Biochar production from cellulose under reductant atmosphere: influence of the total pyrolysis time.

Today's rising energy costs, coupled with increasing energy demand, make it necessary to search for more efficient energy processes. In recent years, there have been increasing efforts to develop efficient catalysts based on waste-derived char, by a single step where the carbon precursor and the metallic active phase one undergo a single common thermal process under a reductant atmosphere at high temperature. The use of a reductant atmosphere drives the formation of carbonaceous materials with different characteristics than those obtained under the standard nitrogen-inert one. Our work evaluates the influence of the residence time and the heating rate on the physicochemical properties of the biochar obtained. Relatively long residence times and slow heating rates, improve the yield to the resulting biochar, without increasing production cost, making the subsequent char-based metallic catalyst synthesis more efficient. The heating rate was shown to be key in improving the properties of the char in a smoother and more controlled way, unlocking a new working pathway for the efficient design and production of char-based catalysts in a one-pot synthesis.

Hemorragia masiva tras fístula arterio-esofágica por una arteria subclavia aberrante desconocida / Massive hemorrhage after arterioesophageal fistula from an unknown aberrant subclavian artery

La arteria subclavia derecha aberrante tiene una incidencia de un 0,5-1% en la población, con una localización generalmente retroesofágica. Puede llevar a la formación de una fístula arterio-esofágica en pacientes con factores de riesgo predisponentes por dispositivos colocados en posición esofágica o traqueal, al ser particularmente susceptible a la compresión extrínseca y a la necrosis por presión.Presentamos el caso de un paciente con una fístula traqueo-esofágica posquirúrgica, que desarrolló un sangrado masivo por una fístula arterio-esofágica secundaria a una arteria subclavia derecha aberrante desconocida. Para el manejo hemostático se realizaron maniobras alternativas, como la colocación de una sonda urinaria tipo Foley en el punto de sangrado y la posterior colocación de un balón de Sengstaken-Blakemore en posición craneal.Dada la gravedad del cuadro y el posible retraso diagnóstico, parece adecuado considerar la realización de un angio-TC preoperatorio en pacientes con factores de riesgo sometidos a estos procedimientos.(AU)

The aberrant right subclavian artery has an incidence of 0.5-1% in the population, generally with retroesophageal location. It can lead to the formation of an arterio-esophageal fistula in patients with predisposing risk factors due to devices placed in esophageal or tracheal position, as it is particularly susceptible to extrinsic compression and pressure necrosis.We present the case of a patient with a postsurgical tracheoesophageal fistula, who developed massive bleeding due to an arterioesophageal fistula secondary to an unknown aberrant right subclavian artery. For hemostatic management, alternative maneuvers were performed, such as the placement of a Foley-type urinary catheter at the point of bleeding and the subsequent placement of a Sengstaken-Blakemore balloon in cranial position.Given the severity of the condition and the possible diagnostic delay, it seems appropriate to consider performing a preoperative CT angiography in patients with risk factors who undergo these procedures.(AU)

Massive hemorrhage after arterioesophageal fistula from an unknown aberrant subclavian artery.

The aberrant right subclavian artery has an incidence of 0.5%-1% in the population, generally with retroesophageal location. It can lead to the formation of an arterio-esophageal fistula in patients with predisposing risk factors due to devices placed in esophageal or tracheal position, as it is particularly susceptible to extrinsic compression and pressure necrosis. We present the case of a patient with a postsurgical tracheoesophageal fistula, who developed massive bleeding due to an arterioesophageal fistula secondary to an unknown aberrant right subclavian artery. For hemostatic management, alternative maneuvers were performed, such as the placement of a Foley-type urinary catheter at the point of bleeding and the subsequent placement of a Sengstaken-Blakemore balloon in cranial position. Given the severity of the condition and the possible diagnostic delay, it seems appropriate to consider performing a preoperative CT angiography in patients with risk factors who undergo these procedures.

Testing an Adapted Auditory Verbal Learning Test Paradigm for fMRI to Lateralize Verbal Memory in Patients with Epilepsy.

BACKGROUND AND PURPOSE: fMRI is a noninvasive tool for predicting postsurgical deficits in candidates with pharmacoresistant temporal lobe epilepsy. We aimed to test an adapted paradigm of the Rey Auditory Verbal Learning Test to evaluate differences in memory laterality indexes between patients and healthy controls and its association with neuropsychological scores. MATERIALS AND METHODS: We performed a prospective study of 50 patients with temporal lobe epilepsy and 22 healthy controls. Participants underwent a block design language and memory fMRI. Laterality indexes and the hippocampal anterior-posterior index were calculated. Language and memory lateralization was organized into typical and atypical on the basis of laterality indexes. A neuropsychological assessment was performed with a median time from fMRI of 8 months and was compared with fMRI performance. RESULTS: We studied 40 patients with left temporal lobe epilepsy and 10 with right temporal lobe epilepsy. Typical language occurred in 65.3% of patients and 90.9% of healthy controls (P = .04). The memory fMRI laterality index was obtained in all healthy controls and 92% of patients. The verbal memory laterality index was bilateral (24.3%) more frequently than the language laterality index (7.69%) in patients with left temporal lobe epilepsy. Atypical verbal memory was greater in patients with left temporal lobe epilepsy (56.8%) than in healthy controls (36.4%), and the proportion of bilateral laterality indexes (53.3%) was larger than right laterality indexes (46.7%). Atypical verbal memory might be associated with higher cognitive scores in patients. No relevant differences were seen in the hippocampal anterior-posterior index according to memory impairment. CONCLUSIONS: The adapted Rey Auditory Verbal Learning Test paradigm fMRI might support verbal memory lateralization. Temporal lobe epilepsy laterality influences hippocampal memory laterality indexes. Left temporal lobe epilepsy has shown a higher proportion of atypical verbal memory compared with language, potentially to memory functional reorganization.

Accidente cerebrovascular en una Unidad de Cuidados Intensivos Pediátricos. "11años de ACV en UCIP" / Stroke in a Pediatric Intensive Care Unit. "11 years of stroke in the PICU "

Introducción: La incidencia de ACV (Accidente Cerebrovascular) en niños es de 2-13/100.000 niños por año, siendo una de las 10 causas más frecuentes de muerte en la infancia. La misma varía entre 6-40% dependiendo de las series publicadas y de los subtipos de ACV. Existen diferencias importantes entre el ACV en niños y adultos, ya que las características neurológicas y de la hemostasia son muy distintas en cada grupo. En niños deben ser investigados múltiples factores de riesgo que a menudo se superponen entre sí. Materiales y métodos: Trabajo descriptivo retrospectivo por revisión de historias clínicas, de una población de niños con diagnóstico de ACV ingresados en UCIP en un período de 10 años. Resultados: Se confirmó el diagnóstico de ACV en un total de 84 pacientes. El 70,24% de la población correspondía a ACVH (Accidente Cerebrovascular Hemorrágico) y un 29,76% ACVI (Accidente Cerebrovascular Isquémico). El 60,71 % eran masculinos. La mediana del tiempo entre el inicio de los síntomas y el ingreso a UCIP, en ambos grupos fue de 1 día con rango entre 1-17 días para los ACVH y 1-9 para los ACVI. Se evaluaron variables clínicas, de diagnóstico y de tratamiento según ambos tipos de ACV. Conclusión: El ACV requiere de un abordaje multidisciplinario. La realización de neuro-imágenes es un pilar fundamental para el diagnóstico y no debe ser pospuesto. El monitoreo y tratamiento está enfocado en minimizar el daño en el parénquima cerebral circundante (AU)

Introduction: The incidence of stroke in children is 2-13/100,000 children a year, being one of the 10 most common causes of death in childhood. Mortality varies between 6 and 40% depending on the series reported and according to the different subtypes of stroke. There are important differences between childhood and adult stroke, as the neurological features and characteristics of hemostasis vary greatly. In children, multiple risk factors that often overlap should be investigated. Material and methods: A retrospective descriptive review of the clinical records of a series of patients with stroke admitted to the pediatric intensive care unit (PICU) over a period of 10 years was conducted. Results: The diagnosis of stroke was confirmed in 84 patients; 70.24% had hemorrhagic and 29.76% ischemic stroke. Overall, 60.71% were boys. Median time between symptom onset and admission to the PICU was one day in both groups, ranging from 1-17 días for those with hemorrhagic and from 1-9 days for those with ischemic stroke. Clinical, diagnostic, and treatment variables were evaluated for both types of stroke. Conclusion: Stroke requires a multidisciplinary approach. Neuroimaging is essential for the diagnosis and should not be postponed. Monitoring and treatment is focused on minimizing damage to the surrounding brain parenchyma (AU)

Modulation of epileptic networks by transient interictal epileptic activity: A dynamic approach to simultaneous EEG-fMRI.

Epileptic networks, defined as brain regions involved in epileptic brain activity, have been mapped by functional connectivity in simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) recordings. This technique allows to define brain hemodynamic changes, measured by the Blood Oxygen Level Dependent (BOLD) signal, associated to the interictal epileptic discharges (IED), which together with ictal events constitute a signature of epileptic disease. Given the highly time-varying nature of epileptic activity, a dynamic functional connectivity (dFC) analysis of EEG-fMRI data appears particularly suitable, having the potential to identify transitory features of specific connections in epileptic networks. In the present study, we propose a novel method, defined dFC-EEG, that integrates dFC assessed by fMRI with the information recorded by simultaneous scalp EEG, in order to identify the connections characterised by a dynamic profile correlated with the occurrence of IED, forming the dynamic epileptic subnetwork. Ten patients with drug-resistant focal epilepsy were included, with different aetiology and showing a widespread (or multilobar) BOLD activation, defined as involving at least two distinct clusters, located in two different lobes and/or extended to the hemisphere contralateral to the epileptic focus. The epileptic focus was defined from the IED-related BOLD map. Regions involved in the occurrence of interictal epileptic activity; i.e., forming the epileptic network, were identified by a general linear model considering the timecourse of the fMRI-defined focus as main regressor. dFC between these regions was assessed with a sliding-window approach. dFC timecourses were then correlated with the sliding-window variance of the IED signal (VarIED), to identify connections whose dynamics related to the epileptic activity; i.e., the dynamic epileptic subnetwork. As expected, given the very different clinical picture of each individual, the extent of this subnetwork was highly variable across patients, but was but was reduced of at least 30% with respect to the initially identified epileptic network in 9/10 patients. The connections of the dynamic subnetwork were most commonly close to the epileptic focus, as reflected by the laterality index of the subnetwork connections, reported higher than the one within the original epileptic network. Moreover, the correlation between dFC timecourses and VarIED was predominantly positive, suggesting a strengthening of the dynamic subnetwork associated to the occurrence of IED. The integration of dFC and scalp IED offers a more specific description of the epileptic network, identifying connections strongly influenced by IED. These findings could be relevant in the pre-surgical evaluation for the resection or disconnection of the epileptogenic zone and help in reaching a better post-surgical outcome. This would be particularly important for patients characterised by a widespread pathological brain activity which challenges the surgical intervention.

Disease Resistant Bouquet Vine Varieties: Assessment of the Phenolic, Aromatic, and Sensory Potential of Their Wines.

The search for grape varieties resistant to diseases and to climatic changes notably concerns the wine industry. Nine monovarietal wines from new red grape varieties resistant to cryptogamic diseases (downy and powdery mildews) were evaluated in terms of their total phenolic, anthocyanin and proanthocyanidin contents, anthocyanin profile, volatile composition, and sensory attributes. Thus, the question remains, will these hybrid grapes (≥97.5% of Vitisvinifera genome) lead to wines with organoleptic properties similar to those of Vitisvinifera wines that consumers are used to? Total phenolic (1547-3418 mg GA/L), anthocyanin (186-561 mg malvidin/L), and proanthocyanidin (1.4-4.5 g tannins/L) contents were in broad agreement with those previously described in the literature for monovarietal wines produced with well-known red grape varieties (Cabernet Sauvignon, Merlot, Syrah). With regard to fruity aroma, ethyl esters of straight-chain fatty acids (530-929 µg/L) stood out clearly as the major volatile components for all hybrid wines considered. Sensory analysis revealed significant differences (p < 0.05) for visual aspect, aroma, flavor, global balance, astringency, and body. Overall, these new hybrid grape varieties are not only resistant to cryptogamic diseases, but also present enough potential to become quality wines, since their phenolic and volatile attributes are close to those of common red monovarietal wines.

Use of oak wood during malolactic fermentation and ageing: Impact on chardonnay wine character.

Malolactic fermentation (MLF) and oak barrels aging are two oenological processes which modify wine composition and sensory characteristics. The effect of MLF-container (stainless steel tanks, barrels) and barrel toasting (T1, T2, T3) on ellagitannin concentration, volatile composition and sensory attributes of Chardonnay wines was evaluated. Barrel toasting had higher impact on ellagitannin content than MLF-container. When comparing both MLF-modalities, barrel-fermented wines exhibited greater amounts of vanillin and whiskey-lactones but lower concentrations of fruity aroma compounds. Regarding sensory analysis, greater citrus and floral aromas were perceived for MLF-tank wines, and higher nuts aroma for MLF-barrel wines. Using barrels as MLF-containers i) did not change the aroma perception defining Chardonnay character (peach, apricot and gun flint); ii) did not impact the aromatic intensity and persistence, sweetness, acidity, mouthfeel volume and/or bitterness; and iii) did not confer significantly higher overall woody aromas which might mask fruity, floral and mineral (gun flint) character.

Estudio de la frecuencia de parpadeo y evaluación de la película lagrimal en superficie ocular de cobayos / Eye blinking frequency studies and tear film evaluation in guinea pig's ocular surface

OBJETVOS: La Queratopatía Climática Esferoidea (QCE) es una enfermedad degenerativa de la córnea humana caracterizada por la agregación de proteínas bajo el epitelio y una progresiva opacidad corneal, causada por condiciones ambientales desfavorables. Si bien esta patología fue descripta por primera vez hace más de cien años, en la actualidad no existe un modelo experimental de QCE que permita avanzar en el conocimiento de la etiopatogenia de la misma para plantear posibles tratamientos. En el intento por desarrollar este modelo en cobayos y debido a la escasa bibliografía disponible que describa la anatomía, fisiología y superficie ocular de estos animales, realizamos diferentes tests fisiológicos de superficie ocular en cobayos y lo compararemos con el humano. MÉTODOS: Para estos estudios se utilizaron 15 cobayos. Se realizaron videograbaciones de los mismos en un ambiente de tranquilidad y bajo ciertos estímulos para estudiar la dinámica de parpadeo y sueño. Con el fin de analizar la producción y la estabilidad del film lagrimal, se realizaron test de Schirmer, medición de la altura del menisco lagrimal inferior por OCT visante y tiempo de ruptura precorneal (TRP) respectivamente. RESULTADOS: El cobayo parpadea de forma completa y parcial, siendo más frecuente ésta última modalidad. La frecuencia y tipo de parpadeos/ minuto fue: Total= 2.35± 0.87; completos= 0.68±0.43; parciales=1.49±0.75. Su frecuencia de parpadeo es 5 veces menor que en humanos. La respuesta palpebral frente a diferentes estímulos externos fue escasa. Los cobayos no poseen hábitos nocturnos como muchos roedores y duermen por cortos períodos. A menudo no cierran completamente los ojos. Test de Schirmer cobayos: 8.14±1.86 mm/5 min (Humanos: 11.9 ± 6.79 mm/5 min). Altura menisco inferior cobayos: 0,206 ± 0,059 mm (Humanos: 0,277 ± 0,033 mm). TRP cobayos: 2-3 min. (Humanos: 10-15 seg). CONCLUSIONES: Los resultados obtenidos muestran que el cobayo, a diferencia de humanos, tiene una frecuencia de parpadeo menor. A su vez, esto se puede correlacionar con una producción de lágrima disminuida (objetivada con Test de Schirmer) y una mayor estabilidad de la película lagrimal, como lo evidencia el prolongado TRP. (AU)

PURPOSE: Climatic spheroidal keratophaty (CSK), also known as climatic droplet keratopathy (CDK), is a degenerative human corneal disease characterized by protein aggregation under the corneal epithelium that leads to a progressive corneal opacity. Of unknown etiology, it is related to harsh environmental conditions. Although CSK was described many years ago and no experimental model of the disease is still available, we perform different physiological test on the guinea pig´s ocular surface and compare the results with human parameters. METHODS: 15 guinea pigs were used for this study. Video recordings of their behavior in a quiet environment and under certain stimulus were performed to study the blinking and sleeping dynamic. Test de Schirmer, Inferior tear meniscus height measurement, Break up time (BUT) test were performed, with the aim of analyze the tear film production and stability. RESULTS: The guinea pig blinks in both a complete and a partial way, being more frequent the last one. The blink type and frequency were: Total = 2.35± 0.87; complete= 0.68±0.43; partial=1.49±0.75. The blink frequency is 5 times smaller than in humans. The eyelid response against different external stimuli was poor. The night habits of this animals were different compared with other rodents, they sleep for a short periods of time. They often do not close their eyes completely. Schirmer test in guinea pigs was 8.14±1.86 mm/5 min (humans: 11.9 ± 6.79 mm/5 min). Inferior tear meniscus height measurement in guinea pigs was 0,206 ± 0,059 mm (humans: 0,277 ± 0,033 mm). BUT in Guinea Pig: 2-3 min. (Humans: 10-15 seg). CONCLUSIONS: Guinea Pigs have a short blink frequency unlike humans, a decreased tear production, and an increased tear film stability. (AU)

Bevacizumab intravítreo como tratamiento de maculopatías miópicas neovasculares / Intravitreal bevacizumab for neovascular myopic maculopathy

INTRODUCCIÓN: La miopía patológica es una causa importante de pérdida de visión irreversible y es la cuarta a novena causa más frecuente de ceguera en el mundo. Es también conocida como miopía alta, degenerativa o maligna; condición en la que los individuos tienen una longitud axial superior a 25,5 - 26,5mm, y/o un error de refracción de por lo menos -5.0 dioptrías, acompañado por cambios patológicos. La neovascularización coroidea (NVC) asociada a miopía patológica puede resultar en la pérdida significativa de la visión y/o la ceguera. La NVC suele ser subfoveal y es una importante complicación, desarrollándose en aproximadamente 5-10% de ojos con miopía patológica. De manera similar que en otras enfermedades maculares asociadas a NVC, se ha encontrado un aumento del nivel del factor de crecimiento de endotelial (VEGF) en NVC miópicas, y por lo tanto, la terapia anti-VEGF sería útil. Desde la introducción en oftalmología de agentes anti factor de crecimiento de endotelial (anti-VEGF), el tratamiento anti-angiogénico con antiVEGF intravítreo se ha convertido en el tratamiento de primera línea para la NVC miópica. El bevacizumab es un anticuerpo monoclonal humano, anti factor de crecimiento endotelial (anti-VEGF), que inhibe la proliferación de nuevas células endoteliales produciendo un bloqueo de la fosforilación de las uniones estrechas (tight junctions) de las mismas. Este mecanismo produciría una mejoría anatómica-funcional en los pacientes e impediría una de las complicaciones más importantes de esta patología como lo es la neovascularización. OBJETIVO: Evaluar la eficacia de bevacizumab intravítreo (Avastin ®™) como tratamiento de la neovascularización coroidea (NVC) en miopías patológicas. PACIENTES Y MÉTODOS: Se evaluaron retrospectivamente 22 pacientes con diagnóstico de maculopatía miópica neovascular tratados mediante inyección intravítrea de bevacizumab, con un seguimiento mínimo de 12 meses. La agudeza visual se evaluó mediante tabla de Snellen y se convirtió en unidades LogMAR. El espesor macular se evaluó mediante tomografía de coherencia óptica (OCT). Las variables cuantitativas se analizaron mediante medidas de tendencia central, dispersión y forma. Los cambios en la agudeza visual se calcularon utilizando la prueba de Wilcoxon para variables apareadas y con la prueba de Mann Whitney para comparar variables independientes. Las diferencias entre variables continuas con distribución normal y de muestras independientes fueron calculadas mediante la prueba T de Student. RESULTADO: Se estudiaron 22 pacientes con diagnóstico de maculopatía miópica neovascular, cuya edad promedio fue de 59,68 (de 11,75; rango 34,00 ­ 85,00), de los cuales 7 (31,8%) fueron hombres y 15 (68,2%) fueron mujeres. El tiempo de seguimiento fue de 12 meses. El tiempo promedio transcurrido entre el comienzo de los síntomas y el inicio del tratamiento fue 38,68 (de 34,63) días. El 68,2% (15) de los pacientes consultaron por disminución brusca de la agudeza visual del ojo afectado y 31,8% (7) consultaron por metamorfopsias. Todos los pacientes presentaron miopía patológica (> 5.0 dioptrías). La cantidad total de inyecciones durante el seguimiento tuvo una media de 4,27 (DE 1.86; Rango 2,00 ­ 9,00), con un máximo de 9 inyecciones y un mínimo de 2 inyecciones. Durante los primeros 6 meses se realizaron la mayor parte de las inyecciones con una media de 3,36 (DE 1,22; Rango 1,00 ­ 6,00). La mediana de la AV al momento del tratamiento fue de 1,00 (P25-75=0,40-1,00). Al analizar la totalidad de los pacientes se encontró que existe una diferencia significativa al comparar las agudezas visuales previas al tratamiento y a los 12 meses de tratamiento (p=<0.0001). La mejoría franca de la AV se observó entre el primer mes (mediana= 1.00 RIQ= 0,6) y los 3 meses de tratamiento (mediana= 0,60 RIQ= 0,6) (p= 0,0002), mientras que no hubo diferencias significativas en la variación de la AV más allá de los 3 meses de seguimiento (p= 0,09). Al estudiar los espesores maculares antes del tratamiento, encontramos una mediana de 290 (RIQ=105); mientras que a los 12 meses de seguimiento fue de 269,50 (RIQ= 91). Teniendo en cuenta el total de los pacientes estudiados, no hubo diferencias significativas en el análisis del espesor macular medido por OCT antes y después del tratamiento (p=0,8812). CONCLUSIONES: El bevacizumab fue eficaz en el tratamiento de la maculopatía miópica, si bien no se encontraron diferencias significativas en la variación del espesor macular. En nuestra serie no hubo complicaciones oculares ni sistémicas vinculadas al tratamiento. (AU)

BACKGROUND: Pathological myopia is observed in about 2% of the general population. Submacular choroidal neovascularization is a leading cause of severe visual loss and blindness in eyes with pathological myopia, affecting 4-11% of those eyes. PURPOSE: Our aim is to evaluate the efficacy and safety of intravitreal bevacizumab in the treatment of neovascular myopic maculopathy (NMM). PATIENTS AND METHODS: 22 nonpreviously treated eyes of 22 consecutive patients with NMM. were reated with monthly intravitreal injections of bevacizumab and followed up for 12 months. Changes in BCVA and central macular thickness were evaluated at 12 months of follow-up. Snellen best-corrected visual acuity (BCVA) was converted into LogMAR units. Mean central macular thickness was obtained by means of spectral domain optical coherence tomography (SP-OCT). Quantitative variables were analyzed with central tendency, dispersion and shape. Changes in BCVA were calculated with Wilcoxon test in paired variables. Mann Whitney test was used to compare independent variables. Differences between continuous variables with normal distribution and independent samples were calculated with the Student T test. Main outcome measures: Changes in BCVA and central macular thickness at12 months of follow-up. RESULTS: Mean age was 54.45 (SD 12.30; r= 28.00 ­ 79.00); 7 patients (31.8%) were male and 15 (68.2%) female. Mean spherical equivalent refractive error was -10.89±4.13 (r= 7.00 to -21,00) Mean time elapsed between initial symptoms and the beginning of treatment was 38.68 (SD34.63) days. Patients received a mean of 4.27 (SD 1.86; r=2.00 to 9.00) injections. Most injections were performed during the first 6 months of treatment (mean 3.36 months; SD 1.22; r=1.00 to 6.00). Median BCVA at baseline was 1.00 (P25-75=0.40-1.00) and at 12 months 0.45 (P25-75=0.30- 0.70) (p<0.0001). Significant visual improvement was observed between the first (median=1.00, IQR= 0.6) and the third month of treatment (median=0.60, IQR=0.6) (p=0.0002), with no further significant improvement (p=0.09). No ocular or systemic side effects attributable to treatment were observed. When comparing patients 55 years old or younger with those older, and between both genders, all individuals improved, although not significantly (Mann Whitney for age P=0.1765; gender P=3454). No significant improvement in macular thickness was observed (pretreatment median thickness 290 microns, IQR=105; month 12 post-treatment median thickness 269.5 microns, IQR=91) (P=0.8812). CONCLUSIONS: Bevacizumab was effective and safe in our series of myopic patients with neovascular maculopathy, and visual gain remained stable during follow-up. (AU)

Bevacizumab intravítreo en el tratamiento de las oclusiones venosas de la retina / Bevacizumab in the treatment of macular edema complicating retinal vein occlusions

INTRODUCCIÓN: Dentro de las vasculopatías retinianas, las oclusiones venosas de la retina (OVR) representan la segunda causa más frecuente de pérdida de visión luego de la retinopatía diabética. Se han descripto dos tipos diferentes de OVR: la oclusión de vena central de la retina (OVCR), y la oclusión de rama venosa retinal (ORVR). De acuerdo al compromiso oclusivo del lecho capilar de la retina, se las clasifica en isquémicas (o no perfundidas), y no isquémicas (perfundidas), presentando una patogénesis, diagnóstico, pronóstico y tratamiento diferente. Se ha demostrado que los niveles de factor de crecimiento vascular endotelial (VEGF) aumentan significativamente en las oclusiones venosas retinianas, lo que tiene como consecuencia una disfunción de la barrera hematorretinal y el aumento de la permeabilidad vascular, con el consecuente edema macular. La inyección intravítrea de bevacizumab, un anticuerpo monoclonal recombinante que actúa en forma directa contra cualquier forma activa de VEGF, ha demostrado ser efectiva para reducir el espesor macular y mejorar la agudeza visual en el tratamiento de OVR. OBJETIVO: Evaluar los cambios en la agudeza visual y en los espesores maculares de pacientes con oclusiones venosas retinianas tratados con inyecciones intravítreas de bevacizumab. Pacientes y métodos: Se evaluaron retrospectivamente 39 pacientes con diagnóstico de oclusión venosa retiniana (OVR) complicada de edema macular y tratados mediante inyección intravítrea de 1,25 mg/0,05 ml bevacizumab (Avastin®, Roche Diagnostic GmbH, Manheim, Alemania), con un seguimiento mínimo de 18 meses. La agudeza visual se evaluó mediante tabla de Snellen y se convirtió en unidades LogMAR. El espesor macular se evaluó mediante tomografía de coherencia óptica (OCT). Según la presentación clínica se las clasificó en: 1. Oclusión de rama (ORVR), incluyendo las oclusiones hemisféricas y 2. Oclusión de vena central (OVCR), incluyendo oclusión venosa hemicentral. A su vez, mediante angiografía fluoresceínica se las clasificó en oclusiones predominántemente isquémicas, y predominántemente no isquémicas. Las variables cuantitativas se analizaron mediante medidas de tendencia central, dispersión y forma. Los cambios en la agudeza visual se calcularon utilizando la prueba de Wilcoxon. Las diferencias entre variables continuas fueron calculadas mediante la prueba T de Student para variables paramétricas, y Mann Whitney para variables no paramétricas. RESULTADOS: La edad promedio fue de 66,8 años (DE: 13,65; rango= 31-92 años). El 55% de los casos estudiados fueron OVCR y el 37,5% ORVR. La media del total de inyecciones durante los 18 meses de seguimiento fue de 4,11±1,61 (rango= 1 a 6). La terapia con láser de rescate se realizó en 10 (25%) pacientes. Todos los pacientes que debieron ser tratados con láser tuvieron una AV inferior a 1 décima al final del seguimiento. La agudeza visual promedio al inicio del tratamiento fue de 1,092 con una desviación estándar (DE) de 0,36, con un rango de 0,10 y 1,60. Tras el inicio del tratamiento, todos los grupos de pacientes logran un incremento significativo en la AV (P= <0,0001). A los 18 meses de tratamiento la agudeza visual promedio fue de 0,739 con una DE de 0,45 con un rango de entre 0,00 y 1,50. La agudeza visual media de los pacientes con OVCR antes del tratamiento fue de 1,09 (DE: 0,35; rango= máxima 0,50 y mínima 1,60), y a los 18 meses de tratamiento de 0,87 (DE: 0,73; rango= 0,20 a 1,50). En cambio, los pacientes con ORVR antes del tratamiento presentaron una media de 1,10 (DE: 0,31; rango= máxima de 0,40 y mínima de 1,6), y luego del tratamiento una media de 0,53 (DE: 0,38; rango= máxima 0,1 y mínima 1,2). El 54,5% de los casos fue de predominio isquémico o mixtos, y el 43,5% fue a predominio edematosos al inicio del tratamiento. La agudeza visual media de los pacientes con tipo edematoso fue de 0,93 (DE: 0,34; rango= máxima 0,10 y mínima 1,40), mientras que los pacientes con patología isquémica presentaron una media de 1,25 (DE: 0,32; rango= máxima de 0,40 y mínima de 1,6). Ambos grupos respondieron en forma significativa al tratamiento (p< 0.05). Sin embargo, los pacientes con predominio edematoso lograron una mejoría mayor que aquellos con predominio isquémico. (P=0.0054) La agudeza visual media de los pacientes con predominio edematoso a los 18 meses del tratamiento fue de 0,50 (DE: 0,44; rango= máxima 0,0 y mínima 1,40), mientras que los pacientes con predominio isquémico presentaron una media de 0,97 (DE: 0,35; rango= máxima 0,20 y mínima 1,4). La media de los espesores maculares previo al inicio del tratamiento fue de 654.19 ± 272.05 micras (rango= 215 a 1497 micras), mientras que la media luego del tratamiento fue de 449 ± 247,62 micras (rango= 140 a 1005 micras) (p=0,0009). No hubo efectos colaterales ni complicaciones locales ni sistémicas atribuibles a la inyección de bevacizumab durante el seguimiento. CONCLUSIÓN: El bevacizumab fue eficaz en el tratamiento del edema macular secundario a OVR. La respuesta terapéutica fue mayor en las ORVR. En nuestra serie no hubo complicaciones oculares ni sistémicas vinculadas al tratamiento. (AU)

INTRODUCTION: Within the retinal vascular disease,retinal venous occlusion (RVO) represents the second most common cause of vision loss after diabetic retinopathy. In turn, it is estimated that the RVO affects approximately 1.6% of people worldwide. It has been described two different types of RVO: the central retinal vein occlusion (CRVO), which includes the hemicentral retinal vein occlusion (HCRVO), and the branch retinal vein occlusion (BRVO), which includes Major BRVO (occlusion of a retinal vein that drains one of the quadrants or more), Minor BRVO (occlusion of a retinal vein that drains less than a quadrant) and Hemispheric retinal vein occlusions (half or more of the retina). According to the occlusive pattern of the retinal capillary bed, this disease is classified as ischemic (or non perfused); when the areas of noncapillary perfusion, seen under fluorescein angiography, have an extension of more than 10 disc diameters; and non-ischemic (o perfused), presenting a pathogenesis, diagnosis, prognosis and different treatment. Non-ischemic form is generally more benign, with a less dramatic visual impairment, a greater chance of spontaneous recovery, a better treatment response, and generally has no risk of neovascularization. Instead; ischemic form is much more severe, causing a more dramatic visual acuity decline, with little chance of clinical improvement, an increased risk of blindness and an increased risk of neovascularization. Although the physiopathogenesis of OVR is not accurately known, it is suggested that the thickening and stiffness of arteries and arterioles caused by arteriosclerosis leads to compression of the retinal veins at the sites where adventitia is shared with arteries (in its intraneural route to the optic nerve and the arteriovenous crossings), leading eventually to a turbulent blood flow, damage to endothelial cells, thrombus formation and eventual vein occlusion. This theory is supported by studies showing pathological structural changes in veins and arteries of patients with VO. Moreover, other factors related to venous deregulation, such as inadequate vasoconstriction and increased vascular permeability, could also play an important role in the retinal venous occlusive phenomena. In some patients, especially young people and adults under 50 years old, inflammatory disorders and hypercoagulable states may contribute to the hysiopathogenesis of the RVO. It has been shown that the presence of vascular endothelial growth factor (VEGF) increased significantly the chances to develop retinal vein occlusions. The result is a blood­retinal barrier dysfunction and an increased vascular permeability, with consequent macular edema. It has also been reported that VEGF plays an important role in the pathogenesis of macular edema in both ORV and CRVO.10 While there is insufficient level 1 evidence to support OVR treatment, multiple therapeutic possibilities have been described, such as anticoagulation, intravitreal fibrinolysis, hemodilution, laser photocoagulation, laser-induced anastomosis, radial optical neurotomy, adventiciotomía, intravitreal injection of triamcinolone acetonide, intravitreal injection of dexamethasone, and injection intravitreal antiangiogenic monoclonal antibodies, such as ranibizumab, bevacizumab, and aflibercept, alone or associated with photocoagulation, have shown efficacy and variables complications rates. Intravitreal injection of bevacizumab, a recombinant monoclonal antibody that acts directly against any active form of VEGF, has been shown to be effective in reducing macular thickness and improving visual acuity in the treatment of OVR. However, the need for multiple injections has been reported since the effects of intravitreal bevacizumab (as well as the other antiangiogenics) are short-lived. On one hand, Bevacizumab has the disadvantage that it is administered off-label; in addition each dose must be extracted from a vial for oncological use, which represents a risk of contamination if strictly rules of asepsis are not taken. On the other hand, the cost of each dose is lower than that of other products (ranibizumab, aflibercept) already approved for intraocular use. This allows that more patients have access to a prolonged treatment in underdeveloped or developing countries, such as Argentina. PURPOSE: To evaluate changes in visual acuity and macular thickness after intravitreal bevacizumab for the treatment of macular edema in patients with retinal vein occlusions (RVO). PATIENS AND METHODS: 39 consecutive patients with macular edema complicating RVO and treated with intravitreal injections of bevacizumab 1.25 mg/0.05 ml alone or associated with scattered peripheral laser photocoagulation, with a minimun follow-up of 18 months, were evaluated. Snellen visual acuity in LogMar units and macular thinckness measured by optical coherence tomography (OCT) were the end points. According to clinical and fluorescein angiographic presentation RVO were classified in branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO), and in non ischemic and ischemic. Wilcoxon test for paired variables, Mann Whitney for independant variables, and Student test for continuous variables, were used for statistical analysis. RESULTS: With a mean age of 66.8 years (SD: 13.65; range= 31-92 years), 62.5% of cases were CRVO and 37.5% BRVO. Mean number of injections was 4.11±161 (range= 1-6). Laser was performed in 25% of patients that did not respond to bevacizumab. At 18 months of follow-up, improvement of visual acuity and macular thickness was statistically significant (p=0.0001 and p=0.0009 respectively). BRVO showed better response to treatment than CRVO. Best visual results were obtained at first month (median= 1.00 P25= 0.5 P75= 1.30) and at 9 month (median= 0.8 P25= 0.5 P75= 1.20) after first injection, but no further improvement was observed beyond 9 months of treatment (p=0.84). No significant visual and macular thickness differences were obtained between patients treated with bevacizumab alone (p=0.116) and bevacizumab and laser (p=0.846). No ocular or systemic attributable-to-treatment side effects were observed. CONCLUSIONS: Bevacizumab was effective in improving visual acuity and reducing macular thinckness in patients with macular edema complicating RVO, especially in BRVO. No ocular or systemic complications were observed during follow-up. (AU)

Ellagitannin content, volatile composition and sensory profile of wines from different countries matured in oak barrels subjected to different toasting methods.

Ellagitannins and aromatic compounds evolution in Cabernet Sauvignon wines macerated in oak barrels for a year was studied. Identical barrels with different toastings (medium toasting, medium toasting with watering, Noisette) were used in French, Italian and USA cellars. Ellagitannins increased by 84-96% with aging time, as did woody volatiles, by 86-91% in French wines and 23-35% in Italian wines, while fruity aroma compounds declined by 50-57% in the French and Italian wines over a 12-months period. Nevertheless, other behaviors and different kinetics rates for these compounds were observed depending on barrel toasting, wine matrix and their interactions. Perceived overall woody intensity was closely related to trans-whiskey lactone, guaiacol and vanillin, whereas astringency and bitterness were significantly linked to ellagitannins (p<0.05). This is the first study that evaluates the toasting effect on wines from different countries matured in the same oak barrels.

[Folic acid: Primary prevention of neural tube defects. Literature Review]. / Ácido fólico: prevención primaria de los defectos del tubo neural. Revisión bibliográfica.

Neural tube defects (NTD) are the most common congenital malformations of the nervous system, they have a multifactorial etiology, are caused by exposure to chemical, physical or biological toxic agents, factors deficiency, diabetes, obesity, hyperthermia, genetic alterations and unknown causes. Some of these factors are associated with malnutrition by interfering with the folic acid metabolic pathway, the vitamin responsible for neural tube closure. Its deficit produce anomalies that can cause abortions, stillbirths or newborn serious injuries that cause disability, impaired quality of life and require expensive treatments to try to alleviate in some way the alterations produced in the embryo. Folic acid deficiency is considered the ultimate cause of the production of neural tube defects, it is clear the reduction in the incidence of Espina Bifida after administration of folic acid before conception, this leads us to want to further study the action of folic acid and its application in the primary prevention of neural tube defects. More than 40 countries have made the fortification of flour with folate, achieving encouraging data of decrease in the prevalence of neural tube defects. This paper attempts to make a literature review, which clarify the current situation and future of the prevention of neural tube defects.

The Emotional Brain as a Predictor and Amplifier of Chronic Pain.

Human neuroimaging studies and complementary animal experiments now identify the gross elements of the brain involved in the chronification of pain. We briefly review these advances in relation to somatic and orofacial persistent pain conditions. First, we emphasize the importance of reverse translational research for understanding chronic pain-that is, the power of deriving hypotheses directly from human brain imaging of clinical conditions that can be invasively and mechanistically studied in animal models. We then review recent findings demonstrating the importance of the emotional brain (i.e., the corticolimbic system) in the modulation of acute pain and in the prediction and amplification of chronic pain, contrasting this evidence with recent findings regarding the role of central sensitization in pain chronification, especially for orofacial pain. We next elaborate on the corticolimbic circuitry and underlying mechanisms that determine the transition to chronic pain. Given this knowledge, we advance a new mechanistic definition of chronic pain and discuss the clinical implications of this new definition as well as novel therapeutic potentials suggested by these advances.

A New Member of Family 11 Polysaccharide Lyase, Rhamnogalacturonan Lyase (CtRGLf) from Clostridium thermocellum.

A thermostable, alkaline rhamnogalacturonan lyase (RG lyase) CtRGLf, of family 11 polysaccharide lyase from Clostridium thermocellum was cloned, expressed, purified and biochemically characterised. Both, the full-length CtRGLf (80 kDa) protein and its truncated derivative CtRGL (63.9 kDa) were expressed as soluble proteins and displayed maximum activity against rhamnogalacturonan I (RG I). CtRGLf showed maximum activity at 70 °C, while CtRGL at 60 °C. Both enzymes showed maximum activity at pH 8.5. CtRGLf and CtRGL do not show higher activity on substrates with high ß-D-galactopyranose (D-Galp) substitution, this catalytic property deviates from that of some earlier characterised RG lyases which prefer substrates with high D-Galp substitution. The enzyme activity of CtRGLf and CtRGL was enhanced by 1.5 and 1.3 fold, respectively, in the presence of 3 mM of Ca(2+) ions. The TLC analysis of the degraded products of RG I, released by the action of CtRGLf and CtRGL revealed the production of RG oligosaccharides as major products confirming their endolytic activity.

Management of breech presentation at term: a retrospective cohort study of 10 years of experience.

OBJECTIVE: To evaluate the impact of management of childbirth (external cephalic version (ECV) plus planned vaginal delivery (PVD)) of breech presentation at term (⩾37 weeks of gestation). STUDY DESIGN: This retrospective cohort study was based on data collected of singleton breech presentations at term in the Obstetrics and Gynaecology Service, Cruces University Hospital (Biscay, Spain), from January 2003 to December 2012. RESULT: We attended 2377 singleton breech pregnancies at term. We attended 1684 singleton breech term deliveries, attempting vaginal delivery after selection in 52.9% of cases and were successful in 57.5% of attempts. A total of 1360 ECV were attempted, with a success rate of 50.3% of those attempted. The use of ECV has decreased the rate of breech presentation at delivery by 39.0%, the rate of breech presentation as a caesarean section (CS) indication by 47.1% (CS due to breech presentation/total of CS) and the rate of CS for breech presentation out of the total of deliveries by 39.1% (CS due to breech presentation/total of deliveries). Early postnatal parameters (5-min Apgar score, umbilical cord arterial pH and acid-base analysis) were significantly lower following PVD compared with planned CS for breech presentation. However, we did not find any differences in the rates of admissions to the neonatal unit or neonatal mortality. CONCLUSION: Management of breech presentation with a protocol that includes ECV, careful selection criteria and active management of vaginal delivery achieve a great decrease in the rate of CS for breech presentation.