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Background To evaluate whether preventive treatment can modify endothelial function and the oxidative stress profile of patients with migraines. Methods 88 treatment-naïve patients with migraines and 56 healthy sex/age matched controls underwent ultrasonography exams and blood tests at baseline, and again in the migraine patients after 3 months’ treatment with metoprolol or topiramate. Biomarkers for endothelial function and oxidative stress were analyzed. Results At baseline, patients with migraines had higher C-reactive protein (CRP; 2.55 vs. 1.64 mg/dL; p = 0.025) and lower high-density lipoprotein (HDL) cholesterol (61.7 vs. 66.8 mg/dL; p = 0.048), nitrate (19.4 vs. 27.3 µM; p = 0.037), and isoprostane levels (181 vs. 238 µM; p = 0.036) than matched controls. After treatment biomarker levels improved in patients with migraine, including CRP (2.55 mg/dL at baseline vs. 1.75 mg/dL at 3 months; p = 0.045); HDL cholesterol levels were the exception (significantly decreased). Treatment responders (> 50% reduction from baseline in migraine frequency) had higher nitrate (24.2 vs. 13.8 µM; p = 0.022) and nitrite levels (10.4 vs. 3.4 µM; p = 0.002) than non-responders after treatment. Conclusion Patients with migraines exhibit endothelial and oxidative dysfunction, which can be modified with prophylactic therapy.

Background Exhausted sugar beet pulp pellets (ESBPP) were used as raw material for lactic acid (LA) fermentation. The enzymatic hydrolysis of ESBPP was performed with the solid obtained after the fungal solid-state fermentation of ESBPP as a source of hydrolytic enzymes. Subsequently, a medium rich in glucose and arabinose was obtained, which was used to produce LA by fermentation. For LA production, two Lactobacillus strains were assayed and the effect of the supplementation of the hydrolysate with a nitrogen source and the mode of pH regulation of the fermentation were investigated. Moreover, a kinetic model for lactic acid fermentation by Lactobacillus plantarum on ESBPP hydrolysates was developed. Results L. plantarum produced a LA concentration 34 % higher than Lactobacillus casei. The highest LA concentration (30 g L-1 ) was obtained with L. plantarum when the hydrolysate was supplemented with 5 g L-1 of yeast extract and the pH was controlled with CaCO3 . The concentration of acetic acid differed depending on the concentration of CaCO3 added, producing its maximum value with 27 g L-1 of CaCO3 . The proposed kinetic model was able to predict the evolution of substrates and products depending on the variation of the pH in the hydrolysate, according to the amount of CaCO3 added. Conclusion ESBPP can be revalorized to produce lactic acid. A pure LA stream or a mixture of lactic and acetic acid, depending on the pH control method of the fermentation, can be produced. Thus, this control shows a great interest depending on the destination of the effluent. This article is protected by copyright. All rights reserved.

Treatment preferences are considered a relevant decision-making driver by the main atrial fibrillation (AF) guidelines. Direct Oral Anticoagulants (DOACs), considered as similar clinically, have administration differences useful for treatment individualization. Preferences, priorities and satisfaction of DOAC users were assessed through an observational, multicentric (25 hospitals), cross-sectional study including adult AF-patients (and/or caregivers) in Spain. Three study groups were considered according to DOAC posology preferences: (A) once-daily, with water; (B) once-daily, with food; (C) twice-daily. Overall, 332 patients and 55 caregivers were included. Mean (SD) age was 73.7 (10.7) years [58.7 (13.9) for caregivers]; 51.5% women [69.1% for caregivers]; 80.7% showed comorbidities and poly-pharmacy [6.6 (3.3) drugs/day]. No statistically significant differences were shown among study groups. Once-daily administration was preferred by 274 patients (82.5%) [60.8% (Group A); 21.7% (Group B); 17.5% (Group C)], and 47 caregivers (85.5%) [58.2% (Group A); 27.3% (Group B); 14.5% (Group C)]. Once-daily DOACs were prescribed in 42.8% of the patients. Bleeding risk was the main concern for both, patients and caregivers, followed by DOAC posology and interactions. Although treatment satisfaction (patients and caregivers) was high (9.0 and 9.1 points, respectively), match between individual treatment preferences and real prescriptions was only shown in 41.0% of AF-patients, evidencing a need for patient involvement on treatment decision-making. There is not a patient profile linked to treatment preferences, and clinical criteria must be the main driver for decision-making. However, for most AF-patients (elderly patients), aged, with comorbidity, poly-pharmacy and high cardiovascular risk, once-daily DOACs would be the preferred option. Electronic supplementary material The online version of this article (10.1007/s11239-020-02194-5) contains supplementary material, which is available to authorized users.

Background Exhausted sugar beet pulp pellets (ESBPP), a sugar industry by-product generated after sugar extraction in the sugar production process, have been used as a raw material for lactic acid (LA) production via hydrolysis and fermentation by Lactobacillus casei. To design a more cost-effective process, simultaneous saccharification and fermentation (SSF) of ESBPP is proposed in the present study. The effects of pH control, nutrient supplementation and solid addition in fed-batch SSF on lactic acid production were investigated. Results The highest LA concentration (26.88 g L-1 ) was reached in fed-batch SSF at a solid/liquid loading of 0.2 g mL-1 , with pH control (by adding 30 g L-1 CaCO3 to the medium) and nutrient supplementation (by adding 20 mL of MRS medium per 100 mL of buffer). Under these conditions, a maximum productivity of 0.63 g L-1 h-1 was achieved, which is 2.7 times higher than that attained in the control experiment (SSF inoculated at time 0 h). However, a slightly lower LA yield was obtained, revealing the need of an increasing dose of enzymes at high solid loading SSF. Conclusion An efficient fed-batch SSF strategy with pH control and MRS supplementation is described in the present study, attaining higher LA productivity compared to separate hydrolysis and fermentation and SSF. © 2020 Society of Chemical Industry.

Exhausted sugar beet pulp (ESBP), a by-product of the sugar industry, has been used as a substrate to produce lactic acid (LA). Due to the fact that ESBP contains a high percentage of pectin and hemicellulose, different pretreatments were studied to solubilize them and to facilitate the access to cellulose in the subsequent enzymatic hydrolysis. Several pretreatments were studied, specifically biological, oxidant with alkaline hydrogen peroxide (AHP), and thermochemical with acid (0.25, 0.5, or 1% w/v of H2SO4). Pretreated ESBP was enzymatically hydrolysed and fermented with the strain Lactiplantibacillus plantarum for LA production. The hydrolysis was carried out with the commercial enzymes Celluclast, pectinase, and xylanase, for 48 h. After that, the hydrolysate was supplemented with yeast extract and calcium carbonate before the bacteria inoculation. Results showed that all the pretreatments caused a modification of the fibre composition of ESBP. In most cases, the cellulose content increased, rising from 25% to 68% when ESBP was pretreated thermochemically at 1% w/v H2SO4. The production of LA was enhanced when ESBP was pretreated thermochemically. However, it was reduced when biological and AHP pretreatments were applied. In conclusion, thermochemical pretreatment with 1% w/v H2SO4 had a positive impact on the production of LA, increasing its concentration from 27 g/L to 50 g/L., This research was funded by "Ministerio de Economia, Industria y Competitividad", "Agencia Estatal de Investigacion (AEI)" and "Fondo Europeo de Desarrollo Regional (FEDER)" (CTM2016-79071-R).

In this study, the production of a hydrolysate rich in fermentable sugars, which could be used as a generic microbial culture medium, was carried out by using exhausted sugar beet pulp pellets (ESBPPs) as raw material. For this purpose, the hydrolysis was performed through the direct addition of the fermented ESBPPs obtained by fungal solid-state fermentation (SSF) as an enzyme source. By directly using this fermented solid, the stages for enzyme extraction and purification were avoided. The effects of temperature, fermented to fresh solid ratio, supplementation of fermented ESBPP with commercial cellulase, and the use of high-solid fed-batch enzymatic hydrolysis were studied to obtain the maximum reducing sugar (RS) concentration and productivity. The highest RS concentration and productivity, 127.3 g&middot, L&minus, 1 and 24.3 g&middot, 1&middot, h&minus, 1 respectively, were obtained at 50 &deg, C and with an initial supplementation of 2.17 U of Celluclast&reg, per gram of dried solid in fed-batch mode. This process was carried out with a liquid to solid ratio of 4.3 mL&middot, g&minus, 1 solid, by adding 15 g of fermented solid and 13.75 g of fresh solid at the beginning of the hydrolysis, and then the same amount of fresh solid 3 times every 2.5 h. By this procedure, ESBPP can be used to produce a generic microbial feedstock, which contains a high concentration of monosaccharides.

Nowadays, significant amounts of agro-industrial wastes are discarded by industries; however, they represent interesting raw materials for the production of high-added value products. In this regard, orange peels (ORA) and exhausted sugar beet cossettes (ESBC) have turned out to be promising raw materials for hydrolytic enzymes production by solid state fermentation (SSF) and also a source of sugars which could be fermented to different high-added value products. The maximum activities of xylanase and exo-polygalacturonase (exo-PG) measured in the enzymatic extracts obtained after the SSF of ORA were 31,000 U·kg-1 and 17,600 U·kg-1, respectively; while for ESBC the maximum values reached were 35,000 U·kg-1 and 28,000 U·kg-1, respectively. The enzymatic extracts obtained in the SSF experiments were also employed for the hydrolysis of ORA and ESBC. Furthermore, it was found that extracts obtained from SSF of ORA, supplemented with commercial cellulase, were more efficient for the hydrolysis of ORA and ESBC than a commercial enzyme cocktail typically used for this purpose. In this case, maximum reducing sugars concentrations of 57 and 47 g·L-1 were measured after the enzymatic hydrolysis of ESBC and ORA, respectively.

Exhausted sugar beet cossettes (ESBC) show an enormous potential as a source of sugars for the production of bio-products. Enzyme hydrolysis with the combined effect of mainly cellulases, xylanases and pectinases, turned out to be very efficient, obtaining almost double the concentration of sugars measured with the sole action of Celluclast® and β-glucosidase, and increasing 5 times the hydrolysis rate. As the sole pretreatment, ESBC soaked in the hydrolysis buffer were autoclaved, avoiding the application of severe conventional biomass pretreatments. Moreover, a promising alternative for the complete utilization of glucose, xylose, arabinose, mannose and maltose contained in ESBC is proposed in this paper. It consists of sequential fermentation of sugars released in the hydrolysis step to produce bioethanol and lactic acid as main bio-products. Compared to separate fermentations, with this strategy glucose and hemicellulose derived sugars were completely consumed and the 44% of pectin derived sugars.

The chemical composition of sugar beet roots makes this raw material an attractive feedstock for ethanol fermentation. In the manufacture of sugar from this crop, various intermediates, by-products, and wastes are generated, which can be used for the production of energy and other value-added products, such as biofuels. In this chapter, the current processes for the conversion of the sugary juices (raw, thin, and thick juices), molasses and sugar beet pulp into bioethanol are described. In addition, the economics of sugar beet ethanol and the principal strategies proposed for increasing bioethanol yields are described.

Purpose To explore adherence to oral hormone treatment in patients with metastatic prostate cancer (mCRPC) and to identify the factors that influence it. Methods A qualitative exploratory study was conducted at the National Cancer Institute of Rome. Patients aged >18 years with castration-resistant prostate cancer (mCRPC) and who were using oral hormone drugs were recruited. Semi-structured interviews were used for data collection, subsequently transcribed verbatim and analysed using Ritchie and Spencer's framework analysis. Results The sample included 13 patients with a median age of 72 who were treated, on average, for seven months with abiraterone acetate (AA) (76.9%) and enzalutamide (ENZ) (23.1%). Five themes were identified: expression of the concept of adherence, favouring factors, obstacle factors, functional strategies and levels of adherence. Conclusions The patients express a good level of adherence, which they define in different ways—the helping relationship with the attending physician, the support of the family members and the few side effects of the drugs. For the future, it is recommended to perform a multicentre mixed method study to explain the levels of adherence and distress in women with breast cancer.

In recent years, direct oral anticoagulants (DOACs) have become an alternative to vitamin K antagonists (VKA) for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) as well as for prevention and treatment of deep venous thrombosis. Pivotal trials have demonstrated non-inferiority and potential superiority compared to warfarin, which increases the options of anticoagulant treatment. In our setting, the Anticoagulant Treatment Units (ATUs) and Primary Care Centres (PCCs) play an important role in the education, follow-up, adherence control and management in special situations of anticoagulated patients. These considerations have motivated us to elaborate the present consensus document that aims to establish clear recommendations that incorporate the findings of scientific research into clinical practice to improve the quality of care in the field of anticoagulation.A group of experts from the Catalan Thrombosis Group (TROMBOC@T) reviewed all published literature from 2009 to 2016, in order to provide recommendations based on clinical evidence.As a result of the project, a set of practical recommendations have been established that will facilitate treatment, education, follow-up and management in special situations of anticoagulated patients with ACODs.Progressive increase in the use of DOACs calls for measures to establish and homogenise clinical management guidelines for patients anticoagulated with DOACs in ATUs and PCCs.

Resumen Antecedentes y objetivos En los ultimos anos los anticoagulantes orales directos (ACOD) se han convertido en una alternativa a los antagonistas de la vitamina K (AVK) para la prevencion del ictus y embolia sistemica en pacientes con fibrilacion auricular no valvular (FANV), asi como para la prevencion y tratamiento de la trombosis venosa profunda. Los ensayos clinicos han demostrado la no inferioridad y la potencial superioridad en comparacion con la warfarina, lo cual permite ampliar las opciones de anticoagulacion. En nuestro medio, las Unidades de Tratamiento Anticoagulante (UTA) y los Centros de Atencion Primaria (CAP) son los encargados de la educacion, seguimiento, control de adherencia y del manejo en situaciones especiales de los pacientes anticoagulados. Estas consideraciones han motivado la preparacion del presente documento de consenso, que tiene como objetivo establecer recomendaciones que incorporen los hallazgos de la investigacion cientifica a la practica clinica para mejorar la calidad asistencial en el ambito de la anticoagulacion. Material y metodos Un grupo de expertos del Grupo Catalan de Trombosis (TROMBOC@T) ha revisado la bibliografia publicada entre 2007 y 2016 para poder establecer recomendaciones basadas en la evidencia clinica. Resultados Como resultado del proyecto se han establecido un conjunto de recomendaciones de caracter practico que facilitaran el tratamiento, educacion, seguimiento y manejo en situaciones especiales de los pacientes anticoagulados con ACOD. Conclusiones El aumento progresivo del uso de los ACOD requiere establecer y homogeneizar las directrices de actuacion clinica en el paciente anticoagulado con estos antitromboticos tanto en las UTA como en los CAP.

The present report describes the value of the plasma determination of TNF-alpha, at diagnosis, in 43 patients with non-Hodgkin's lymphoma (NHL), related to their clinical presentation and the new International Prognosis Index (IPI). We also compare the levels of TNF-alpha with those of LDH, beta-2-microglobulin (beta-2-m), and ferritin. At diagnosis, the mean values of the quotients between the marker values and the maximum value of normal (ratio:r-) are placed 7 times higher than normal for r-TNF-alpha, whereas those of r-beta-2-m and r-LDH are 2,4 and 1,4 times more respectively. We found a relationship between the value of r-TNF-alpha and the ECOG, Ann Arbor stage, the number of affected extranodal sites, and between the values of r-beta-2-m with r-LDH. The best correlation was obtained between the values of r-TNF-alpha and r-beta-2-m and IPI, however r-TNF-alpha best stratify the four risk groups in this prognosis index.