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Nogo-66 receptor 1 (NgR1) binds a variety of structurally dissimilar ligands in the adult central nervous system to inhibit axon extension. Disruption of ligand binding to NgR1 and subsequent signaling can improve neuron outgrowth, making NgR1 an important therapeutic target for diverse neurological conditions such as spinal crush injuries and Alzheimer's disease. Human NgR1 serves as a receptor for mammalian orthoreovirus (reovirus), but the mechanism of virus-receptor engagement is unknown. To elucidate how NgR1 mediates cell binding and entry of reovirus, we defined the affinity of interaction between virus and receptor, determined the structure of the virus-receptor complex, and identified residues in the receptor required for virus binding and infection. These studies revealed that central NgR1 surfaces form a bridge between two copies of viral capsid protein σ3, establishing that σ3 serves as a receptor ligand for reovirus. This unusual binding interface produces high-avidity interactions between virus and receptor to prime early entry steps. These studies refine models of reovirus cell-attachment and highlight the evolution of viruses to engage multiple receptors using distinct capsid components.
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Orthoreovirus , Reoviridae , Animais , Humanos , Receptor Nogo 1/metabolismo , Ligação Viral , Proteínas Virais/metabolismo , Ligantes , Reoviridae/metabolismo , Orthoreovirus/metabolismo , Receptores Virais/metabolismo , Mamíferos/metabolismoRESUMO
Viral nonstructural proteins, which are not packaged into virions, are essential for the replication of most viruses. Reovirus, a nonenveloped, double-stranded RNA (dsRNA) virus, encodes three nonstructural proteins that are required for viral replication and dissemination in the host. The reovirus nonstructural protein σNS is a single-stranded RNA (ssRNA)-binding protein that must be expressed in infected cells for production of viral progeny. However, the activities of σNS during individual steps of the reovirus replication cycle are poorly understood. We explored the function of σNS by disrupting its expression during infection using cells expressing a small interfering RNA (siRNA) targeting the σNS-encoding S3 gene and found that σNS is required for viral genome replication. Using complementary biochemical assays, we determined that σNS forms complexes with viral and nonviral RNAs. We also discovered, using in vitro and cell-based RNA degradation experiments, that σNS increases the RNA half-life. Cryo-electron microscopy revealed that σNS and ssRNAs organize into long, filamentous structures. Collectively, our findings indicate that σNS functions as an RNA-binding protein that increases the viral RNA half-life. These results suggest that σNS forms RNA-protein complexes in preparation for genome replication.IMPORTANCE Following infection, viruses synthesize nonstructural proteins that mediate viral replication and promote dissemination. Viruses from the family Reoviridae encode nonstructural proteins that are required for the formation of progeny viruses. Although nonstructural proteins of different viruses in the family Reoviridae diverge in primary sequence, they are functionally homologous and appear to facilitate conserved mechanisms of dsRNA virus replication. Using in vitro and cell culture approaches, we found that the mammalian reovirus nonstructural protein σNS binds and stabilizes viral RNA and is required for genome synthesis. This work contributes new knowledge about basic mechanisms of dsRNA virus replication and provides a foundation for future studies to determine how viruses in the family Reoviridae assort and replicate their genomes.
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Genoma Viral , Orthoreovirus de Mamíferos/fisiologia , RNA Viral/biossíntese , Proteínas de Ligação a RNA/metabolismo , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/fisiologia , Células HEK293 , Humanos , RNA Viral/genética , Proteínas de Ligação a RNA/genética , Proteínas não Estruturais Virais/genéticaRESUMO
The three-component apsXRS system senses and responds to cationic antimicrobial peptides (CAMPs), which induces the expression of the dlt operon and the genes mprF and vrafG, modifying the surface net charge in Staphylococcus epidermidis, resulting in the repulsion of CAMPs. The apsXRS system has been only studied in the S. epidermidis 1457 strain, and there are no studies of prevalence and level of expression of apsXRS in commensal and clinical isolates. From 60 isolates, those selected from commensal healthy skin (n = 20), commensal healthy conjunctive (n = 10), and clinical ocular infection (n = 30) presented the apsX, apsR, and apsS genes in their genomes. Constitutive expression of apsX, apsR, and apsS genes was determined by RT-qPCR in all isolates. It was found that expression of apsX, apsR, and apsS was 3.3-5.9-fold higher in commensal isolates stimulated with LL-37 (15 µg/mL) than in clinical isolates. Similarly, expression of the dlt operon and the genes mprF, and vraFG was 8-10-fold higher in commensal isolates than in clinical. However, LL-37 did not increase the addition of lysine in the phospholipids of the cytoplasmic membrane in any of the isolates. Mutations in the apsS loop region, apsR, and their promoter sequence were not found. These results demonstrated that apsXRS system is essential in all isolates for its constitutive expression; however, LL-37 caused an increase of apsXRS expression in commensal isolates, suggesting that S. epidermidis isolates do not respond in the same way to the presence of LL-37.
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A hyperthermophilic and thermostable xylanase of 82 kDa (TtXynA) was purified from the culture supernatant of T. terrestris Co3Bag1, grown on carboxymethyl cellulose (CMC), and characterized biochemically. TtXynA showed optimal xylanolytic activity at pH 5.5 and at 85 °C, and retained more than 90% of its activity at a broad pH range (4.5-10). The enzyme is highly thermostable with a half-life of 23.1 days at 65 °C, and active in the presence of several metal ions. Circular dichroism spectra strongly suggest the enzyme gains secondary structures when temperature increases. TtXynA displayed higher substrate affinity and higher catalytic efficiency towards beechwood xylan than towards birchwood xylan, oat-spelt xylan, and CMC. According to its final hydrolysis products, TtXynA displays endo-/exo-activity, yielded xylobiose, an unknown oligosaccharide containing about five residues of xylose and a small amount of xylose on beechwood xylan. Finally, this report represents the description of the first fungal hyperthermophilic xylanase which is produced by T. terrestris Co3Bag1. Since TtXynA displays relevant biochemical properties, it may be a suitable candidate for biotechnological applications carried out at high temperatures, like the enzymatic pretreatment of plant biomass for the production of bioethanol.
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Carboximetilcelulose Sódica/metabolismo , Endo-1,4-beta-Xilanases/metabolismo , Proteínas Fúngicas/metabolismo , Temperatura Alta , Microbiologia Industrial , Sordariales/enzimologia , Biomassa , Endo-1,4-beta-Xilanases/genética , Estabilidade Enzimática , Proteínas Fúngicas/genética , Sordariales/genética , Sordariales/crescimento & desenvolvimento , Sordariales/metabolismo , Especificidade por SubstratoRESUMO
Introduction. The decline in vaccination coverage has been very significant in the past decade. Pediatricians play a key role in catching-up coverage and increasing confidence in vaccination. Objectives. To describe pediatricians' perceptions of vaccine knowledge and practices and to identify barriers to access. Methods. Observational, analytical study using an online survey. Variables related to professional profile, training and barriers to vaccination were included. Results. A total of 1696 pediatricians participated (response rate: 10.7%). Their mean age was 50.4 years; 78.7% were women; 78.2% had ≥ 10 years of experience; 78.4% provided outpatient care and 56.0%, in the private subsector; and 72.5% received training in the past 2 years. Respondents described themselves as "trained" in convey the following aspects to their patients: benefits of vaccines: 97.2%; campaign objectives: 87.7%; contraindications: 82.4%; adverse effects: 78.9%; catch- up vaccination: 71.2%; reporting of events supposedly attributable to vaccination or immunization: 59.5%. The proportion was statistically higher in all aspects, among pediatricians with ≥ 10 years of experience and those who received training recently (p ≤ 0.01). The barriers identified in access to vaccination were false contraindications (62.3%), temporary vaccine shortage (46.4%), cultural reasons (41.4%), and restricted vaccination center hours (40.6%). Conclusions. The perception of the level of training varied depending on the vaccination-related aspect. Pediatricians with more years of professional experience and those who received recent updates perceived themselves as more trained. Multiple barriers associated with access to vaccination were identified.
Introducción. El descenso de las coberturas de vacunación fue muy significativo en la última década. Los pediatras son una pieza fundamental para recuperar coberturas y aumentar la confianza en la vacunación. Objetivos. Describir la percepción de los pediatras acerca del conocimiento y prácticas sobre vacunas, e identificar barreras en el acceso. Métodos. Estudio analítico observacional, mediante encuesta en línea. Se incluyeron variables del perfil del profesional, capacitación y barreras en inmunizaciones. Resultados. Participaron 1696 pediatras (tasa de respuesta: 10,7 %), media de 50,4 años. El 78,7 % fueron mujeres. El 78,2 % contaba con ≥10 años de ejercicio profesional. El 78,4 % realizaba atención ambulatoria y el 56,0 % en el subsector privado. El 72,5 % realizó una capacitación en los últimos 2 años. Se manifestaron "capacitados" para transmitir a sus pacientes los beneficios de las vacunas: 97,2 %; objetivos de campañas: 87,7 %; contraindicaciones: 82,4 %; efectos adversos: 78,9 %; recupero de esquemas: 71,2 %; notificación de ESAVI: 59,5 %. La proporción fue estadísticamente superior, en todos los aspectos, en pediatras con ≥10 años de ejercicio y en aquellos con capacitación reciente (p ≤ 0,01). Barreras identificadas en el acceso a la vacunación: falsas contraindicaciones (62,3 %); falta temporaria de vacunas (46,4 %); motivos culturales (41,4 %); horario restringido del vacunatorio (40,6 %). Conclusiones. La percepción del grado de capacitación fue variable según el aspecto de la vacunación. Aquellos con mayor tiempo de ejercicio profesional y con actualización reciente se manifestaron con mayor grado de capacidad. Se identificaron múltiples barreras frecuentes asociadas al acceso en la vacunación.
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Vacinação , Vacinas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Argentina , Pediatras , PercepçãoRESUMO
The biomass-degrading thermophilic ascomycete fungus Thielavia terrestris Co3Bag1 produces TtCel7A, a native bifunctional cellulase/xylanase GH7 family. The purified TtCel7A, with an estimated molecular weight of 71 kDa, was biochemically characterized. TtCel7A displayed an optimal pH of 5.5 for both activities and an optimal temperature of 60 and 50 °C for cellulolytic and xylanolytic activities, respectively. The half-lives determined for cellulase activity were 140, 106, and 41 min at 50, 60, and 70 °C, respectively, whereas the half-lives observed for xylanase activity were 24, 10, and 1.4 h at 50, 60, and 70 °C, respectively. The KM and Vmax values were 3.12 mg/mL and 50 U/mg for cellulase activity and 0.17 mg/mL and 42.75 U/mg for xylanase activity. Circular dichroism analysis suggests changes in the secondary structure of TtCel7A in the presence of CMC as the substrate, whereas no modifications were observed with beechwood xylan. TtCel7A displayed the excellent capability to hydrolyze CMC, beechwood xylan, and complex substrates such as oat bran, wheat bran, and sugarcane bagasse, with glucose and cellobiose being the main products released; also, slightly less endo cellulase and xylanase activities were observed. Thus, suggesting TtCel7A has an exo- and endomode of action. Based on the characteristics of the enzyme, it might be considered a good candidate for industrial applications.
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Tumor lysis syndrome is a potentially lethal complication and constitutes with infections the most frequent oncological emergency. In children, this condition can be secondary to neoplastic diseases, with corticosteroids being a triggering factor. This paper presents the case of an adolescent patient, without known or obvious neoplasms, who developed a tumor lysis syndrome after the administration of corticosteroids due to suspected respiratory infection. The clinical presentation and differential diagnoses are discussed. Special focus is placed on the administration of corticosteroids in clinical conditions with weak scientific evidence. The use of systemic corticosteroids in acute respiratory infections should be evaluated in the clinical context and only indicated in situations with proven effectiveness.
El síndrome de lisis tumoral es una complicación potencialmente letal y constituye, junto con las infecciones, la emergencia oncológica más frecuente. En pediatría, este cuadro puede ser secundario a enfermedades neoplásicas, y los corticoides son un factor desencadenante. En este trabajo se presenta el caso de una paciente adolescente, sin neoplasias conocidas o evidentes, que desarrolló un síndrome de lisis tumoral luego de la administración de corticoides por sospecha de una infección respiratoria. Se discute la forma de presentación y los diagnósticos diferenciales del cuadro clínico inicial. Se hace especial foco en la administración de corticoides en cuadros clínicos en los que no existe evidencia científica que respalde fuertemente su indicación. El uso de corticosteroides sistémicos en infecciones respiratorias agudas debe ser evaluado en el contexto clínico y solo debe indicarse en situaciones con probada efectividad.
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Síndrome de Lise Tumoral , Adolescente , Corticosteroides/efeitos adversos , Criança , Humanos , Síndrome de Lise Tumoral/diagnóstico , Síndrome de Lise Tumoral/etiologiaRESUMO
Talc is a hydrated magnesium silicate. It was part of traditional infant and young child care for decades. In children, its acute inhalation, generally accidental during diaper changes, although not frequent, is a potentially dangerous condition, and can cause severe respiratory distress and even death. We describe the case of a 14-month child who had an accidental inhalation of talc, chemical pneumonitis and severe respiratory compromise. The patient had acute respiratory distress syndrome requiring mechanical ventilation for one week. There is no standard treatment, we used systemic antibiotics and corticosteroids and aerosol therapy. He did not have complications in other organs or systems. He was hospitalized for ten days. In the follow up, he had isolated episodes of bronchial hyperresponsiveness.
El talco, un silicato de magnesio hidratado, formó parte durante décadas del cuidado tradicional de lactantes y niños pequeños. Si bien en los niños su inhalación aguda, que suele ser accidental durante el cambio de pañales, no es frecuente, es una condición potencialmente peligrosa, que puede provocar dificultad respiratoria grave e incluso cuadros mortales. Se describe el grave compromiso respiratorio por neumonitis química asociado con la inhalación accidental de talco en un lactante de 14 meses. El niño presentó un cuadro de dificultad respiratoria con requerimiento de asistencia respiratoria mecánica (ARM) durante una semana. En cuanto al tratamiento, no existe un estándar, se utilizaron antibióticos y corticoides sistémicos y aerosolterapia. No presentó complicaciones en otros órganos o sistemas. Su evolución fue favorable, se pudo externar al décimo día de internación y presentó posteriormente episodios aislados de hiperreactividad bronquial.
Assuntos
Pneumonia , Síndrome do Desconforto Respiratório , Administração por Inalação , Criança , Humanos , Lactente , Masculino , Pneumonia/induzido quimicamente , Respiração Artificial , Talco/efeitos adversosRESUMO
Escalator-related injuries are rare but can be a medical emergency with potentially dangerous complications. The severe upper limb involvement related to injury occurred on an escalator is described. A two year-old patient suffered a fall going down an escalator; her left arm was caught between one of the steps and the comb of the last step. She was admitted to the Emergency Room for the initial stabilization. The foreign body was removed in the operating room. No vascular or nervous compromise was found, but there was severe loss of subcutaneous cellular tissue. The metal comb was removed, and repair surgery was performed on the affected limb. She required four more surgical interventions for plastic and reconstructive surgery. The patient had a good clinical evolution and was discharged without functional sequelae.
Las lesiones relacionadas con escaleras mecánicas suelen ser poco frecuentes, pero pueden constituir una emergencia médica con complicaciones potencialmente peligrosas. Se describe el grave compromiso en el miembro superior relacionado con una lesión ocurrida en una escalera mecánica. Paciente de 2 años, que sufrió una caída al bajar por una escalera mecánica, y terminó con el brazo izquierdo atrapado entre uno de los escalones y los peines del descenso del escalón terminal. Ingresó a Emergencias, donde, tras realizar las medidas de estabilización inicial, se trasladó a cirugía para el retiro del cuerpo extraño. No se encontró compromiso vascular o nervioso, pero sí pérdida grave de tejido celular subcutáneo. Se retiró el peine de metal, y se realizó la cirugía reparadora del miembro afectado. Requirió cuatro intervenciones más por Cirugía Plástica y Reparadora. La paciente tuvo buena evolución clínica y recibió el alta sin secuelas funcionales.
Assuntos
Elevadores e Escadas Rolantes , Corpos Estranhos , Braço , Criança , Pré-Escolar , Emergências , Serviço Hospitalar de Emergência , Feminino , HumanosRESUMO
Diffuse pulmonary lymphangiomatosis is a rare disease characterized by marked proliferation and dilation of lymphatic vessels in the lungs, pleura, and mediastinum. The prevalence is unknown and the etiology is not fully understood. A 22-month-old girl was admitted for polyserositis, with pericardial and pleural effusion. She required pericardiocentesis and pleural drainage, presenting chyle drainage (1.5-4 liters/ day) without response to medical treatment (fasting, parenteral nutrition and octreotide). A lung biopsy was performed. The pathological anatomy showed findings compatible with diffuse pulmonary lymphangiomatosis. Treatment with sirolimus and propanolol began, decreasing losses due to pleural drainage one week after treatment. She progressed well, discontinued oxygen supply and pleural drainage was removed, leaving the patient after the fourth month of hospitalization. Early diagnosis of diffuse pulmonary lymphangiomatosis is difficult to achieve, but it allows the application of therapies that prevent disease progression, reducing morbidity and mortality.
La linfangiomatosis pulmonar difusa es una enfermedad rara caracterizada por una marcada proliferación y dilatación de los vasos linfáticos en los pulmones, la pleura y el mediastino. Se desconoce la prevalencia, y la etiología no se comprende completamente. Una niña de 22 meses ingresó por poliserositis, con derrame pericárdico y pleural. Requirió pericardiocentesis y avenamiento pleural, y presentó drenaje de quilo (1,5- 4 litros/día) sin respuesta al tratamiento médico (ayuno, nutrición parenteral y octreotide). Se realizó biopsia pulmonar. La anatomía patológica mostró hallazgos compatibles con linfangiomatosis difusa pulmonar. Comenzó tratamiento con sirolimus y propanolol, que disminuyeron las pérdidas por el drenaje pleural a la semana. Presentó buena evolución; suspendió aporte de oxígeno y se retiró el drenaje pleural. Se externó al cuarto mes de internación. El diagnóstico temprano de la linfangiomatosis pulmonar difusa es difícil de lograr, pero permite aplicar terapéuticas que evitan la progresión de enfermedad y disminuir la morbimortalidad.
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Pneumopatias , Linfangiectasia , Criança , Feminino , Humanos , Lactente , Mediastino , Pleura , TóraxRESUMO
Over the past decade, gene therapies have attracted much attention for the development of treatments for various conditions, including cancer, neurodegenerative diseases, protein deficiencies, and autoimmune disorders. Despite the benefits of this approach, several challenges are yet to be solved to reach clinical implementation. Some of these challenges include low transfection rates, limited stability under physiological conditions, and low specificity towards the target cells. An avenue to overcome such issues is to deliver the therapies with the aid of potent cell-penetrating vectors. Non-viral vectors, such as nanostructured materials, have been successfully tested in drug and gene delivery. Here, we propose the development and in vitro evaluation of a nanostructured cell-penetrating vehicle based on core/shell, magnetite/silver nanoparticles. A subsequent conjugation of a pH-responsive polymer was used to assure that the vehicle can carry and release circular DNA. Additionally, the translocating peptide Buforin II was conjugated with the aid of a polyether amine polymer to facilitate translocation and endosome escape. The obtained nanobioconjugates (magnetite/silver-pDMAEMA-PEA-BUFII) were characterized by UV-Vis spectrophotometry, dynamic light scattering (DLS), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope equipped with energy dispersive spectroscopy (SEM+EDS), and transmission electron microscopy (TEM). They were also encapsulated in lecithin liposomes to form magnetoliposomes. The cell viability of Vero cells in the presence of the nanobioconjugates was above 95% and declined to 80% for the magnetoliposomes. The hemolytic tendency of nanobioconjugates and magnetoliposomes was below 10%, while the platelet aggregation approached that of the negative control (i.e., 35%). Cytoplasm coverage values of about 50% for both Vero and neuroblastoma cells confirmed significant cell penetration. Pearson's correlation coefficients for both cell lines allowed us to estimate 20-40% colocalization of the nanobioconjugates with lysotracker green, which implied high levels of endosomal escape. The developed vehicles were also capable of loading around 16% of the added DNA and releasing such cargo with 8% efficiency. The developed nanoplatform holds a significant promise to enable highly efficient gene therapies as it overcomes some of the major issues associated with their eventual translation to the pre-clinical and clinical scale.
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Involuntary ingestion or aspiration of a brace device and/ or orthodontic arch part can constitute a medical emergency with potentially dangerous complications. The objective of this communication is to describe a rare complication of posterior displacement and ingestion of the brace arch. A 13-year-old girl, suffers from a break in orthodontia during feeding, with the subsequent ingestion of part of it. She presented dysphagia after the fact; it did not improve despite the intake of soft foods. She consulted in the Emergency Department for dysphagia, sialorrhea, pain in the pharynx and mild respiratory distress. Extraction of the orthodontic element was performed endoscopically. The embedded wire was observed at the level of the lower pole of the right amygdala and it was removed. Esophagoscopy was also performed, not observing remains of it in the esophagus. The patient was discharged without sequelae.
La ingestión involuntaria o la aspiración de un dispositivo o pieza de arco de los brackets y/u ortodoncias pueden constituir una emergencia médica con complicaciones potencialmente peligrosas. El objetivo de esta comunicación es describir una complicación poco frecuente del desplazamiento e ingesta posterior del arco de brackets. Paciente de 13 años de edad, que sufrió la ruptura de la ortodoncia durante la alimentación, con la posterior ingesta de una parte. Padeció disfagia, que no mejoró a pesar de la ingesta de alimentos blandos. Consultó en el Servicio de Emergencias y presentó disfagia, sialorrea, dolor en la faringe y dificultad respiratoria leve. Se realizó la extracción del elemento de ortodoncia por vía endoscópica; se observó el alambre incrustado a nivel del polo inferior de la amígdala derecha y se extrajo. Se realizó, además, esofagoscopía, y no se observaron restos de este en el esófago. La paciente recibió el alta sin secuelas.
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Braquetes Ortodônticos , Fios Ortodônticos , Adolescente , Feminino , HumanosRESUMO
In many viruses, including rotavirus (RV), the major pathogen of infantile gastroenteritis, capping of viral messenger RNAs is a pivotal step for efficient translation of the viral genome. In RV, VP3 caps the nascent transcripts synthesized from the genomic dsRNA segments by the RV polymerase VP1 within the particle core. Here, from cryo-electron microscopy, x-ray crystallography, and biochemical analyses, we show that VP3 forms a stable tetrameric assembly with each subunit having a modular domain organization, which uniquely integrates five distinct enzymatic steps required for capping the transcripts. In addition to the previously known guanylyl- and methyltransferase activities, we show that VP3 exhibits hitherto unsuspected RNA triphosphatase activity necessary for initiating transcript capping and RNA helicase activity likely required for separating the RNA duplex formed transiently during endogenous transcription. From our studies, we propose a new mechanism for how VP3 inside the virion core caps the nascent transcripts exiting from the polymerase.
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Rotavirus , Proteínas do Capsídeo/metabolismo , Microscopia Crioeletrônica , Genoma Viral , Nucleotidiltransferases/metabolismo , RNA Viral/genética , Rotavirus/genética , Rotavirus/metabolismo , Vírion/metabolismoRESUMO
Since the wild poliovirus no longer circulates, the number of cases of acute flaccid paralysis decreased. However, cases related to non-polio enteroviruses and neurotrope viruses continue to occur. We present a nine-year-old patient with meningitis and myelitis with motor involvement in the lower limbs and neurogenic bladder associated with enterovirus, with complete resolution of the neurological symptoms following the administration of hyperimmune gammaglobulin.
Desde la eliminación de la circulación del virus polio salvaje, disminuyeron los casos de parálisis fláccida aguda. Sin embargo, continúan ocurriendo casos asociados a otros enterovirus no polio y virus neurotropos. Se presenta el caso de una paciente de 9 años con diagnóstico de meningitis y mielitis con compromiso motor en los miembros inferiores y vejiga neurogénica asociado a enterovirus, con resolución completa del cuadro neurológico posterior a la administración de gammaglobulina hiperinmune.
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Infecções por Enterovirus/diagnóstico , Meningite Viral/virologia , Mielite/virologia , Paralisia/virologia , Criança , Infecções por Enterovirus/tratamento farmacológico , Infecções por Enterovirus/patologia , Feminino , Humanos , Meningite Viral/tratamento farmacológico , Mielite/tratamento farmacológico , Paralisia/tratamento farmacológico , Bexiga Urinaria Neurogênica/tratamento farmacológico , Bexiga Urinaria Neurogênica/virologia , gama-Globulinas/administração & dosagemRESUMO
INTRODUCTION: Severe sepsis (SS) is one of the leading causes of pediatric mortality in Argentina. The objective was to describe the epidemiological characteristics and to analyze risk factors associated with mortality from SS among patients hospitalized in pediatric intensive care units (PICU) in Argentina. POPULATION AND METHODS: Observational, prospective cohort study among patients with SS hospitalized in PICUs in Argentina from 8/1/2008 to 9/30/2008. RESULTS: Two thousand five hundred and fifty nine patients were admitted at 59 PICUs. A total of 315 patients (335 events) were included. Patients' median age was 8 months (1-182). The frequency was 13.8 %, and 28-day mortality was 31.6 %. Patients with a higher mortality were those who were coming from rural areas, had comorbidities at the time of admission or a history of cancer, had shock or acute respiratory distress syndrome (ARDS), were administered low-dose corticosteroids or vasoactive drugs or more than 60 ml/kg of fluid in the first hour and in the first 6hours, and had severe malnutrition. Following adjustment by severity using a multivariate logistic regression model, only coming from a rural area, having shock or ARDS remained associated with 28-day mortality. Forty per cent of patients received antibiotics 60 minutes after diagnosis. CONCLUSIONS: SS is an event with a high frequency and mortality in Argentina. In the severity adjusted multivariate analysis, only coming from a rural area, having ARDS and/or shock were associated with higher mortality.
Introducción. La sepsis grave (SG) es una de las principales causas de mortalidad pediátrica en Argentina. El objetivo fue describir las características epidemiológicas y analizar los factores asociados a la mortalidad de la SG en pacientes internados en unidades de cuidados intensivos pediátricos (UCIP) de Argentina. Pacientes y métodos. Estudio observacional, de cohorte prospectiva en pacientes con SG internados en UCIP de Argentina del 1/8/2008 al 30/9/2008. Resultados. En 59 UCIP, ingresaron 2559 pacientes. Se incluyeron 315 pacientes, que tuvieron 335 eventos. La mediana de edad fue 8 meses (1-182). La frecuencia fue del 13,8 % y la mortalidad a los 28 días, del 31,6 %. Tuvieron mayor mortalidad quienes procedían del ámbito rural, presentaban una comorbilidad al ingresar o antecedentes oncológicos, tenían shock o síndrome de dificultad respiratoria aguda (SDRA), recibieron corticoides en bajas dosis o drogas vasoactivas o más de 60 ml/kg de fluidos en la primera hora y en las 6 primeras horas, y los desnutridos graves. Al ajustarse por gravedad en un modelo de regresión logística multivariado, solo mantuvieron la asociación con mortalidad a los 28 días el provenir del ámbito rural, tener shock o SDRA. El 40 % de los pacientes recibieron antibióticos después de los 60 minutos del diagnóstico. Conclusiones. La SG es un evento de elevada frecuencia y mortalidad en Argentina. En el análisis multivariado ajustado por gravedad, solo provenir del área rural, la presencia de SDRA y/o de shock se asociaron a mayor mortalidad.
Assuntos
Mortalidade Hospitalar , Sepse/epidemiologia , Adolescente , Argentina/epidemiologia , Criança , Pré-Escolar , Feminino , Hidratação , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Masculino , Neoplasias/epidemiologia , Estado Nutricional , Estudos Prospectivos , Análise de Regressão , Síndrome do Desconforto Respiratório/epidemiologia , Fatores de Risco , População Rural/estatística & dados numéricos , Sepse/mortalidade , Sepse/terapiaRESUMO
Introducción. El descenso de las coberturas de vacunación fue muy significativo en la última década. Los pediatras son una pieza fundamental para recuperar coberturas y aumentar la confianza en la vacunación. Objetivos. Describir la percepción de los pediatras acerca del conocimiento y prácticas sobre vacunas, e identificar barreras en el acceso. Métodos. Estudio analítico observacional, mediante encuesta en línea. Se incluyeron variables del perfil del profesional, capacitación y barreras en inmunizaciones. Resultados. Participaron 1696 pediatras (tasa de respuesta: 10,7 %), media de 50,4 años. El 78,7 % fueron mujeres. El 78,2 % contaba con ≥10 años de ejercicio profesional. El 78,4 % realizaba atención ambulatoria y el 56,0 % en el subsector privado. El 72,5 % realizó una capacitación en los últimos 2 años. Se manifestaron "capacitados" para transmitir a sus pacientes los beneficios de las vacunas: 97,2 %; objetivos de campañas: 87,7 %; contraindicaciones: 82,4 %; efectos adversos: 78,9 %; recupero de esquemas: 71,2 %; notificación de ESAVI: 59,5 %. La proporción fue estadísticamente superior, en todos los aspectos, en pediatras con ≥10 años de ejercicio y en aquellos con capacitación reciente (p ≤ 0,01). Barreras identificadas en el acceso a la vacunación: falsas contraindicaciones (62,3 %); falta temporaria de vacunas (46,4 %); motivos culturales (41,4 %); horario restringido del vacunatorio (40,6 %). Conclusiones. La percepción del grado de capacitación fue variable según el aspecto de la vacunación. Aquellos con mayor tiempo de ejercicio profesional y con actualización reciente se manifestaron con mayor grado de capacidad. Se identificaron múltiples barreras frecuentes asociadas al acceso en la vacunación.
Introduction. The decline in vaccination coverage has been very significant in the past decade. Pediatriciansplay a key role in catching-up coverage and increasing confidence in vaccination. Objectives. To describe pediatricians' perceptions of vaccine knowledge and practices and to identify barriers to access. Methods. Observational, analytical study using an online survey. Variables related to professional profile, training and barriers to vaccination were included. Results. A total of 1696 pediatricians participated (response rate: 10.7%). Their mean age was 50.4 years; 78.7% were women; 78.2% had ≥ 10 years of experience; 78.4% provided outpatient care and 56.0%, in the private subsector; and 72.5% received training in the past 2 years. Respondents described themselves as "trained" in convey the following aspects to their patients: benefits of vaccines: 97.2%; campaign objectives: 87.7%; contraindications: 82.4%; adverse effects: 78.9%; catchup vaccination: 71.2%; reporting of events supposedly attributable to vaccination or immunization: 59.5%. The proportion was statistically higher in all aspects, among pediatricians with ≥ 10 years of experience and those who received training recently (p ≤ 0.01). The barriers identified in access to vaccination were false contraindications (62.3%), temporary vaccine shortage (46.4%), cultural reasons (41.4%), and restricted vaccination center hours (40.6%). Conclusions. The perception of the level of training varied depending on the vaccination-related aspect. Pediatricians with more years of professional experience and those who received recent updates perceivedthemselves as more trained. Multiple barriers associated with access to vaccination were identified.
Assuntos
Humanos , Pessoa de Meia-Idade , Vacinas , Vacinação , Percepção , Argentina , Inquéritos e Questionários , PediatrasRESUMO
El síndrome de lisis tumoral es una complicación potencialmente letal y constituye, junto con las infecciones, la emergencia oncológica más frecuente. En pediatría, este cuadro puede ser secundario a enfermedades neoplásicas, y los corticoides son un factor desencadenante. En este trabajo se presenta el caso de una paciente adolescente, sin neoplasias conocidas o evidentes, que desarrolló un síndrome de lisis tumoral luego de la administración de corticoides por sospecha de una infección respiratoria. Se discute la forma de presentación y los diagnósticos diferenciales del cuadro clínico inicial. Se hace especial foco en la administración de corticoides en cuadros clínicos en los que no existe evidencia científica que respalde fuertemente su indicación. El uso de corticosteroides sistémicos en infecciones respiratorias agudas debe ser evaluado en el contexto clínico y solo debe indicarse en situaciones con probada efectividad.
Tumor lysis syndrome is a potentially lethal complication and constitutes with infections the most frequent oncological emergency. In children, this condition can be secondary to neoplastic diseases, with corticosteroids being a triggering factor. This paper presents the case of an adolescent patient, without known or obvious neoplasms, who developed a tumor lysis syndrome after the administration of corticosteroids due to suspected respiratory infection.The clinical presentation and differential diagnoses are discussed. Special focus is placed on the administration of corticosteroids in clinical conditions with weak scientific evidence. The use of systemic corticosteroids in acute respiratory infections should be evaluated in the clinical context and only indicated in situations with proven effectiveness.
Assuntos
Humanos , Feminino , Adolescente , Síndrome de Lise Tumoral/diagnóstico , Síndrome de Lise Tumoral/etiologia , Corticosteroides/efeitos adversosRESUMO
Small heat shock proteins are ubiquitous molecular chaperones that form the first line of defence against the detrimental effects of cellular stress. Under conditions of stress they undergo drastic conformational rearrangements in order to bind to misfolded substrate proteins and prevent cellular protein aggregation. Owing to the dynamic nature of small heat shock protein oligomers, elucidating the structural basis of chaperone action and oligomerization still remains a challenge. In order to understand the organization of sHSP oligomers, we have determined crystal structures of a small heat shock protein from Salmonella typhimurium in a dimeric form and two higher oligomeric forms: an 18-mer and a 24-mer. Though the core dimer structure is conserved in all the forms, structural heterogeneity arises due to variation in the terminal regions.
Assuntos
Proteínas de Bactérias/química , Proteínas de Choque Térmico/química , Conformação Proteica , Multimerização Proteica , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Microscopia Crioeletrônica , Cristalografia por Raios X , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Modelos Moleculares , Mutação , Ligação Proteica , Dobramento de Proteína , Subunidades Proteicas/química , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismo , Homologia de Sequência de Aminoácidos , Soluções/químicaRESUMO
El talco, un silicato de magnesio hidratado, formó parte durante décadas del cuidado tradicional de lactantes y niños pequeños. Si bien en los niños su inhalación aguda, que suele ser accidental durante el cambio de pañales, no es frecuente, es una condición potencialmente peligrosa, que puede provocar dificultad respiratoria grave e incluso cuadros mortales. Se describe el grave compromiso respiratorio por neumonitis química asociado con la inhalación accidental de talco en un lactante de 14 meses. El niño presentó un cuadro de dificultad respiratoria con requerimiento de asistencia respiratoria mecánica (ARM) durante una semana. En cuanto al tratamiento, no existe un estándar, se utilizaron antibióticos y corticoides sistémicos y aerosolterapia. No presentó complicaciones en otros órganos o sistemas. Su evolución fue favorable, se pudo externar al décimo día de internación y presentó posteriormente episodios aislados de hiperreactividad bronquial.
Talc is a hydrated magnesium silicate. It was part of traditional infant and young child care for decades. In children, its acute inhalation, generally accidental during diaper changes, although not frequent, is a potentially dangerous condition, and can cause severe respiratory distress and even death. We describe the case of a 14-month child who had an accidental inhalation of talc, chemical pneumonitis and severe respiratory compromise. The patient had acute respiratory distress syndrome requiring mechanical ventilation for one week. There is no standard treatment, we used systemic antibiotics and corticosteroids and aerosol therapy. He did not have complications in other organs or systems. He was hospitalized for ten days. In the follow up, he had isolated episodes of bronchial hyperresponsiveness.