCES Age and an absence of Et-3 from the recipient gut both significantly reduced but did not prevent ENCC migration, but the presence of neurones almost totally prevented ENCC migration.

The migratory behavior of immature enteric neurons.

While they are migrating caudally along the developing gut, around 10%-20% of enteric neural crest-derived cells start to express pan-neuronal markers and tyrosine hydroxylase (TH). We used explants of gut from embryonic TH-green fluorescence protein (GFP) mice and time-lapse microscopy to examine whether these immature enteric neurons migrate and their mode of migration. In the gut of E10.5 and E11.5 TH-GFP mice, around 50% of immature enteric neurons (GFP(+) cells) migrated, with an average speed of around 15 mum/h. This is slower than the speed at which the population of enteric neural crest-derived cells advances along the developing gut, and hence neuronal differentiation seems to slow, but not necessarily halt, the caudal migration of enteric neural crest cells. Most migrating immature enteric neurons migrated caudally by extending a long-leading process followed by translocation of the cell body. This mode of migration is different from that of non-neuronal enteric neural crest-derived cells and neural crest cells in other locations, but resembles that of migrating neurons in many regions of the developing central nervous system (CNS). In migrating immature enteric neurons, a swelling often preceded the movement of the nucleus in the direction of the leading process. However, the centrosomal marker, pericentrin, was not localized to either the leading process or swelling. This seems to be the first detailed report of neuronal migration in the developing mammalian peripheral nervous system.

Effects of different regions of the developing gut on the migration of enteric neural crest-derived cells: a role for Sema3A, but not Sema3F.

The enteric nervous system arises from vagal (caudal hindbrain) and sacral level neural crest-derived cells that migrate into and along the developing gut. Data from previous studies have suggested that (i) there may be gradients along the gut that induce the caudally directed migration of vagal enteric neural precursors (ENPs), (ii) exposure to the caecum might alter the migratory ability of vagal ENPs and (iii) Sema3A might regulate the entry into the hindgut of ENPs derived from sacral neural crest. Using co-cultures we show that there is no detectable gradient of chemoattractive molecules along the pre-caecal gut that specifically promotes the caudally directed migration of vagal ENPs, although vagal ENPs migrate faster caudally than rostrally along explants of hindgut. Exposure to the caecum did not alter the rate at which ENPs colonized explants of hindgut, but it did alter the ability of ENPs to colonize the midgut. The co-cultures also revealed that there is localized expression of a repulsive cue in the distal hindgut, which might delay the entry of sacral ENPs. We show that Sema3A is expressed by the hindgut mesenchyme and its receptor, neuropilin-1, is expressed by migrating ENPs. Furthermore, there is premature entry of sacral ENPs and extrinsic axons into the distal hindgut of fetal mice lacking Sema3A. These data show that Sema3A expressed by the distal hindgut regulates the entry of sacral ENPs and extrinsic axons into the hindgut. ENPs did not express neuropilin-2 and there was no detectable change in the timetable by which ENPs colonize the gut in mice lacking neuropilin-2.

Concussion history is not a predictor of computerised neurocognitive performance.

BACKGROUND: The long term effects of self reported concussion on neurocognitive functioning have been found to be variable. OBJECTIVES: To evaluate cognitive performance on the Headminder concussion resolution index (CRI) and ImPACT assessment tests of subjects with and without a history of self reported concussion. METHODS: A retrospective analysis was completed on 235 Headminder CRI baseline assessments and 264 ImPACT baseline assessments. Participants were divided into four groups on the basis of reported number of concussions (zero, one, two, or three). Multivariate analysis of variance was used to evaluate differences between the concussion history groups on the two computer based concussion assessment programs. RESULTS: Multivariate analysis of variance indicated no significant difference between those with and without a history of concussion on the CRI (Lambda = 0.963, F((15, 627.05)) = 0.57, p = 0.898). It also revealed no significant differences between groups on the ImPACT test (Lambda = 0.951, F((12, 672.31)) = 1.07, p = 0.381). CONCLUSIONS: The results suggest that either long term cognitive decrements may not be associated with a history of concussion or the decrements may be subtle and undetectable by these computer programs.

Phenotypes of neural-crest-derived cells in vagal and sacral pathways.

Enteric neurons arise from vagal and sacral level neural crest cells. To examine the phenotype of neural-crest-derived cells in vagal and sacral pathways, we used antisera to Sox10, p75, Phox2b, and Hu, and transgenic mice in which the expression of green fluorescent protein was under the control of the Ret promoter. Sox10 was expressed prior to the emigration of vagal cells, whereas p75 was expressed shortly after their emigration. Most crest-derived cells that emigrated adjacent to somites 1-4 migrated along a pathway that was later followed by the vagus nerve. A sub-population of these vagal cells coalesced to form vagal ganglia, whereas others continued their migration towards the heart and gut. Cells that coalesced into vagal ganglia showed a different phenotype from cells in the migratory streams proximal and distal to the ganglia. Only a sub-population of the vagal cells that first entered the foregut expressed Phox2b or Ret. Sacral neural crest cells gave rise to pelvic ganglia and some neurons in the hindgut. The pathways of sacral neural crest cells were examined by using DbetaH-nlacZ mice. Sacral cells appeared to enter the distal hindgut around embryonic day 14.5. Very few of the previously demonstrated, but rare, neurons that were present in the large intestine of Ret null mutants and that presumably arose from the sacral neural crest expressed nitric oxide synthase, unlike their counterparts in Ret heterozygous mice.

The canine right caudal and accessory lobe pulmonary veins: revised anatomical description, clinical relevance, and embryological implications.

Necropsy dissections were performed on nine dogs to provide an anatomical description of the right caudal and accessory lobe pulmonary veins. In all dogs, the pulmonary vein from the right caudal lung lobe initially paralleled the right caudal lung lobe bronchus, running cranially, medially, and ventrally. It diverged from the bronchus at the level of the pulmonary artery and bronchus of the accessory lung lobe. At this point, the pulmonary vein from the right caudal lung lobe coursed dorsal to the pulmonary artery and bronchus of the accessory lung lobe. Medial to the bronchus of the accessory lung lobe, it received the pulmonary vein from the accessory lung lobe on its ventral surface. Within the pericardium, this common venous trunk merged with the caudal aspect of the left atrium either with or immediately adjacent to the left caudal lobe pulmonary vein. These findings were corroborated during surgical dissection to achieve isolation of the heart in five dogs as part of an experimental study on intravascular gene delivery to the heart. These anatomical findings are relevant to clinical and experimental surgery and raise interesting questions about the embryological development of pulmonary veins in the dog.

Adaptação da escala de homofobia implícita e explícita ao contexto brasileiro / Adaptation of the implicit and explicit homophobia scale to the brazilian context

O grande número de atitudes agressivas e comportamentos discriminatórios reportados com relação aos homossexuais tem sido amplamente discutido. Estudos recentes têm mostrado que o preconceito se modificou, tornando-se mais sutil. No entanto, são escassos os estudos que procuram enfatizar essa modificação no que diz respeito ao preconceito frente a estes grupos minoritários. Assim, o objetivo deste estudo foi adaptar a escala de homofobia implícita e explícita para o contexto brasileiro. Participaram desta pesquisa 231 estudantes universitários, com idade variando de 17 a 55 anos (M = 24,0; DP= 5,38), sendo a maioria (51,5 porcento) do sexo masculino. Estes responderam à escala mencionada e questões sócio-demográficas. Os resultados da análise fatorial confirmatória corroboraram a estrutura bi-fatorial da medida. Conjuntamente, o instrumento apresentou consistência interna (alfa de Cronbach = 0,87), mostrando-se uma medida fidedigna para utilização neste contexto (AU)

Adaptação da escala de homofobia implícita e explícita ao contexto brasileiro / Adaptation of the implicit and explicit homophobia scale to the brazilian context

O grande número de atitudes agressivas e comportamentos discriminatórios reportados com relação aos homossexuais tem sido amplamente discutido. Estudos recentes têm mostrado que o preconceito se modificou, tornando-se mais sutil. No entanto, são escassos os estudos que procuram enfatizar essa modificação no que diz respeito ao preconceito frente a estes grupos minoritários. Assim, o objetivo deste estudo foi adaptar a escala de homofobia implícita e explícita para o contexto brasileiro. Participaram desta pesquisa 231 estudantes universitários, com idade variando de 17 a 55 anos (M = 24,0; DP= 5,38), sendo a maioria (51,5 porcento) do sexo masculino. Estes responderam à escala mencionada e questões sócio-demográficas. Os resultados da análise fatorial confirmatória corroboraram a estrutura bi-fatorial da medida. Conjuntamente, o instrumento apresentou consistência interna (alfa de Cronbach = 0,87), mostrando-se uma medida fidedigna para utilização neste contexto