In vitro reconstitution reveals membrane clustering and RNA recruitment by the enteroviral AAA+ ATPase 2C.

Enteroviruses are a vast genus of positive-sense RNA viruses that cause diseases ranging from common cold to poliomyelitis and viral myocarditis. They encode a membrane-bound AAA+ ATPase, 2C, that has been suggested to serve several roles in virus replication, e.g. as an RNA helicase and capsid assembly factor. Here, we report the reconstitution of full-length, poliovirus 2C's association with membranes. We show that the N-terminal membrane-binding domain of 2C contains a conserved glycine, which is suggested by structure predictions to divide the domain into two amphipathic helix regions, which we name AH1 and AH2. AH2 is the main mediator of 2C oligomerization, and is necessary and sufficient for its membrane binding. AH1 is the main mediator of a novel function of 2C: clustering of membranes. Cryo-electron tomography reveal that several 2C copies mediate this function by localizing to vesicle-vesicle interfaces. 2C-mediated clustering is partially outcompeted by RNA, suggesting a way by which 2C can switch from an early role in coalescing replication organelles and lipid droplets, to a later role where 2C assists RNA replication and particle assembly. 2C is sufficient to recruit RNA to membranes, with a preference for double-stranded RNA (the replicating form of the viral genome). Finally, the in vitro reconstitution revealed that full-length, membrane-bound 2C has ATPase activity and ATP-independent, single-strand ribonuclease activity, but no detectable helicase activity. Together, this study suggests novel roles for 2C in membrane clustering, RNA membrane recruitment and cleavage, and calls into question a role of 2C as an RNA helicase. The reconstitution of functional, 2C-decorated vesicles provides a platform for further biochemical studies into this protein and its roles in enterovirus replication.

Using Latent Profile Analysis to Characterize Clinical Heterogeneity and Impulsivity in a Large Residential Addiction Treatment Program.

Objectives: Clinical heterogeneity among patients in addiction treatment settings represents a challenge as most of the treatment programs are designed to treat substance use disorders (SUD) generally rather than offering more tailored approaches addressing individual patient needs. Systematic characterization of clinical heterogeneity may permit more individualized care paths toward improving outcomes. Methods: Data were collected from a large inpatient SUD treatment program between April 2018 and March 2020 (n = 1519). Latent profile analysis (LPA) was applied to identify latent clusters based on differences in substance use and co-occurring depression, anxiety, and post-traumatic stress disorder. Results: Five distinct profiles emerged: Profile 1 (38%) exhibited the lowest substance use and lowest psychiatric severity (Overall Low); Profile 2 (39%) exhibited high alcohol and psychiatric severity; Profile 3 (13%) exhibited high opioid severity and low psychiatric severity. Profile 4 (8%) exhibited high cannabis use and high psychiatric severity, and profile 5 (3%) exhibited high polysubstance use other than alcohol and cannabis use. The latter two profiles were younger and exhibited higher self-regulatory deficits. The (High Alc/high psych) and the (High Cann/Psych) profiles exhibited differentially higher psychiatric severity. Profiles showing high polysubstance use, as well as high cannabis use and high psychiatric severity, showed significantly higher impulsive behavior than the others. Conclusions: LPA revealed five clusters of patients varying substantially in terms of SUD and psychiatric severity. Addressing common features of clinical heterogeneity for tailored care paths in a personalized treatment approach may improve treatment outcomes.

Long-term hearing prognosis after vestibular schwannoma surgery with retrolabyrinthine approach.

PURPOSE: The retrolabyrinthine approach is a surgical method designed to preserve hearing after surgery. When paired with intraoperative monitoring and an endoscope, this approach has demonstrated high rates of postoperative hearing preservation. However, the long-term prognosis of hearing preservation after utilizing this approach for vestibular schwannomas remains unexplored. This study aimed to examine the long-term outcomes of preserved hearing, providing insights into the suitability of the retrolabyrinthine approach for hearing preservation surgery. METHODS: This study included 34 patients with preserved hearing after vestibular schwannoma surgery using the retrolabyrinthine approach at a single center. Long-term hearing prognosis and requirement for additional interventions were retrospectively examined. RESULTS: Immediate after post-operative hearing preservation rate was 71.7%. Among the 34 patients with preserved hearing post-vestibular schwannoma surgery, four (11.8%) required additional interventions. Other patients experienced a gradual deterioration in their hearing status, with an approximate 10 dB decline during the 5-year follow-up; however, a serviceable hearing level persisted long after the surgery in these individuals. CONCLUSIONS: This study indicated the rationale for the retrolabyrinthine approach as a hearing preservation surgery for vestibular schwannomas, emphasizing its long-term hearing prognosis.

Same but different - pseudo-pectin in the charophytic alga Chlorokybus atmophyticus.

All land-plant cell walls possess hemicelluloses, cellulose and anionic pectin. The walls of their cousins, the charophytic algae, exhibit some similarities to land plants' but also major differences. Charophyte 'pectins' are extractable by conventional land-plant methods, although they differ significantly in composition. Here, we explore 'pectins' of an early-diverging charophyte, Chlorokybus atmophyticus, characterising the anionic polysaccharides that may be comparable to 'pectins' in other streptophytes. Chlorokybus 'pectin' was anionic and upon acid hydrolysis gave GlcA, GalA and sulphate, plus neutral sugars (Ara≈Glc>Gal>Xyl); Rha was undetectable. Most Gal was the l-enantiomer. A relatively acid-resistant disaccharide was characterised as ß-d-GlcA-(1→4)-l-Gal. Two Chlorokybus 'pectin' fractions, separable by anion-exchange chromatography, had similar sugar compositions but different sulphate-ester contents. No sugars were released from Chlorokybus 'pectin' by several endo-hydrolases [(1,5)-α-l-arabinanase, (1,4)-ß-d-galactanase, (1,4)-ß-d-xylanase, endo-polygalacturonase] and exo-hydrolases [α- and ß-d-galactosidases, α-(1,6)-d-xylosidase]. 'Driselase', which hydrolyses most land-plant cell wall polysaccharides to mono- and disaccharides, released no sugars except traces of starch-derived Glc. Thus, the Ara, Gal, Xyl and GalA of Chlorokybus 'pectin' were not non-reducing termini with configurations familiar from land-plant polysaccharides (α-l-Araf, α- and ß-d-Galp, α- and ß-d-Xylp and α-d-GalpA), nor mid-chain residues of α-(1→5)-l-arabinan, ß-(1→4)-d-galactan, ß-(1→4)-d-xylan or α-(1→4)-d-galacturonan. In conclusion, Chlorokybus possesses anionic 'pectic' polysaccharides, possibly fulfilling pectic roles but differing fundamentally from land-plant pectin. Thus, the evolution of land-plant pectin since the last common ancestor of Chlorokybus and land plants is a long and meandering path involving loss of sulphate, most l-Gal and most d-GlcA; re-configuration of Ara, Xyl and GalA; and gain of Rha.

Significações culturais e simbólicas da dança do Maculelê do Balé Folclórico da Bahia / Cultural and symbolic meanings of the Maculelê Dance of the Folkloric Ballet of Bahia / Cultural and symbolic meanings of the Maculelê Dance of the Folkloric Ballet of Bahia

Este ensaio tem como objetivo descrever e refletir sobre o universo simbólico e cultural da coreografia Maculelê apresentada pelo Balé Folclórico da Bahia (BFBA), no espetáculo Herança Sagrada. Partimos da descrição das cenas dessa coreografia, incluindo os gestos, os figurinos, a formação dos bailarinos e as letras das músicas, que em conjunto construíram uma rede de significados que permitiu identificar os símbolos culturais inscritos nessa versão da referida manifestação da cultura popular, que serviu de inspiração para o espetáculo artístico do grupo baiano. As impressões culturais e simbólicas permitidas na cena do Maculelê do BFBA variaram desde a formação dos bailarinos no palco até os cânticos entoados por eles e foram discutidas utilizando os principais autores que dialogam com os temas, conforme eles foram surgindo. Esses diálogos entre obra artística e autores, mediados no presente ensaio, permitiram ampliar a reflexão simbólica e cultural presente nas danças afro-brasileiras, entendendo-as como campo fértil que permite se apropriar do conhecimento sensível e aberto que a dança proporciona, promovendo uma educação livre de determinismos e reducionismos. Desse modo, a visão de corpo é também ampliada, ajudando a compreendê-lo livre de simplificações pré-determinadas que o assemelha a uma simples máquina, mas que considera seus simbolismos e sua capacidade sensível e expressiva, tornando-o sujeito, obra de arte em constante troca e construção...(AU)

This essay aims to describe and reflect on the symbolic and cultural universe of the Maculelê choreography presented by the Folkloric Ballet of Bahia (BFBA), in the show Sacred Heritage. We started with the description of the scenes of this choreography, including the gestures, the costumes, the training of the dancers and the lyrics of the songs, which together built a network of meanings that allowed the identification of the cultural symbols inscribed in this version of the popular manifestation of culture. served as inspiration for the artistic performance of the Bahian group. The cultural and symbolic impressions allowed in the BFBA Maculelê scene varied from the formation of the dancers on stage to the chants they sang and were discussed using the main authors who dialogued with the themes as they emerged. These dialogues between artistic work and authors, mediated in the present essay, have allowed to broaden the symbolic and cultural reflection present in the Afro-Brazilian dances, understanding them as a fertile field that allows to appropriate the sensitive and open knowledge that the dance provides, promoting an education free from determinism and reductionism. In this way, the body view is also enlarged, helping to understand it free of predetermined simplifications that resemble it to a simple machine, but which considers its symbolism and its sensitive and expressive capacity, making it subject, a work of art in constant exchange and construction...(AU)

Ventilación no invasiva en menores de dos años internados en sala con infección respiratoria aguda baja. Posibles factores predictivos de éxito y de fracaso / Non invasive ventilation in children under two years interned in room with acute lower respiratory infection. Possible predictors of success and failure

Objetivos: describir los resultados de la aplicación de ventilación no invasiva en los años 2009 y 2010 en niños menores de dos años con infección respiratoria aguda baja y analizar posibles factores predictivos de éxito o fracaso. Diseño: observacional, prospectivo, analítico. Población: menores de 2 años cursando IRAB con insuficiencia respiratoria y escore de Tal >= 8, o Tal >= 6 sin respuesta al tratamiento. Se excluyeron aquellos con peso < 7 kg, hemodinamia inestable, depresión neuropsíquica, neumotórax, neumomediastino y/oacidosis mixta. Resultados: se incluyeron 185 niños, mediana de edad 9 meses, peso promedio 8,6 kg. Se constató éxito en 151 niños (81,6%). No se observaron diferencias estadísticamente significativas en la edad, peso y severidad al ingreso entre el grupo de niñoscon éxito versus fracaso terapéutico. A las 2 horas la frecuencia respiratoria (FR) mayor a 60 rpm, la frecuencia cardíaca (FC) mayor 140 cpm y la presión de soporte mayor a 9 se asoció con fracaso (p<0,05).El análisis multivariado mostró que a las 2 h la FR > 60rpm incrementó el riego de fracaso 6.4 veces (IC951,9–21,7); la FC > 140 cpm 4,3 (IC95 1,5-11,8) y la PS>9 lo incrementó 8,7 veces (IC95 2,3-32,2). Conclusión: el aumento de la FR, la FC y la PS a las 2 horas constituyen posibles factores predictivos de fracaso terapéutico. Futuras investigaciones son necesarias para confirmar estos hallazgos e individualizar las indicaciones de esta técnica en estos pacientes.

Afectación cardíaca en el curso de infecciones respiratorias agudas virales: reporte preliminar / Cardiac involvement during acute viral respiratory infections: preliminary report

Las infecciones respiratorias agudas bajas virales constituyen una de las causas más importantes de enfermedad y muerte en niños en todo el mundo. En Uruguay las infecciones respiratorias agudas constituyen la causa más frecuente de admisión hospitalaria en los meses fríos y una causa prevalente de ingreso a cuidados intensivos. La afectación miocárdica ha sido descrita como complicación determinante en la evolución de la enfermedad. Objetivos: conocer la prevalencia y gravedad de la afectación cardíaca en el curso de las infecciones respiratorias agudas bajas virales y evaluar la utilidad de la troponina T para despistar compromiso miocárdico. Material y métodos: estudio descriptivo prospectivo. Se incluyeron lactantes portadores de infecciones respiratorias agudas bajas virales admitidas al hospital. Se realizó en todos los pacientes estudio radiológico de tórax, ECG, test de troponina T sérica y ecocardiograma. Se realizó seguimiento a los que presentaron afectación en el ECG, ECO o en el test de troponina. Resultados: se incluyeron 80 pacientes. El virus sincicial respiratorio (VRS) fue la etiología en el 53%. El ECG evidenció alteraciones inespecíficas de la repolarización en el 17% de los casos Se describió la presencia de derrame pericárdico en el 9% de los casos. Estas alteraciones no se asociaron con la gravedad ni la etiología. La troponina estuvo aumentada en el 4% sin asociaciones significativas con las variables analizadas. La CPK en estos pacientes fue normal. No hubo muertes en esta muestra. Conclusiones: se evidenciaron frecuentes alteraciones cardíacas por el ECG y el ECO que no se asociaron con requerimiento de cuidados intensivos o ventilación mecánica. La troponina estuvo aumentada en el 4% de los casos, lo que se considera una prevalencia menor a lo referido en la bibliografía, lo que no se vinculó con la evolución de los pacientes.

Acute viral respiratory infections are one of the most important causes of illness and death in children around the world. In Uruguay, acute respiratory infections are the cause of hospital admissions in the cold months and a prevalent admission cause to be admitted in intensive care. Myocardial involvement has been described as a major complication in the evolution of the disease. Objectives: to know the prevalence and severity of heart illness in the course of the low viral load acute respiratory infections and assess the usefulness of troponin T to find myocardial compromise. Material and methods: prospective descriptive study. We included IRABV carriers, admitted to the hospital, of up to two years. All RX chest, ECG, troponin T serum and Echocardiogram tests performed. Follow-up to those which presented affectation ECG, ECO or troponin test took place. Results: 80 patients were included. VRS was the etiology in 53%. The ECG evidenced unspecific alterations of the repolarization in 17%. The presence of pericardial effusion was described in 9% of cases. These alterations were not associated with the seriousness or etiology. Troponin was increased by 4% without significant association with the analyzed variables. CPK in these patients was normal. There were no deaths in this sample. Conclusions: frequent heart alterations by the ECG and ECO became apparent but were not associated with requirements of intensive care or mechanical ventilation. Troponin was increased in 4 per cent of cases but it was not linked to the evolution of patients.

Implementación de una unidad de vigilancia respiratoria para la asistencia de niños con infección respiratoria aguda baja en el hospital pediátrico del Centro Hospitalario Pereira Rossell / Implementation of a respiratory care unit for care of children with acute low respiratory infection in the Centro Hospitalario Pereira Rossell

Introducción: durante la estrategia Plan de Invierno 2008 del Hospital Pediátrico del Centro Hospitalario Pereira Rossell se implementó una Unidad de Vigilancia Respiratoria (UVR) para brindar una atención más individualizada al niño con infección respiratoria aguda baja (IRAB) grave.Objetivo: evaluar los resultados de la implementación de la UVR. Material y método: la unidad funcionó del 17 de junio al 31 de agosto de 2009; contó con 6 camas y personal médico, enfermería y fisioterapeutas durante las 24 horas. Los criterios de ingreso fueron: edad < 2 años, insuficiencia respiratoria y escore de Tal > 9. Los criterios de exclusión: hemodinamia inestable, alteración de la conciencia, complicaciones mecánicas, acidosis respiratoria o mixta. Todos los pacientes recibieron el mismo tratamiento de soporte. Se analiza el número de ingresos, sus características clínicas y evolutivas. Resultados: ingresaron 147 niños, 5,4% del total de admisiones hospitalarias por IRAB. El 62% fueron £ 6 meses, edad promedio 5,9 meses. Se diagnosticó bronquiolitis en 71%, presentaron escore de Tal ³ 6 el 63,9%. La estadía promedio fue 4 días; en 37% £ 24 horas. Presentaron evolución favorable 69,4%, y se trasladaron a CTI 30,6% (n45), de los cuales 27 requirieron soporte ventilatorio y uno falleció.Conclusiones: la atención .individualizada de soporte del niño con IRAB resulta fundamental. Es necesario jerarquizar la edad como factor de riesgo y la monitorización clínica a través de escores que evalúan el trabajo respiratorio. Si bien no se puede afirmar que la UVR contribuyó a disminuir los ingresos a CTI, la experiencia resultó beneficiosa y fortaleció la estrategia de atención del niño con IRAB grave.

Introduction: a Respiratory Surveillance Unit (RSU) was implemented together with the 2008 Winter Plan of the Pediatric Hospital of the Pereira Rossell Hospital Centre to provide more personalized care to children with severe Acute Low Respiratory Infection (ALRI). Objective: evaluate the outcomes of the implementation of the RSU. Methodology: the unit worked from 17-6 to 31-10-08 and counted with 6 beds and medical and nursing staff and physical therapists around the clock. Admission criteria were: age < 2 years, respiratory failure, Tal score > 9. Exclusion criteria: unstable hemodynamics, consciousness disorders, mechanical complications, respiratory or mixed acidosis. All patients received the same support treatment. The number of admissions, their characteristics and course were all analyzed. Results: a total 147 children were admitted, 5.4% of the total hospital admissions due to ALRI. A 62% were < of 6 months, average age 5.9 months. Bronchiolitis was diagnosed in 71% and 63.9% presented the Tal 6 score. The average duration of stay was 4 days and 24 hours in 37%. A 69.4% presented a favorable course; 30.6% (n=45) were sent to the ICU, 27 of whom required ventilatory support, and one died. Conclusions: individualized support care is essential in children with ALRI. It is necessary to to prioritize age as a risk factor, and clinical monitoring by means of scores evaluating respiratory work. Although it is not possible to state that the RSU contributed to reduce admissions to the ICU, the experience was beneficial and strengthened the care strategy for children with severe ALRI.

Infecciones de piel y partes blandas en pacientes ambulatorios / Skin and soft tissue infection in outpatients

Introducción: en la última década se ha informado a nivel mundial la emergencia de infecciones causadas por cepas de Staphylococcus aureus meticilino-resistente (SAMR) sin los factores de riesgo clásicos descriptos para portar este germen, con un patrón de susceptibilidad diferente a los antibióticos y adquirido en la comunidad. En nuestro país las primeras comunicaciones de infecciones producidas por este germen fueron en el año 2001 en niños con infecciones de piel y partes blandas internados en el Centro Hospitalario Pereira Rossell (CHPR).Objetivo: 1) Analizar las características clínicas y la etiología de las infecciones de piel y partes blandas en pacientes ambulatorios. 2) Determinar en estas infecciones la prevalencia de Staphylococcus aureus meticilino-resistente adquirido en la comunidad (SAMR-com) y su sensibilidad a los antibióticos. Material y métodos: se realizó un estudio descriptivo, prospectivo, de pacientes que consultaron en el Departamento de Emergencia Pediátrica del CHPR por infecciones de piel y partes blandas adquiridas en la comunidad, en el período 24 de marzo de 2004 al 31 de julio de 2004, tratados en forma ambulatoria y en los que se aisló una bacteria de las muestras obtenidas para estudio bacteriológico. Se incluyeron pacientes con impétigo, forúnculo, absceso, celulitis a punto de partida cutáneo, panadizo y herida o quemadura sobreinfectada. Se analizaron datos demográficos, factores de riesgo para portar SAMR, características clínicas de los pacientes y análisis bacteriológico de los resultados de las muestras obtenidas de acuerdo al informe realizado por el Laboratorio Central del CHPR, sección Bacteriología. Resultados: se incluyeron 297 pacientes. Los diagnósticos clínicos realizados fueron: impétigo 122 (48,4 por ciento), forúnculo 29 (11,5 por ciento), celulitis 19 (7,5 por ciento), absceso 30 (11,9 por ciento), panadizo ocho (3,2 por ciento), heridas o quemaduras infectadas seis (2,4 por ciento) y coexistencia de alguna...