Failure of early non-invasive ventilation in preterm infants with respiratory distress syndrome in current care practice in Spanish level-III neonatal intensive care units - a prospective observational study.

Introduction: Despite advances in respiratory distress syndrome (RDS) management over the past decade, non-invasive ventilation (NIV) failure is frequent and associated with adverse outcomes. There are insufficient data on the failure of different NIV strategies currently used in clinical practice in preterm infants. Methods: This was a prospective, multicenter, observational study of very preterm infants [gestational age (GA) <32 weeks] admitted to the neonatal intensive care unit for RDS that required NIV from the first 30 min after birth. The primary outcome was the incidence of NIV failure, defined as the need for mechanical ventilation for <72 h of life. Secondary outcomes were risk factors associated with NIV failure and complication rates. Results: The study included 173 preterm infants with a median GA of 28 (IQR 27-30) weeks and a median birth weight of 1,100 (IQR 800-1,333) g. The incidence of NIV failure was 15.6%. In the multivariate analysis, lower GA (OR, 0.728; 95% CI, 0.576-0.920) independently increased the risk of NIV failure. Compared to NIV success, NIV failure was associated with higher rates of unfavorable outcomes, including pneumothorax, intraventricular hemorrhage, periventricular leukomalacia, pulmonary hemorrhage, and a combined outcome of moderate-to-severe bronchopulmonary dysplasia or death. Conclusion: NIV failure occurred in 15.6% of the preterm neonates and was associated with adverse outcomes. The use of LISA and newer NIV modalities most likely accounts for the reduced failure rate. Gestational age remains the best predictor of NIV failure and is more reliable than the fraction of inspired oxygen during the first hour of life.

The Ability of the Yeast Wickerhamomyces anomalus to Hydrolyze Immunogenic Wheat Gliadin Proteins.

Gliadins proteins make up around 30% of total wheat flour proteins. They are involved in many immune disorders affecting an increasing number of people who eat foods made with wheat flour. The triggering factor is the accumulation in the gut of immunogenic peptides derived from incomplete degradation of gliadins by gastric proteases. Previous research has revealed the effectiveness of sourdough-fermentation technology or related lactic acid bacteria in reducing wheat flour allergenic proteins. However, there are no single yeast cultures for producing reduced allergenicity wheat products. This study evaluated sourdough-related yeast Wickerhamomyces anomalus strains for their ability to hydrolyze gliadin proteins. All yeast strains were able to degrade gliadins and use them as carbon and nitrogen sources. The proliferation of the yeast strains depended on the gliadin addition; complete hydrolysis was observed after 24 h. The strain showing higher proteolytic activity fermented, acceptably wheat flour dough. The gliadin content of the leavened dough was reduced by 50%. Bread made from the W. anomalus-fermented dough showed a 78% reduction in immunogenic α-gliadins. 50% of the decrease was attributed to the proteolytic activity of the yeast cells, and the other 35% to the baking process. These results show the potential of the yeast W. anomalus as a starter for reducing immunogenicity wheat products.

Brain Gene Silencing with Cationic Amino-Capped Poly(ethylene glycol) Polyplexes.

Therapeutic gene silencing in the brain is usually achieved using highly invasive intracranial administration methods and/or comparatively toxic vectors. In this work, we use a relatively biocompatible vector: poly(ethylene glycol) star-shaped polymer capped with amine groups (4APPA) via the nose to brain route. 4APPA complexes anti- itchy E3 ubiquitin protein ligase (anti-ITCH) siRNA to form positively charged (zeta potential +15 ± 5 mV) 150 nm nanoparticles. The siRNA-4APPA polyplexes demonstrated low cellular toxicity (IC50 = 13.92 ± 6 mg mL-1) in the A431 cell line and were three orders of magnitude less toxic than Lipofectamine 2000 (IC50 = 0.033 ± 0.04 mg mL-1) in this cell line. Cell association and uptake of fluorescently labelled siRNA bound to siRNA-4APPA nanoparticles was demonstrated using fluorescent activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM), respectively. Gene silencing of the ITCH gene was observed in vitro in the A431 cell line (65% down regulation when compared to the use of anti-ITCH siRNA alone). On intranasal dosing with fluorescently labelled siRNA-4APPA polyplexes, fluorescence was seen in the cells of the olfactory bulb, cerebral cortex and mid-brain regions. Finally, down regulation of ITCH was seen in the brain cells (54 ± 13% ITCH remaining compared to untreated controls) in a healthy rat model, following intranasal dosing of siRNA-4APPA nanoparticles (0.15 mg kg-1 siRNA twice daily for 3 days). Gene silencing in the brain may be achieved by intranasal administration of siRNA- poly(ethylene glycol) based polyplexes.

Dynamic regulation of myofibroblast phenotype in cellular senescence.

Cellular senescence is an antiproliferative response with a critical role in the control of cellular balance in diverse physiological and pathological settings. Here, we set to study the impact of senescence on the regulation of cell plasticity, focusing on the regulation of the myofibroblastic phenotype in primary fibroblasts. Myofibroblasts are contractile, highly fibrogenic cells with key roles in wound healing and fibrosis. Using cellular models of fibroblast senescence, we find a consistent loss of myofibroblastic markers and functional features upon senescence implementation. This phenotype can be transmitted in a paracrine manner, most likely through soluble secreted factors. A dynamic transcriptomic analysis during paracrine senescence confirmed the non-cell-autonomous transmission of this phenotype. Moreover, gene expression data combined with pharmacological and genetic manipulations of the major SASP signaling pathways suggest that the changes in myofibroblast phenotype are mainly mediated by the Notch/TGF-ß axis, involving a dynamic switch in the TGF-ß pathway. Our results reveal a novel link between senescence and myofibroblastic differentiation with potential implications in the physiological and pathological functions of myofibroblasts.

Cassava and banana starch modified with maleic anhydride-poly (ethylene glycol) methyl ether (Ma-mPEG): A comparative study of their physicochemical properties as coatings.

This study proposes a simple route to obtain starch grafted copolymers from cassava and banana starches chemically modified with amphiphilic maleic anhydride-poly (ethylene glycol) methyl ether (Ma-mPEG). The starches were extracted from cassava (StC) and banana (StB) pulp and characterized by FTIR spectroscopy, amylose content, scanning electron microscope (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and average molecular weight. Starches were chemically modified with amphiphilic Ma-mPEG in three mass ratios 1:1, 1:2 and 1:3. Thermal behavior and interactions of Ma-mPEG/starch in the St-g-(Ma-mPEG) copolymers were studied by DSC and TGA. The Tg values showed a higher plasticizer effect in the copolymers obtained from StC. Films were formed from StC-g-(Ma-mPEG) and StB-g-(Ma-mPEG) copolymers, thermal and morphological properties were studied. An increase in the mass ratios of Ma-mPEG and the absence of the glycerol in the formulations formed homogeneous films. StC-g-(Ma-mPEG) 1:3 with 2% concentration showed a potential use as coating in strawberries, presenting a lower weight loss (15.5 ± 5.7%) than the control sample (18.6 ± 3.3%).

Evaluation of the physicochemical properties of pectin extracted from Musa paradisiaca banana peels at different pH conditions in the formation of nanoparticles.

Colombia is one of the major producers and exporters of banana Musa paradisiaca. Its consumption is high then its agro-industrial wastes are important source to extract pectin. In the present study, inorganic acids (nitric acid and hydrochloride acid) and organic acids (citric acid and acetic acid) were evaluated to extract pectin from banana peels at pH 2 and 3, through acid hydrolysis during 1h at the temperature of 85 °C. The extraction yield, degree of esterification (DE) and intrinsic viscosity of the pectin were characterized. Nitric acid (NA) allowed to obtain higher extraction yield (54 ± 10%) and citric acid (CA) allowed to obtain higher DE (76.7 ± 2%). Additionally, the effect of polymer concentration and degree esterification, low degree of esterification (LDE, 33.1%) and high degree of esterification (HDE, 76.7%) were evaluated in the pectin nanoparticles formation. The pectin with HDE formed stable nanoparticles with a particle size of 255 ± 11 nm and the zeta potential value of -45 ± 3 mV, independently of the polymer concentration. Morphology analysis showed aggregated of the pectin nanoparticles.

Polyelectrolyte Nanoparticles of Amphiphilic Chitosan/Pectin from Banana Peel as Potential Carrier System of Hydrophobic Molecules.

In this study, pectins were extracted from banana wastes Musa paradisiaca under different acidic conditions, obtaining pectins with different degrees of esterification (DE) depending on the acid type and pH. The formation of the polyelectrolyte nanoparticles was evaluated according to the DE of the pectin, the mass ratio of the polymers of pectin to amphiphilic chitosan (AmCh), and their concentration. The properties of the polyelectrolyte nanoparticles were evaluated at different pH and temperatures. The pectin with 24.3% DE formed polyelectrolyte nanoparticles through the electrostatic interaction with AmCh, which was evidenced by changes in the zeta potential and particle size. The study of mass ratio AmCh:Pectin, to get a stable system, showed that it must be at least equal (1:1), or AmCh must be in higher proportion (6:1, 50:1, 100:1), and the polymers concentration must be 1 mg/mL. The study of the temperature effect showed that, when the temperature increases, the particle size decreases, and the pH study showed a stable particle size for the polyelectrolyte nanoparticles in the range of pH 5-6. Nile Red (NR), a hydrophobic molecule, was encapsulated in the polyelectrolyte nanoparticles with a loading capacity of 1.8% and an encapsulation efficiency of 80%.

Mastocytosis and the Fig Wasp (Blastophaga psenes).

BACKGROUND: Mastocytosis involves the abnormal proliferation of mast cells and clinical variability. In the case of anaphylaxis, the triggering antigen, often associated with Hymenoptera allergens, must be identified. The common fig (Ficus carica) requires the fig wasp (Blastophaga psenes) for pollination. OBJECTIVE: We evaluated the ingestion of B. psenes as a trigger of anaphylaxis in patients with mastocytosis. MATERIAL AND METHODS: Skin prick tests (SPTs) and specific immunoglobulin E to the possible involved allergens were carried out in the patient and in 4 controls allergic to Hymenoptera and fig. Given the possibility of hidden allergens, we studied the source (figs of various origins) and possible hypersensitivity to Hymenoptera allergens, including the fig wasp (B. psenes). RESULTS: In all subjects, the SPT resulted in a wheal (larger than with histamine) with the extract of the inferior part of the female fig but not with the male extract (lower pole and stem). Immune detection was made with the stem and inferior part of figs and venom of Polistes and Vespula. Recognition bands were observed at 25 kDa with female fig extracts that were also recognized by the patient with anaphylaxis to Hymenoptera venom. CONCLUSIONS: We cannot exclude the possibility that the ingestion of fig with Blastophaga antigens may have triggered anaphylaxis in our patient.

Estado vacunal y motivos de no vacunación contra el virus del papiloma humano en adolescentes admitidas en el Hospital Pediátrico del Centro Hospitalario Pereira Rossell / Vaccination status and reasons for non-vaccination against human papillomavirus (HPV) in adolescents admitted at the Pereira Rossell Hospital Center Pediatrics Hospital / Estado vacinal e motivos de não vacinação contra o vírus papiloma humano em adolescentes admitidas no Hospital Pediátrico do Centro Hospitalario Pereira Rossell

Introducción: en Uruguay se ofrece gratuitamente una vacuna tetravalente contra el virus del papiloma humano (VPH) a todas las adolescentes de 12 años o mayores. Las coberturas logradas no han sido las esperadas. Objetivo: describir el estado vacunal contra el VPH, motivos de no vacunación y reporte de efectos adversos en las adolescentes hospitalizadas en un centro de referencia en Uruguay. Material y método: estudio descriptivo mediante encuesta anónima a adolescentes de 12 años o mayores hospitalizadas en cuidados moderados del Hospital Pediátrico del Centro Hospitalario Pereira Rossell durante el segundo semestre de 2016. Se excluyeron las adolescentes que se negaron a participar, las portadoras de retardo mental o pasibles de cuidados paliativos. Se analizó: edad, estado vacunal contra VPH, motivos de no vacunación y de rechazo a la vacuna, efectos adversos. Fue aprobado por el Comité de Ética de la institución. Resultados: se encuestaron 112 adolescentes. Edad media: 13,5 años (12-14,6). Reportaron recibir al menos una dosis de la vacuna contra VPH: 45/112 (40,1%). Motivo de no vacunación más frecuente reportado: desconocimiento de la existencia de la vacuna: 48/67 (71,6%), seguido de rechazo o negativa de la adolescente o adulto responsable: 13/67 (19,4%). El principal motivo de rechazo a recibir la vacuna fue la falta de información: 7/13. No se registraron efectos adversos graves. Conclusiones: se observó una cobertura vacunal similar a datos nacionales. El conocimiento y la información de las adolescentes y sus cuidadores sobre esta vacuna fueron los principales motivos de no vacunación detectados.

Introduction: Uruguay offers a free HPV quadrivalent vaccine to adolescents 12 years of age or older. However, the vaccination rate was not as expected. Objective: to describe the human papillomavirus (HPV) vaccination status, the reasons for non-vaccination and to report adverse effects in hospitalized adolescents in a reference center in Uruguay. Materials and methods: descriptive study by means of an anonymous survey of adolescents of 12 years of age or older hospitalized in moderate care at Pereira Rossell Hospital Center during the second half of 2016. Adolescents who refused to participate were excluded from the study, as well as those with mental retardation and / or subject to palliative care. We analyzed: age, vaccination status against HPV, reasons for non-vaccination and vaccine hesitancy, and adverse effects. The research conducted was approved by the institution's ethics committee. Results: the survey was answered by 112 adolescents who met the inclusion criteria. Mean age was 13.5 years old (12-14.6). 45/112 (40.1%). Adolescents reported having received at least one dose of the HPV vaccine. The most frequent reason for non-vaccination was: lack of knowledge of the vaccine in 48 out of 67 (71.6%), followed by rejection or rejection by the adolescent or responsible adult in 13 out of 67 (19.4%). The main reason for refusal to receive the vaccine reported was: lack of information (7/13). No serious adverse events were reported. Conclusions: vaccination coverage found was similar to national data. Knowledge and information of adolescents and their caregivers about this vaccine were the main reasons detected for non-vaccination.

Introdução: no Uruguai una vacina tetravalente contra o Vírus do Papiloma Humano (VPH) é oferecida gratuitamente a todas as adolescentes com 12 ou mais anos. A cobertura obtida não foi a esperada. Objetivo: descrever o estado vacinal contra o VPH, motivos de não vacinação e informação sobre efeitos adversos nas adolescentes hospitalizadas em um centro de referencia no Uruguai. Materiais e métodos: estudo descritivo, realizado com questionário anônimo respondido por adolescentes com 12 ou mais anos, internadas em cuidados intermediários do Hospital Pediátrico do Centro Hospitalario Pereira Rossell, durante o segundo semestre de 2016. Foram excluídas as adolescentes que não quiseram participar, as portadoras de deficiência mental e/ou passiveis de cuidados paliativos. As seguintes variáveis foram analisadas: idade, estado vacinal contra VPH, motivos de não vacinação e de rejeição à vacina e efeitos adversos. O estudo foi aprovado pelo comité de ética da instituição. Resultados: participaram 112 adolescentes com idade média 13,5 anos (12-14,6). 45 informaram ter recebido pelo menos uma dose da vacina contra VPH (45/112 - 40,1%). O motivo de não vacinação mais frequente foi o desconhecimento da existência da vacina 48/67 (71,6%), seguido de rejeição ou negativa da adolescente ou do adulto responsável 13/67 (19,4%). O motivo principal de rejeição a ser vacinada foi a falta de informação 7/13. Não foram registrados efeitos adversos graves. Conclusões: a cobertura vacinal registrada foi similar aos dados nacionais. O conhecimento e a informação das adolescentes e de seus cuidadores sobre esta vacina foram os principais motivos de não vacinação detectados.

Incidencia del síndrome de abstinencia en niños críticamente enfermos / Incidence of withdrawal syndrome in critically ill children

Objetivo: determinar la incidencia del síndrome de abstinencia (SA), describir presentación clínica e identificar la presencia de factores de riesgo. Metodología: se realizó un estudio prospectivo, observacional, de evaluaciones reiteradas usando la Sophia Observation Withdrawal Symptoms Scale (SOWS), en la Unidad de Cuidado Intensivo de Niños (UCIN) de 20 camas, del Centro Hospitalario Pereira Rossell (CHPR). Se incluyeron los niños ingresados en UCIN entre el 1 de noviembre de 2013 y el 30 de setiembre de 2014 tratados con benzodiacepinas y/o opiáceos por cinco días o más. Se registró: duración de la estadía, fármacos utilizados para sedación y analgesia, días de uso, máximo de dosis, dosis total acumulada. El diagnóstico de SA se realizó a través del uso de la SOWS. Los pacientes fueron divididos en dos grupos, con y sin SA. Se analizaron y compararon las características de ambos grupos. Resultados: se incluyeron 39 niños. La incidencia de SA fue 18% (7/39). Los ítems del SOWS más frecuentes fueron ansiedad y sueño menor a 1 hora. Los niños que desarrollaron SA presentaron dosis acumulativas más elevadas tanto de midazolam (54,1 mg/kg vs 44,2 mg/kg) como de fentanilo (464,2 mg/kg vs 380,1 mg/kg). Conclusiones: el SA fue frecuente en este grupo de niños. Las dosis acumulativas fueron mayores en el grupo con SA. La SOWS es una herramienta útil y de fácil aplicación para el diagnóstico de SA.

Objective: The study aims to determine the incidence of withdrawal syndrome, its clinical features and the presence of risk factors. Methodology: An observational and prospective study. Assessment was repeated and the Sophia Observation Withdrawal Symptoms Scale (SOWS) was used. The study was conducted at the Pediatric Intensive Care Unit (PICU) of Centro Hospitalario Pereira Rossell (CHPR). Hospitalized children in PICU between 1/11/2013- 30/9/2014 and treated with benzodiazepines and opioids during 5 days or more were included in the study. Days of stay at the PICU, agents used for sedation (dose, duration) and cumulative doses were recorded. Withdrawal syndrome diagnosis was done using the SOWS. Results: 39 children were included in the study. The incidence of withdrawal syndrome was 18% (7/39). Children who developed withdrawal syndrome presented higher cumulative doses of midazolam (54.1 mg/kg vs. 44.2 mg/kg) and fentanyl (464.2µg/kg vs. 380.1 µg/kg) than those without withdrawal syndrome. Conclusions: the withdrawal syndrome was frequent in this population. Cumulative doses of midazolam and fentanyl were higher in those with withdrawal symptoms. The SOWS is a useful resource for diagnosis.