Respiratory syncytial virus: Clinical and epidemiological pattern in pediatric patients admitted to a children’s hospital between 2000 and 2013

INTRODUCTION: Respiratory syncytial virus (RSV) is the major causative organism associated with acute lower respiratory tract infections in children.The objective of this study was to describe the clinical and epidemiological pattern of RSV and identify risk factors for RSV infection. POPULATION AND METHODS: Prospective, cohort study on patients hospitalized due to acute lower respiratory tract infection at Hospital de Niños Ricardo Gutiérrez between March and November throughout the 2000-2013 period. The virological diagnosis of RSV, adenovirus, influenza and parainfluenza was performed by indirect immunofluorescence using nasopharyngeal aspirates. RESULTS: A total of 12,555 children were included, 38.2% (4798) had virus rescued from samples. RSV accounted for 81.8% of cases (3924/4798) with no significant annual variations (71.2- 88.1) and with an epidemic seasonal pattern(May through July); RSV was followed by influenza (7.6%), parainfluenza (5.9%), and adenovirus (4.7%).The median age of patients with RSV rescue (3924) was 7 months old (0- 214 months old), while 74.2% were younger than 1 year old, 43.1% were younger than 6 months old, 56.5% were males and the most common clinical presentation was bronchiolitis (60.7%). Comorbidities were observed in 41.6% of cases. The most common comorbidities were chronic respiratory disease (74%), congenital heart disease (14%), and chronic neurological disease (10.2%).Complications occurred in 25%of cases. The case fatality rate was 1.9% (74/3888). Independent predictors of RSV infection were age <3 months old (OR: 2.8 [2.14-3.67], p < 0.01),clinical presentation of bronchiolitis (OR: 1.54 [1.32-1.79], p < 0.01), and hypoxemia at the time of admission (OR: 1.84 [1.42-2.37], p < 0.01). CONCLUSIONS: RSV infection displayed a seasonal pattern and was associated with infants younger than 3 months old with bronchiolitis and hypoxemia at the time of admission.Fil: Lucion, María Florencia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Juárez, María del Valle. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Viegas, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castellano, Verónica. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Romanin, Viviana Sandra. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Grobaporto, Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Bakir, Julia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Mistchenko, Alicia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Laboratorio de Virología; ArgentinaFil: Gentile, Ángela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentin

Identification of promoter elements in the Dolichospermum circinale AWQC131C saxitoxin gene cluster and the experimental analysis of their use for heterologous expression

Background Dolichospermum circinale is a filamentous bloom-forming cyanobacterium responsible for biosynthesis of the paralytic shellfish toxins (PST), including saxitoxin. PSTs are neurotoxins and in their purified form are important analytical standards for monitoring the quality of water and seafood and biomedical research tools for studying neuronal sodium channels. More recently, PSTs have been recognised for their utility as local anaesthetics. Characterisation of the transcriptional elements within the saxitoxin (sxt) biosynthetic gene cluster (BGC) is a first step towards accessing these molecules for biotechnology. Results In D. circinale AWQC131C the sxt BGC is transcribed from two bidirectional promoter regions encoding five individual promoters. These promoters were identified experimentally using 5′ RACE and their activity assessed via coupling to a lux reporter system in E. coli and Synechocystis sp. PCC 6803. Transcription of the predicted drug/metabolite transporter (DMT) encoded by sxtPER was found to initiate from two promoters, PsxtPER1 and PsxtPER2. In E. coli, strong expression of lux from PsxtP, PsxtD and PsxtPER1 was observed while expression from Porf24 and PsxtPER2 was remarkably weaker. In contrast, heterologous expression in Synechocystis sp. PCC 6803 showed that expression of lux from PsxtP, PsxtPER1, and Porf24 promoters was statistically higher compared to the non-promoter control, while PsxtD showed poor activity under the described conditions. Conclusions Both of the heterologous hosts investigated in this study exhibited high expression levels from three of the five sxt promoters. These results indicate that the majority of the native sxt promoters appear active in different heterologous hosts, simplifying initial cloning efforts. Therefore, heterologous expression of the sxt BGC in either E. coli or Synechocystis could be a viable first option for producing PSTs for industrial or biomedical purposes

Burden of respiratory syncytial virus disease and mortality risk factors in Argentina: 18 years of active surveillance in a children's hospital

Background: Respiratory syncytial virus is the leading cause of acute lower respiratory infection in children. We aimed to describe the clinical-epidemiologic pattern and risk factors for mortality associated with RSV infection. Methods: This is a prospective, cross-sectional study of acute lower respiratory infection in children admitted to the Children’s Hospital during 2000 to 2017. Viral diagnosis was made by fluorescent antibody techniques or real-time-polymerase chain reaction. We compared clinical-epidemiologic characteristics of RSV infection in nonfatal versus fatal cases. Multiple logistic regression was used to identify independent predictors of mortality. Results: Of 15,451 patients with acute lower respiratory infection, 13,033 were tested for respiratory viruses and 5831 (45%) were positive: RSV 81.3% (4738), influenza 7.6% (440), parainfluenza 6.9% (402) and adenovirus 4.3% (251). RSV had a seasonal epidemic pattern coinciding with months of lowest average temperature. RSV cases show a case fatality rate of 1.7% (82/4687). Fatal cases had a higher proportion of prematurity (P < 0.01), perinatal respiratory history (P < 0.01), malnourishment (P < 0.01), congenital heart disease (P < 0.01), chronic neurologic disease (P < 0.01) and pneumonia at clinical presentation (P = 0.014). No significant difference between genders was observed. Most deaths occurred among children who had complications: respiratory distress (80.5%), nosocomial infections (45.7%), sepsis (31.7%) and atelectasis (13.4%). Independent predictors of RSV mortality were moderate-to-severe malnourishment, odds ratio (OR): 3.69 [95% confidence interval (CI): 1.98–6.87; P < 0.0001]; chronic neurologic disease, OR: 4.14 (95% CI: 2.12–8.08; P < 0.0001); congenital heart disease, OR: 4.18 (95% CI: 2.39–7.32; P< 0.0001); and the age less than 6 months, OR: 1.99 (95% CI: 1.24–3.18; P = 0.004). Conclusions: RSV showed an epidemic pattern affecting mostly young children. Malnourishment, chronic neurologic disease, congenital heart disease and the age less than 6 months were the independent risk factors for RSV mortality.Fil: Gentile, Angela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Lucion, Maria Florencia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Juarez, Maria del Valle. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Areso, María Soledad. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Bakir, Julia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Viegas, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mistchenko, Alicia Susana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Laboratorio de Virología; Argentin

The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance

In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.</p

Mini-Stern Trial: A randomised trial comparing mini-sternotomy to full median sternotomy for aortic valve replacement

Objective Aortic valve replacement (AVR) can be performed either through full median sternotomy (FS) or upper mini-sternotomy (MS). The Mini-Stern trial aimed to establish whether MS leads to quicker postoperative recovery and shorter hospital stay after first-time isolated AVR. Methods This pragmatic, open-label, parallel RCT compared MS with FS for first-time isolated AVR in two UK NHS hospitals. Primary endpoints were duration of postoperative hospital stay and the time to fitness for discharge from hospital after AVR, analysed in the intent-to-treat population. Results In this RCT, 222 patients were recruited and randomised (118 MS, 104 FS). Compared to FS patients, MS patients had longer hospital stay (mean 9.5 vs. 8.6 days) and took longer to achieve fitness for discharge home (mean 8.5 vs. 7.5 days). Adjusting for valve type, sex and surgeon, hazard ratios (HR) from Cox models did not show a statistically significant effect of MS (relative to FS) on either hospital stay (HR 0.874, 95% CI 0.668-1.143, p-value 0.3246) or time to fitness for discharge (HR 0.907, 95% CI 0.688-1.197, p-value 0.4914). During mean follow up of 760 days (MS:745 and FS:777 days), 12 (10%) MS and 7 (7%) FS patients died (HR 1.871, 95% CI 0.723-4.844, p-value 0.1966). Average extra cost for MS was £1,714, during the first 12 months after AVR. Conclusions Compared to FS for AVR, MS did not result in shorter hospital stay, faster recovery or improved survival and was not cost-effective. MS approach is not superior to FS for performing AVR

"Vad ska vi leka?" : En observationsstudie om barns könsskapande i utomhusleken och hur pedagogerna förhåller sig till detta.

Denna studies syfte var att synliggöra hur barn konstruerar kön och makt i sin lek utomhus samt hur pedagogerna förhåller sig till barns könande i lek. För att synliggöra detta har vi gjort en observationsstudie där vi observerat barngruppen och pedagogerna på en och samma förskola under deras utomhuslek inom loppet av fyra dagar. Dessa observationer delades in i två delstudier där Julia Wigren ansvarade för delstudie 1 om barnen och Selin Bakir ansvarade för delstudie 2 om pedagogerna. Under observationerna tog vi stöd av observationsmallar som vi gjort själva för att underlätta observationens syfte. Studien utgår från feministisk poststrukturalism och centrala begrepp, som makt, kön, könsroll, könsidentitet och genus för att framställa resultatet.  Resultatet av studien visar på att barn ofta valde att leka könsstereotypa lekar med barn av samma kön, samt att barnen använde sig av olika strategier för att inta maktpositioner i leken. Resultatet av pedagogernas förhållningsätt till barnens könande lek påvisade att de intog en passiv roll i den fria leken och hade ett jämlikt bemötande oavsett kön.

"Vad ska vi leka?" : En observationsstudie om barns könsskapande i utomhusleken och hur pedagogerna förhåller sig till detta.

Denna studies syfte var att synliggöra hur barn konstruerar kön och makt i sin lek utomhus samt hur pedagogerna förhåller sig till barns könande i lek. För att synliggöra detta har vi gjort en observationsstudie där vi observerat barngruppen och pedagogerna på en och samma förskola under deras utomhuslek inom loppet av fyra dagar. Dessa observationer delades in i två delstudier där Julia Wigren ansvarade för delstudie 1 om barnen och Selin Bakir ansvarade för delstudie 2 om pedagogerna. Under observationerna tog vi stöd av observationsmallar som vi gjort själva för att underlätta observationens syfte. Studien utgår från feministisk poststrukturalism och centrala begrepp, som makt, kön, könsroll, könsidentitet och genus för att framställa resultatet.  Resultatet av studien visar på att barn ofta valde att leka könsstereotypa lekar med barn av samma kön, samt att barnen använde sig av olika strategier för att inta maktpositioner i leken. Resultatet av pedagogernas förhållningsätt till barnens könande lek påvisade att de intog en passiv roll i den fria leken och hade ett jämlikt bemötande oavsett kön.

Temporal but Not Spatial Variability during Gait Is Reduced after Selective Dorsal Rhizotomy in Children with Cerebral Palsy

Introduction Variability in task output is a ubiquitous characteristic that results from non-continuous motor neuron firing during muscular force generation. However, variability can also be attributed to errors in control and coordination of the motor neurons themselves in diseases such as cerebral palsy (CP). Selective dorsal rhizotomy (SDR), a neurosurgical approach to sever sensory nerve roots, is thought to decrease redundant or excessive afferent signalling to intramedullary neurons. In addition to its demonstrated ability to reduce muscular spasticity, we hypothesised that SDR is able to decrease variability during gait, the most frequent functional motor activity of daily living. Methods Twelve CP children (aged 6.1±1.3yrs), who underwent SDR and performed gait analysis pre- and 12 months postoperatively, were compared to a control group of eleven typically developing (TD) children. Coefficients of variability as well as mean values were analysed for: temporal variables of gait, spatial parameters and velocity. Results Gait parameters of cadence (p = 0.006) and foot progression angle at mid-stance (p = 0.041) changed significantly from pre- to post-SDR. The variability of every temporal parameter was significantly reduced after SDR (p = 0.003–0.049), while it remained generally unchanged for the spatial parameters. Only a small change in gait velocity was observed, but variability in cadence was significantly reduced after SDR (p = 0.015). Almost all parameters changed with a tendency towards normal, but differences between TD and CP children remained in all parameters. Discussion The results confirm that SDR improves functional gait performance in children with CP. However, almost exclusively, parameters of temporal variability were significantly improved, leading to the conjecture that temporal variability and spatial variability may be governed independently by the motor cortex. As a result, temporal parameters of task performance may be more vulnerable to disruption, but also more responsive to treatment success of interventions such as SDR.ISSN:1932-620

Estudio clínico-epidemiológico de las infecciones respiratorias agudas bajas causadas por adenovirus en niños hospitalizados: Diecinueve años de vigilancia epidemiológica activa

Introduction. Acute lower respiratory tract infection (ALRTI) caused by adenovirus is a major cause of morbidity and mortality in children. Objectives. To describe the clinical and epidemiological pattern and associated factors in hospitalized children. Methods. Cross-sectional study in children admitted due to ALRTI to Hospital de Ninõs "Ricardo Gutiérrez," in the Autonomous City of Buenos Aires, between 2000 and 2018. Viral diagnosis was done by indirect immunofluorescence in nasopharyngeal secretions. The clinical and epidemiological characteristics of adenovirus infection were compared to other respiratory viruses (respiratory syncytial virus, influenza, and parainfluenza). A multiple logistic regression was done to identify independent predictors of infection. Results. Out of 16 018 patients with ALRTI, 13 545 were tested for respiratory viruses; 6047 (45 %) had a positive result. Adenovirus was the least common agent (4.4 % [265] of cases); it tended towards a reduction over the study period (peak in 2003) and circulated throughout the year (peak in July). In total, 63.8 % of patients were males; median age: 11 months (interquartile range: 6-20). The most common clinical presentation was pneumonia (63 %). Prior admissions due to respiratory conditions were seen in 50 %; 15.6 % were readmissions; 58.3 % had comorbidities. Ventilatory support was required by 19.2 % and complications were recorded in 44 %. The fatality rate was 7.7 %. Adenovirus infection was associated with age ≥ 12 months, male sex, clinical presentation of pneumonia, prior admissions due to respiratory conditions, and readmissions. Conclusions. Adenoviruses were less common than other respiratory viruses, although their morbidity and mortality were important.Introducción. La infección respiratoria aguda baja por adenovirus es una importante causa de morbimortalidad en niños. Objetivos: Describir el patrón clínicoepidemiológico y los factores asociados en niños hospitalizados. Métodos. Estudio transversal en niños ingresados por infección respiratoria aguda baja al Hospital de Niños Ricardo Gutiérrez, Buenos Aires, en 2000-2018. El diagnóstico viral se realizó mediante inmunofluorescencia indirecta en secreciones nasofaríngeas. Se compararon características clínico-epidemiológicas de infección por adenovirus con otros virus respiratorios (virus sincicial respiratorio, influenza y parainfluenza). Se utilizó regresión logística múltiple para identificar predictores independientes de infección. Resultados. De 16018 pacientes con infección respiratoria aguda baja, 13545 fueron testeados para virus respiratorios y 6047 (el 45 %) fueron positivos. Adenovirus fue el agente menos frecuente [el 4,4% (265) de los casos]; presentó una tendencia en descenso durante todo el período estudiado (pico en 2003) y circuló durante todo el año (pico en julio). El 63,8% eran varones; mediana de edad: 11 meses (rango intercuartílico: 6-20). La presentación clínica más frecuente fue neumonía (el 63 %). El 50 % tenía internaciones previas por causa respiratoria; el 15,6 % eran reingresos; el 58,3 % tenía comorbilidades. El 19,2 % requirió asistencia ventilatoria; el 44 % registró complicaciones. La letalidad fue del 7,7 %. La infección por adenovirus se asoció a edad ≥ 12 meses, sexo masculino, presentación clínica de neumonía, internaciones previas por causas respiratorias y reinternaciones. Conclusiones. Los adenovirus fueron detectados con menor frecuencia que los otros virus respiratorios, aunque presentaron un importante perfil de morbimortalidad.Fil: Bakir, Julia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Juarez, Maria del Valle. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Lucion, Maria Florencia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Areso, María Soledad. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Viegas, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Laboratorio de Virología; ArgentinaFil: Mistchenko, Alicia Susana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Laboratorio de Virología; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Gentile, Angela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentin