Variante rara de RNF213 en adolescente con enfermedad de moyamoya / Rare RNF213 variant in adolescent with moyamoya disease

Introducción: La enfermedad de moyamoya es una enfermedad estenooclusiva progresiva de las principales arterias intracraneales. Los individuos afectados corren el riesgo de sufrir un accidente cerebrovascular hemorrágico o isquémico intracraneal, deterioro cognitivo y retrasos en el desarrollo. Se han identificado varios genes de susceptibilidad. La variante p.R4810K en el gen RNF213 se ha identificado en el 95% de los pacientes con enfermedad de moyamoya familiar. Caso clínico: Presentamos el caso de una adolescente de 15 años que se presentó con quejas principales de disgrafía y falta de coordinación en la mano derecha con dos meses de evolución. La resonancia magnética cerebral reveló varias lesiones isquémicas con diferentes ritmos de evolución y la angiorresonancia magnética mostró múltiples estenosis suboclusivas. En el estudio de las secuencias de las regiones codificantes y de las regiones intrónicas flanqueantes (±8 pb) del gen RNF213, se detectó la variante c.12185G>A, p.(Arg4062Gln) en heterocigosidad en el gen RNF213. Este resultado indica que la paciente es heterocigota para la variante c.12185G>A, p.(Arg4062Gln) en el gen RNF213. La variante detectada ya ha sido descrita en la bibliografía como una variante fundadora en la población asiática, asociada a síndrome de moyamoya. Esta variante está descrita en ClinVar como una variante de significado clínico desconocido. Además, no está descrita en las bases de datos poblacionales (dbSNP, ESP y gnomAD). Conclusión: Hasta donde sabemos, la variante p.(Arg4062Gln) se ha notificado en tres pacientes japoneses con enfermedad de moyamoya y en uno europeo. Por lo tanto, nuestro paciente fue el segundo europeo con enfermedad de moyamoya con esta variante identificada.(AU)

Introduction: Moyamoya disease is a progressive steno-occlusive disease of the major intracranial arteries. Affected individuals are at risk for intracranial hemorrhagic or ischemic stroke, cognitive impairment, and developmental delays. Several susceptibility genes have been identified. The p.R4810K variant in the RNF213 gene has been identified in 95% of patients with familial moyamoya disease. Case report: We present the case of a 15-year-old adolescent girl who presented with chief complaints of dysgraphia, lack of coordination in the right hand, with two months of evolution. Cerebral magnetic resonance imaging revealed several ischemic lesions with different rates of evolution and magnetic resonance angiography showed multiple subocclusive stenoses. In the study of the sequences of the coding regions and intronic flanking regions (±8 bp) of the RNF213 gene, the variant c.12185G>A, p.(Arg4062Gln) was detected in heterozygosity in the RNF213 gene. This result indicates that the patient is heterozygous for the c.12185G>A, p.(Arg4062Gln) variant in the RNF213 gene. The detected variant has already been reported in the literature as a founder variant in the Asian population, associated with moyamoya syndrome. This variant is described in ClinVar as a variant of unknown clinical significance? Furthermore, it is not described in population databases (dbSNP, ESP, gnomAD). Conclusion: To our knowledge, the p.(Arg406262Gln) variant has been reported in three Japanese moyamoya disease patients and one European. Therefore, our patient was the second European moyamoya disease patient with this variant identified.(AU)

Rare RNF213 variant in adolescent with moyamoya disease. / Variante rara de RNF213 en adolescente con enfermedad de moyamoya.

INTRODUCTION: Moyamoya disease is a progressive steno-occlusive disease of the major intracranial arteries. Affected individuals are at risk for intracranial hemorrhagic or ischemic stroke, cognitive impairment, and developmental delays. Several susceptibility genes have been identified. The p.R4810K variant in the RNF213 gene has been identified in 95% of patients with familial moyamoya disease. CASE REPORT: We present the case of a 15-year-old adolescent girl who presented with chief complaints of dysgraphia, lack of coordination in the right hand, with two months of evolution. Cerebral magnetic resonance imaging revealed several ischemic lesions with different rates of evolution and magnetic resonance angiography showed multiple subocclusive stenoses. In the study of the sequences of the coding regions and intronic flanking regions (±8 bp) of the RNF213 gene, the variant c.12185G>A, p.(Arg4062Gln) was detected in heterozygosity in the RNF213 gene. This result indicates that the patient is heterozygous for the c.12185G>A, p.(Arg4062Gln) variant in the RNF213 gene. The detected variant has already been reported in the literature as a founder variant in the Asian population, associated with moyamoya syndrome. This variant is described in ClinVar as a variant of unknown clinical significance? Furthermore, it is not described in population databases (dbSNP, ESP, gnomAD). CONCLUSION: To our knowledge, the p.(Arg406262Gln) variant has been reported in three Japanese moyamoya disease patients and one European. Therefore, our patient was the second European moyamoya disease patient with this variant identified.

TITLE: Variante rara de RNF213 en adolescente con enfermedad de moyamoya.Introducción. La enfermedad de moyamoya es una enfermedad estenooclusiva progresiva de las principales arterias intracraneales. Los individuos afectados corren el riesgo de sufrir un accidente cerebrovascular hemorrágico o isquémico intracraneal, deterioro cognitivo y retrasos en el desarrollo. Se han identificado varios genes de susceptibilidad. La variante p.R4810K en el gen RNF213 se ha identificado en el 95% de los pacientes con enfermedad de moyamoya familiar. Caso clínico. Presentamos el caso de una adolescente de 15 años que se presentó con quejas principales de disgrafía y falta de coordinación en la mano derecha con dos meses de evolución. La resonancia magnética cerebral reveló varias lesiones isquémicas con diferentes ritmos de evolución y la angiorresonancia magnética mostró múltiples estenosis suboclusivas. En el estudio de las secuencias de las regiones codificantes y de las regiones intrónicas flanqueantes (±8 pb) del gen RNF213, se detectó la variante c.12185G>A, p.(Arg4062Gln) en heterocigosidad en el gen RNF213. Este resultado indica que la paciente es heterocigota para la variante c.12185G>A, p.(Arg4062Gln) en el gen RNF213. La variante detectada ya ha sido descrita en la bibliografía como una variante fundadora en la población asiática, asociada a síndrome de moyamoya. Esta variante está descrita en ClinVar como una variante de significado clínico desconocido. Además, no está descrita en las bases de datos poblacionales (dbSNP, ESP y gnomAD). Conclusión. Hasta donde sabemos, la variante p.(Arg4062Gln) se ha notificado en tres pacientes japoneses con enfermedad de moyamoya y en uno europeo. Por lo tanto, nuestro paciente fue el segundo europeo con enfermedad de moyamoya con esta variante identificada.

Clinical guide to perioperative management for videothoracoscopy lung resection (Section of Cardiac, Vascular and Thoracic Anesthesia, SEDAR; Spanish Society of Thoracic Surgery, SECT; Spanish Society of Physiotherapy).

The introduction of video-assisted thoracoscopic (VATS) techniques has led to a new approach in thoracic surgery. VATS is performed by inserting a thoracoscope through a small incisions in the chest wall, thus maximizing the preservation of muscle and tissue. Because of its low rate of morbidity and mortality, VATS is currently the technique of choice in most thoracic procedures. Lung resection by VATS reduces prolonged air leaks, arrhythmia, pneumonia, postoperative pain and inflammatory markers. This reduction in postoperative complications shortens hospital length of stay, and is particularly beneficial in high-risk patients with low tolerance to thoracotomy. Compared with conventional thoracotomy, the oncological results of VATS surgery are similar or even superior to those of open surgery. This aim of this multidisciplinary position statement produced by the thoracic surgery working group of the Spanish Society of Anesthesiology and Reanimation (SEDAR), the Spanish Society of Thoracic Surgery (SECT), and the Spanish Association of Physiotherapy (AEF) is to standardize and disseminate a series of perioperative anaesthesia management guidelines for patients undergoing VATS lung resection surgery. Each recommendation is based on an in-depth review of the available literature by the authors. In this document, the care of patients undergoing VATS surgery is organized in sections, starting with the surgical approach, and followed by the three pillars of anaesthesia management: preoperative, intraoperative, and postoperative anaesthesia.

Unveiling gene expression regulation of the Bacillus thuringiensis Cry3Aa toxin receptor ADAM10 by the potato dietary miR171c in Colorado potato beetle.

BACKGROUND: The Colorado potato beetle (CPB) is a worldwide devastating pest of potato plants and other Solanaceae characterized by its remarkable ability to evolve resistance to insecticides. Bacillus thuringiensis (Bt) Cry3Aa toxin represents an environmentally safe alternative for CPB control but larvae susceptibility to this toxin has been reported to vary depending on the host plant on which larvae feed. To gain more insight into how nutrition mediates Bt tolerance through effects on gene expression, here we explored the post-transcriptional regulation by microRNAs (miRNAs) of the CPB-ADAM10 gene encoding the Cry3Aa toxin functional receptor ADAM10. RESULTS: The lower CPB-ADAM10 gene expression in CPB larvae fed on potato plants cv. Vivaldi than those fed on potato cv. Monalisa or tomato plants was inversely related to Cry3Aa toxicity. By high-throughput sequencing we identified seven CPB miRNAs and one potato miRNA predicted to base pair with the CPB-ADAM10 messenger RNA. No differential expression of the endogenous lde-miR1175-5p was found in larvae feeding on any of the two potato plant varieties. However, statistically significant increased amounts of potato stu-miR171c-5p were detected in CPB larvae fed on potato cv. Vivaldi compared to larvae fed on potato cv. Monalisa. CONCLUSION: Our results support a role for dietary miRNAs in Bt toxicity by regulating the CPB-ADAM10 gene encoding the Cry3Aa toxin receptor ADAM10 in CPB larvae and opening up the possibility of exploiting plant natural variation in miRNAs to provide more sustainable potato crop protection against CPB. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Urethro-venous intravasation during retrograde urethrography in a dog.

A 9-year-old 6-kg male castrated mixed-breed dog was admitted to the hospital as a second opinion for left-sided nephrectomy. Plain radiographs, ultrasound, excretory urography and retrograde urethrography revealed left-sided hydronephrosis and calculi in the bladder and urethra. The urethral calculi were hydropropulsed into the bladder and nephrectomy and cystotomy were performed. Three days after surgery, the patient showed preputial inflammation, pain and pollakiuria. Retrograde urethrography was repeated and extra-urethral leakage of contrast medium into the penile tissue was identified, followed by filling of the draining veins, reaching the caudal vena cava, with subsequent opacification of the right renal pelvis and ureter and opacification of a lymph node. The dog improved during hospitalisation and a retrograde urography performed 6 months after the initial surgery confirmed full recovery.

Clinical guide to perioperative management for videothoracoscopy lung resection (Section of Cardiac, Vascular and Thoracic Anesthesia, SEDAR; Spanish Society of Thoracic Surgery, SECT; Spanish Society of Physiotherapy). / Guía clínica en el manejo perioperatorio para la cirugía de resección pulmonar por videotoracoscopia (Sección de Anestesia Cardiaca, Vascular y Torácica, SEDAR; Sociedad Española de Cirugía Torácica, SECT; Asociación Española de Fisioterapia, AEF).

The introduction of video-assisted thoracoscopic (VATS) techniques has led to a new approach in thoracic surgery. VATS is performed by inserting a thoracoscope through a small incisions in the chest wall, thus maximizing the preservation of muscle and tissue. Because of its low rate of morbidity and mortality, VATS is currently the technique of choice in most thoracic procedures. Lung resection by VATS reduces prolonged air leaks, arrhythmia, pneumonia, postoperative pain and inflammatory markers. This reduction in postoperative complications shortens hospital length of stay, and is particularly beneficial in high-risk patients with low tolerance to thoracotomy. Compared with conventional thoracotomy, the oncological results of VATS surgery are similar or even superior to those of open surgery. This aim of this multidisciplinary position statement produced by the thoracic surgery working group of the Spanish Society of Anesthesiology and Reanimation (SEDAR), the Spanish Society of Thoracic Surgery (SECT), and the Spanish Association of Physiotherapy (AEF) is to standardize and disseminate a series of perioperative anaesthesia management guidelines for patients undergoing VATS lung resection surgery. Each recommendation is based on an in-depth review of the available literature by the authors. In this document, the care of patients undergoing VATS surgery is organized in sections, starting with the surgical approach, and followed by the three pillars of anaesthesia management: preoperative, intraoperative, and postoperative anaesthesia.

Sudden thoracic pain and paraplegia: a case of spinal cord infarction. / Dolor torácico y paraplejía de aparición súbita: un caso de infarto medular.

TITLE: Dolor torácico y paraplejía de aparición súbita: un caso de infarto medular.

Dopamine D4 Receptor Is a Regulator of Morphine-Induced Plasticity in the Rat Dorsal Striatum.

Long-term exposition to morphine elicits structural and synaptic plasticity in reward-related regions of the brain, playing a critical role in addiction. However, morphine-induced neuroadaptations in the dorsal striatum have been poorly studied despite its key function in drug-related habit learning. Here, we show that prolonged treatment with morphine triggered the retraction of the dendritic arbor and the loss of dendritic spines in the dorsal striatal projection neurons (MSNs). In an attempt to extend previous findings, we also explored whether the dopamine D4 receptor (D4R) could modulate striatal morphine-induced plasticity. The combined treatment of morphine with the D4R agonist PD168,077 produced an expansion of the MSNs dendritic arbors and restored dendritic spine density. At the electrophysiological level, PD168,077 in combination with morphine altered the electrical properties of the MSNs and decreased their excitability. Finally, results from the sustantia nigra showed that PD168,077 counteracted morphine-induced upregulation of µ opioid receptors (MOR) in striatonigral projections and downregulation of G protein-gated inward rectifier K+ channels (GIRK1 and GIRK2) in dopaminergic cells. The present results highlight the key function of D4R modulating morphine-induced plasticity in the dorsal striatum. Thus, D4R could represent a valuable pharmacological target for the safety use of morphine in pain management.

Sex Determination in Two Species of Anuran Amphibians by Magnetic Resonance Imaging and Ultrasound Techniques.

The objective of the present study was to evaluate whether gender determination in two amphibian species (Kaloula pulchra and Xenopus laevis) can be reliably carried out by means of magnetic resonance imaging (benchtop magnetic resonance imaging; BT-MRI) or ultrasound (high-resolution ultrasound; HR-US) techniques. Two species of healthy, sexually mature anurans have been used in the present study. Eight Kaloula (blind study) and six Xenopus were used as controls. Magnetic resonance imaging experiments were carried out on a low-field (1 Tesla) benchtop-MRI (BT-MRI) system. HR-US examination was performed with high-resolution equipment. Low-field BT-MRI images provided a clear and quantifiable identification of all the sexual organs present in both genders and species. The HR-US also allowed the identification of testes and ovaries in both species. Results indicate that BT-MRI allowed a very precise sex identification in both anuran species, although its use is limited by the cost of the equipment and the need for anesthesia. HR-US allowed an accurate identification of ovaries of both species whereas a precise identification of testes is limited by the ultrasonographer experience. The main advantages of this technique are the possibility of performing it without anesthesia and the higher availability of equipment in veterinary and zoo institutions.

The Histone Marks Signature in Exonic and Intronic Regions Is Relevant in Early Response of Tomato Genes to Botrytis cinerea and in miRNA Regulation.

Research into the relationship between epigenetic regulation and resistance to biotic stresses provides alternatives for plant protection and crop improvement. To unravel the mechanisms underlying tomato responses to Botrytis cinerea, we performed a chromatin immunoprecipitation (ChIP) analysis showing the increase in H3K9ac mark along the early induced genes SlyDES, SlyDOX1, and SlyLoxD encoding oxylipin-pathway enzymes, and SlyWRKY75 coding for a transcriptional regulator of hormonal signaling. This histone mark showed a more distinct distribution than the previously studied H3K4me3. The RNAPol-ChIP analysis reflected the actual gene transcription associated with increased histone modifications. A different pattern of marks in the oxylipin-related genes against P. syringae supported a pathogen-specific profile, while no significant differences occurred in SlyWRKY75. The epigenetic regulation of SlyWRKY75 by the intron-binding miR1127-3p was supported by the presence of SlyWRKY75 pre-mRNA in control plants. Interestingly, mRNA was found to be accumulated in response to B. cinerea and P. syringae, while reduction in miRNA only occurred against B. cinerea. The intronic region presented a similar pattern of marks than the rest of the gene in both pathosystems, except for H3K4me3 in the miRNA binding site upon B. cinerea. We located the gene encoding Sly-miR1127-3p, which presented reduced H3K4me3 on its promoter against B. cinerea.

[Genotype-phenotype association in a boy with neurofibromatosis type 1]. / Asociación genotipo-fenotipo en un niño con neurofibromatosis tipo 1.

TITLE: Asociación genotipo-fenotipo en un niño con neurofibromatosis tipo 1.

Proteomic insights into the immune response of the Colorado potato beetle larvae challenged with Bacillus thuringiensis.

Bacillus thuringiensis (Bt) toxins constitute effective, environmentally safe biopesticides. Nevertheless, insects' tolerance to Bt is influenced by environmental factors affecting immunity. To understand larval immune response in the devastating coleopteran insect pest Colorado potato beetle (CPB), we undertook a proteomic analysis of hemolymph of non-treated control larvae and larvae consuming non-lethal doses of spore-crystal mixtures containing the coleopteran-active Cry3Aa toxin. Results revealed lower amount of proteins involved in insect growth and higher amount of immune response-related proteins in challenged insects, sustaining the larval weight loss observed. Additionally, we found a potential regulatory role of the evolutionary conserved miR-8 in the insect's immune response relying on antimicrobial peptides (AMPs) production. Upon toxin challenge, different patterns of hemolymph AMPs expression and phenoloxidase activity were observed in CPB larvae reared on different Solanaceae plants. This suggests that diet and diet-associated insect midgut microbiota might modulate this insects' tolerance to non-lethal doses of Bt.

Colorado potato beetle chymotrypsin genes are differentially regulated in larval midgut in response to the plant defense inducer hexanoic acid or the Bacillus thuringiensis Cry3Aa toxin.

When Colorado potato beetle larvae ingested potato plants treated with the plant defense inducer compound hexanoic acid, midgut chymotrypsin enzyme activity increased, and the corresponding chymotrypsin genes were differentially expressed, evidence of the larval digestive proteolytic system's plasticity. We previously reported increased susceptibility to Cry3Aa toxin in larvae fed hexanoic acid treated plants. Here we show that the most expressed chymotrypsin gene in larvae fed hexanoic acid treated plants, CTR6, was dramatically downregulated in Cry3Aa intoxicated larvae. lde-miR-965-5p and lde-miR-9a-5p microRNAs, predicted to target CTR6, might be involved in regulating the response to hexanoic acid but not to Cry3Aa toxin.

Expression of miR159 Is Altered in Tomato Plants Undergoing Drought Stress.

In a scenario of global climate change, water scarcity is a major threat for agriculture, severely limiting crop yields. Therefore, alternatives are urgently needed for improving plant adaptation to drought stress. Among them, gene expression reprogramming by microRNAs (miRNAs) might offer a biotechnologically sound strategy. Drought-responsive miRNAs have been reported in many plant species, and some of them are known to participate in complex regulatory networks via their regulation of transcription factors involved in water stress signaling. We explored the role of miR159 in the response of Solanum lycopersicum Mill. plants to drought stress by analyzing the expression of sly-miR159 and its target SlMYB transcription factor genes in tomato plants of cv. Ailsa Craig grown in deprived water conditions or in response to mechanical damage caused by the Colorado potato beetle, a devastating insect pest of Solanaceae plants. Results showed that sly-miR159 regulatory function in the tomato plants response to distinct stresses might be mediated by differential stress-specific MYB transcription factor targeting. sly-miR159 targeting of SlMYB33 transcription factor transcript correlated with accumulation of the osmoprotective compounds proline and putrescine, which promote drought tolerance. This highlights the potential role of sly-miR159 in tomato plants' adaptation to water deficit conditions.

Identification of Stress Associated microRNAs in Solanum lycopersicum by High-Throughput Sequencing.

Tomato (Solanum lycopersicum) is one of the most important crops around the world and also a model plant to study response to stress. High-throughput sequencing was used to analyse the microRNA (miRNA) profile of tomato plants undergoing five biotic and abiotic stress conditions (drought, heat, P. syringae infection, B. cinerea infection, and herbivore insect attack with Leptinotarsa decemlineata larvae) and one chemical treatment with a plant defence inducer, hexanoic acid. We identified 104 conserved miRNAs belonging to 37 families and we predicted 61 novel tomato miRNAs. Among those 165 miRNAs, 41 were stress-responsive. Reverse transcription quantitative PCR (RT-qPCR) was used to validate high-throughput expression analysis data, confirming the expression profiles of 10 out of 11 randomly selected miRNAs. Most of the differentially expressed miRNAs were stress-specific, except for sly-miR167c-3p upregulated in B. cinerea and P. syringae infection, sly-newmiR26-3p upregulated in drought and Hx treatment samples, and sly-newmiR33-3p, sly-newmiR6-3p and sly-newmiR8-3p differentially expressed both in biotic and abiotic stresses. From mature miRNAs sequences of the 41 stress-responsive miRNAs 279 targets were predicted. An inverse correlation between the expression profiles of 4 selected miRNAs (sly-miR171a, sly-miR172c, sly-newmiR22-3p and sly-miR167c-3p) and their target genes (Kinesin, PPR, GRAS40, ABC transporter, GDP and RLP1) was confirmed by RT-qPCR. Altogether, our analysis of miRNAs in different biotic and abiotic stress conditions highlight the interest to understand the functional role of miRNAs in tomato stress response as well as their putative targets which could help to elucidate plants molecular and physiological adaptation to stress.

Pharmacological activation of dopamine D4 receptor modulates morphine-induced changes in the expression of GAD65/67 and GABAB receptors in the basal ganglia.

Dopamine D4 receptor (D4R) stimulation, in a putative D4R/µ opioid heteroreceptor (MOR) complex, counteracts the molecular, cellular and behavioural actions of morphine which are associated with morphine addiction, without any effect on its analgesic properties. In the present work, we have evaluated the role of D4R in modulating the effects of a continuous treatment with morphine on the GABAergic system in the basal ganglia. It has been demonstrated that the co-administration of a D4R agonist together with morphine leads to a restoration of GABA signaling by preventing drug-induced changes in GAD65/67 expression in the caudate putamen, globus palidus and substantia nigra. Results from GABABR1 and GABABR2 expression suggest a role of D4R in modulation of the GABAB heteroreceptor complexes along the basal ganglia, especially in the functional divisions of the caudate putamen. These results provide a new proof of the functional interaction between D4R and MOR and we postulate this putative heteroreceptor complex as a key target for the development of a new strategy to prevent the addictive effects of morphine in the treatment of pain. This article is part of the Special Issue entitled 'Receptor heteromers and their allosteric receptor-receptor interactions'.

Meningitis causada por el virus varicela-zóster en un niño inmunocompetente / Varicella-zoster virus meningitis in an immunocompetent paediatric patient

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[Acute parainfectious transverse myelitis with radiculitis in a child with closed spinal dysraphism]. / Mielitis transversa parainfecciosa aguda con radiculitis en una niña con disrafismo espinal cerrado.

TITLE: Mielitis transversa parainfecciosa aguda con radiculitis en una niña con disrafismo espinal cerrado.

Selective ablation of striatal striosomes produces the deregulation of dopamine nigrostriatal pathway.

The striatum is a complex structure in which the organization in two compartments (striosomes and matrix) have been defined by their neurochemical profile and their input-output connections. The striosomes receive afferences from the limbic brain areas and send projections to the dopamine neurons of the substantia nigra pars compacta. Thereby, it has been suggested that the striosomes exert a limbic control over the motor function mediated by the surrounding matrix. However, the functionality of the striosomes are not completely understood. To elucidate the role of the striosomes on the regulation of the nigral dopamine neurons, we have induced specific ablation of this compartment by striatal injections of the neurotoxin dermorphin-saporin (DS) and dopamine neurotransmission markers have been analyzed by immunohistochemistry. The degeneration of the striosomes resulted in a nigrostriatal projections imbalance between the two striatal compartments, with an increase of the dopamine neurotransmission in the striosomes and a decrease in the matrix. The present results highlight the key function of the striosomes for the maintenance of the striatal dopamine tone and would contribute to the understanding of their involvement in some neurological disorders such as Huntington's disease.