Impact of heterozygous ALK1 mutations on the transcriptomic response to BMP9 and BMP10 in endothelial cells from hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension donors.

Heterozygous activin receptor-like kinase 1 (ALK1) mutations are associated with two vascular diseases: hereditary hemorrhagic telangiectasia (HHT) and more rarely pulmonary arterial hypertension (PAH). Here, we aimed to understand the impact of ALK1 mutations on BMP9 and BMP10 transcriptomic responses in endothelial cells. Endothelial colony-forming cells (ECFCs) and microvascular endothelial cells (HMVECs) carrying loss of function ALK1 mutations were isolated from newborn HHT and adult PAH donors, respectively. RNA-sequencing was performed on each type of cells compared to controls following an 18 h stimulation with BMP9 or BMP10. In control ECFCs, BMP9 and BMP10 stimulations induced similar transcriptomic responses with around 800 differentially expressed genes (DEGs). ALK1-mutated ECFCs unexpectedly revealed highly similar transcriptomic profiles to controls, both at the baseline and upon stimulation, and normal activation of Smad1/5 that could not be explained by a compensation in cell-surface ALK1 level. Conversely, PAH HMVECs revealed strong transcriptional dysregulations compared to controls with > 1200 DEGs at the baseline. Consequently, because our study involved two variables, ALK1 genotype and BMP stimulation, we performed two-factor differential expression analysis and identified 44 BMP9-dysregulated genes in mutated HMVECs, but none in ECFCs. Yet, the impaired regulation of at least one hit, namely lunatic fringe (LFNG), was validated by RT-qPCR in three different ALK1-mutated endothelial models. In conclusion, ALK1 heterozygosity only modified the BMP9/BMP10 regulation of few genes, including LFNG involved in NOTCH signaling. Future studies will uncover whether dysregulations in such hits are enough to promote HHT/PAH pathogenesis, making them potential therapeutic targets, or if second hits are necessary.

Dynamics of Nanosecond Laser Pulse Propagation and of Associated Instabilities in a Magnetized Underdense Plasma.

The propagation and energy coupling of intense laser beams in plasmas are critical issues in inertial confinement fusion. Applying magnetic fields to such a setup has been shown to enhance fuel confinement and heating. Here we report on experimental measurements demonstrating improved transmission and increased smoothing of a high-power laser beam propagating in a magnetized underdense plasma. We also measure enhanced backscattering, which our kinetic simulations show is due to magnetic confinement of hot electrons, thus leading to reduced target preheating.

Michael addition of carbonyl compounds to nitroolefins under the catalysis of new pyrrolidine-based bifunctional organocatalysts.

Novel bifunctional pyrrolidine-based organocatalysts for the asymmetric Michael addition of carbonyl compounds to nitroolefins have been synthesised from homoallylamines, which are easily obtained from (R)-glyceraldehyde as a chiral precursor. Under optimal reaction conditions, these bifunctional organocatalysts showed a high catalytic efficiency (almost quantitative yield in most cases) and stereoselectivity in the Michael addition reactions of a variety of aldehydes (up to 98 : 2 dr and 97% ee) and ketones (up to 98 : 2 dr and 99% ee) to nitroolefins.

Carcinoma de los ductos colectores de bellini: presentación de un caso clínico y revisión del diagnóstico diferencial / Collecting (bellini) duct carcinoma: a case presentation

Collecting (Bellini) duct carcinoma (CDC) is a rare and very aggressive variant of renal cell carcinoma. Objectives: To describe the radiological findings of a CDC case and to determine its differential diagnosis. Basic procedures: Review the published works regarding this tumor and compare the radiological findings of our case with those of other described cases. Most important findings: CDCs are well-defined tumors with a high hemorrhagic component, limited internal enhancement and nodal metastases. In the differential diagnosis, if the lesion presents an exophytic growth it should include papillary carcinoma, mainly the sarcomatoid variant and the complex benign lesions (complex cysts or hydatids). However, if the lesion combines an infiltrating pattern, other lesions such as medullary carcinoma or lymphoma will be taken into account. Main conclusions: In the presence of solid-cystic hypovascular lesions and regional lymphadenopathy, CDC must be included in the differential diagnosis.

El carcinoma de las células colectoras de Bellini (CCB), es una variante rara y muy agresiva del carcinoma de células renales. Objetivos: Describir los hallazgos radiológicos de un caso de CCB y determinar su diagnóstico diferencial. Procedimientos básicos: Revisión de los trabajos publicados sobre este tumor y comparar los hallazgos radiológicos de nuestro caso con los de otros casos descritos. Hallazgos más importantes: Los CCB son tumores bien delimitados con alto componente hemorrágico, escaso realce interno y metástasis ganglionares. En el diagnóstico diferencial si la lesión presenta un crecimiento exofítico debería incluirse el carcinoma papilar, fundamentalmente la variante sarcomatoide y las lesiones benignas complejas (quistes complejos o hidatídicos). En cambio, si la lesión asocia un patrón infiltrante se tendrán en cuenta otras lesiones como el carcinoma medular o el linfoma. Conclusiones principales: En presencia de lesiones sólido-quísticas hipovasculares y adenopatías regionales debe incluirse el CCB en el diagnóstico diferencial.

Signatures of the Self-Similar Regime of Strongly Coupled Stimulated Brillouin Scattering for Efficient Short Laser Pulse Amplification.

Plasma-based laser amplification is considered as a possible way to overcome the technological limits of present day laser systems and achieve exawatt laser pulses. Efficient amplification of a picosecond laser pulse by stimulated Brillouin scattering (SBS) of a pump pulse in a plasma requires to reach the self-similar regime of the strongly coupled (SC) SBS. In this Letter, we report on the first observation of the signatures of the transition from linear to self-similar regimes of SC-SBS, so far only predicted by theory and simulations. With a new fully head-on collision geometry, subpicosecond pulses are amplified by a factor of 5 with energy transfers of few tens of mJ. We observe pulse shortening, frequency spectrum broadening, and down-shifting for increasing gain, signatures of SC-SBS amplification entering the self-similar regime. This is also confirmed by the power law dependence of the gain on the amplification length: doubling the interaction length increases the gain by a factor 1.4. Pump backward Raman scattering (BRS) on SC-SBS amplification has been measured for the first time, showing a strong decrease of the BRS amplitude and frequency bandwidth when SBS seed amplification occurs.

Estudio clínico y epidemiológico de la bronquiolitis aguda en pacientes menores de un ano de edad / Clinical and epidemiological study of acute bronchiolitis in patients less than one year of age

Objetivo. Analizar los datos epidemiológicos, etiológicos, clínicos y analíticos de la bronquiolitis aguda en menores de un año de edad. Material y métodos. Estudio retrospectivo de los casos de bronquiolitis diagnosticados durante los meses de diciembre de 2001 y enero de 2002 en el Servicio de Urgencias de nuestro centro. Se obtienen datos epidemiológicos (edad, sexo, factores predisponentes), etiológicos (estudio virológico del moco nasofaríngeo mediante inmunofluorescencia, inmunocromatografía y cultivo), clínicos (presentación y complicaciones) y analíticos (hemograrna, bioquímica y equilibrio ácido-básico). Resultados. Se diagnostican 229 casos de bronquiolitis (59 por ciento niños). De éstos, un 75 por ciento es dado de alta tras valoración en urgencias, un 17 por ciento ingresa en la Sala de Hospitalización y un 8 por ciento ingresan en la Unidad de Cuidados Intensivos Pediátricos (UCIP). Siete pacientes requirieron ventilación mecánica. Los pacientes de entre 4 y 8 meses de edad fueron los más frecuentemente afectados (42 por ciento), si bien fueron los menores de 4 meses los que presentaron una mayor tasa de ingreso. Se identifica virus respiratorio sincitial en un 67 por ciento de los casos. En el 15 por ciento de los mayores de 8 meses, se aísla el virus de la gripe. Los pacientes que requirieron UCIP presentaron más frecuentemente apneas, taquicardia, cianosis, acidosis y niveles de proteína C reactiva (PCR) elevada. Dos pacientes con factores de riesgo tuvieron complicaciones graves: una insuficiencia cardiaca congestiva y un fallo multiorgánico con resultados de exitus. Conclusiones. Aparte del VRS, otros muchos virus pueden producir bronquioliti aguda, especialmente el virus de la gripe. Aunque suele ser leve, en pacientes con factores de riesgo puede presentar gravedad (AU)

Epidemiología de los accidentes en la infancia: estudio prospectivo de 132 casos ingresados en una UCI pediátrica / Epidemiologic assessment of childhood accidents: a prospective study of 132 patients treated in a pediatric intensive care unit

Objetivos: Conocer las causas de los accidentes en la edad pediátrica, su distribución por edades, lugar y tiempo en que se producen, el tipo de lesiones y la mortalidad. Métodos: Se incluyen los pacientes con edad inferior a los 17 años, ingresados correlativamente en un periodo de 18 meses en la UCI pediátrica del Hospital de Sant Pau de Barcelona como consecuencia de un accidente. Resultados: El número total de pacientes fue de 132. Las causas más numerosas fueron los traumatismos (93,18 por ciento), de los cuales el 69,10 por ciento fue consecuencia de accidentes de tráfico, destacando los de motocicleta en un 39,99 por ciento de las ocasiones. El mayor número correspondió a los niños de entre 7 y 14 años (37,87 por ciento). El traumatismo craneoencefálico (TCE) puro o asociado a politraumatismo fue la entidad predominante (80,48 por ciento) y la mortalidad global fue del 8,33 por ciento. El 23,48 por ciento requirió cirugía. El día de mayor siniestralidad fue el domingo (18,18 por ciento) entre las 16 y las 20 horas (36,36 por ciento). El 88,63 por ciento ingresó procedente de otro hospital, el 72,63 por ciento de ellos fue transferido en UCI móvil del Sistema de Emergencias Médicas y el 27,37 por ciento restante en helicóptero del equipo de transporte pe-diátrico del propio hospital. Conclusiones: La principal enfermedad derivada de los accidentes en la edad pediátrica son los traumatismos, en especial los relacionados con los accidentes de tráfico. La edad más frecuente es entre los 7 y 14 años, y el TCE es la entidad más habitual. El día en que más accidentes se registran es el domingo y la hora más común entre las 16 y las 20 horas (AU)

Influence of scale-up on the quality of recombinant human growth hormone.

The aerobic fed-batch production of recombinant human growth hormone (rhGH) by Escherichia coli was studied. The goal was to determine the production and protein degradation pattern of this product during fed-batch cultivation and to what extent scale differences depend on the presence of a fed-batch glucose feed zone. Results of laboratory bench-scale, scale-down (SDR), and industrial pilot-scale (3-m(3)) reactor production were compared. In addition to the parameters of product yield and quality, also cell yield, respiration, overflow, mixed acid fermentation, glucose concentration, and cell lysis were studied and compared. The results show that oxygen limitation following glucose overflow was the critical parameter and not the glucose overflow itself. This was verified by the pattern of byproduct formation where formate was the dominating factor and not acetic acid. A correlation between the accumulation of formate, the degree of heterogeneity, and cell lysis was also visualized when recombinant protein was expressed. The production pattern could be mimicked in the SDR reactor for all parameters, except for product quantity and quality, where 30% fewer rhGH-degraded forms were present and where about 80% higher total yield was achieved, resulting in 10% greater accumulation of properly formed rhGH monomer.

[Myocardial perforation secondary to central venous catheterization]. / Perforación miocárdica secundaria a cateterización venosa central.

Authors present miocardiac perforation in two children 41 and 20 days old respectively, in whom a central venous catheter by phlebotomy for administration of fluids and parenteral nutrition was introduced: the end of the catheter was left at the level of right auricule. In the first case the perforation presented two hours after introducing the catheter, and in the second case, perforation was later. In neither case were there clinical signs of cardiac tamponade, and an unexpected heart respiratory arrest occurred which was reanimated by a pericardial punction. In the second case perforation was discovered by means of necroscopic study.