Microbial torularhodin - a comprehensive review.

The demand for food, feed, cosmeceutical, and nutraceutical supplements/additives from natural sources has been rapidly increasing, with expectations for a faster expansion than the growth of the global markets in the coming years. In this framework, a particular interest is given to carotenoids due to their outstanding antioxidant activities, particularly the xanthophylls class. Torularhodin is one of these carotenoids that stands out for its multifunctional role as: antioxidant, anticancer and antimicrobial, yet its commercial potential is still unexplored. Although most xanthophylls can be naturally found in: microbial, plant and animal sources, torularhodin is only produced by microbial species, especially red oleaginous yeast. The microbial production of xanthophylls has many advantages as compared to other natural sources, such as: the need for low production area, easier extraction, high yields (at optimum operating conditions), and low (or no) seasonal, climatic, and geographic variation dependency. Due to the importance of natural products and their relevance to the market, this review provides a comprehensive overview of the: properties, characteristics and potential health benefits of torularhodin. Moreover, the most promising developments in both upstream and downstream processing to obtain this colorant from microbial sources are considered. For this purpose, the main microorganisms used for torularhodin production are firstly reviewed, including biosynthesis pathway and torularhodin properties. Following, an overall analysis of the processing aspects related with its: extraction, separation and purification is provided. Lastly, current status and future trends of torularhodin-based processes and products such as therapeutic agents or biomaterials are discussed, indicating promising directions toward biorefinery and circular economy.

Green solvents extraction-based detoxification to enhance the enzymatic hydrolysis of steam-exploded lignocellulosic biomass and recover bioactive compounds.

A novel strategy for pre-treated biomass detoxification combining emerging green solvents and low environmental impact extraction technologies was evaluated. Steam-exploded biomass was subjected to microwave-assisted or orbital shaking extraction using bio-based or eutectic solvents. The extracted biomass was enzymatically hydrolysed. The potential of this detoxification methodology was studied in terms of phenolic inhibitors extraction and sugar production improvement. The effect of adding a post-extraction water washing step before hydrolysis was also evaluated. Excellent results were achieved when steam-exploded biomass was subjected to the microwave-assisted extraction combined with the washing step. The highest sugar production was achieved when ethyl lactate was used as extraction agent (49.80 ± 3.10 g total sugar/L) over the control (30.43 ± 0.34 g total sugar/L). Results suggested that a detoxification step based on green solvents would be a promising option to extract phenolic inhibitors, which can be revalorized as antioxidants, and improve the sugar production from the extracted pre-treated biomass.

Enhanced Recovery of Natural Antioxidants from Grape Waste Using Natural Eutectic Solvents-Based Microwave-Assisted Extraction.

The evaluation of sustainable solvents as alternatives to more harmful conventional solvents combined with intensification techniques to recover phenolic compounds from agri-food waste is in the spotlight. The wine industry generates large amounts of waste as a consequence of grape processing operations, which can be revalued by solvent extraction of valuable antioxidants for food and fine chemical applications. Therefore, the present study focuses on the use of natural eutectic solvents (NAESs) with benign environmental, health, and safety profiles, for valorization of grape waste in the context of a circular economy. Herein, up to 15 NAESs consisting of combinations of three hydrogen bond acceptors (choline chloride, L-proline, and betaine) and four hydrogen bond donors (1,2-propanediol, glycerol, and 1,2- and 1,3-butanediol) were evaluated for antioxidant recovery. After an initial screening of the performance of NAESs by conventional extraction, the process was intensified by microwave-assisted extraction (MAE). The extracts were analyzed by UV/VIS spectrophotometric and HPLC methods. Promising results were obtained with the solvent betaine, 1,2-butanediol [1:4], using MAE at 100 °C for 3 min. Overall, the proposed NAESs-based MAE method was successfully applied to recover target compounds from grape waste, with great prospects for the antioxidants market and sustainable development for the winery sector.

Clinical Results of the Advanced Neurovascular Access Catheter System Combined With a Stent Retriever in Acute Ischemic Stroke (SOLONDA).

BACKGROUND: The Advanced Neurovascular Access (ANA) thrombectomy system is a novel stroke thrombectomy device comprising a self-expanding funnel designed to reduce clot fragmentation by locally restricting flow while becoming as wide as the lodging artery. Once deployed, the ANA device allows distal aspiration combined with a stent retriever to mobilize the clot into the funnel where it remains copped during extraction. We investigated the safety and efficacy of ANA catheter system. METHODS: SOLONDA (Solitaire in Combination With the ANA Catheter System as Manufactured by Anaconda) was a prospective, open, single-arm, multicenter trial with blinded assessment of the primary outcome by an independent core lab. Patients with anterior circulation vessel occlusion admitted within 8 hours from symptom onset were eligible. The primary end point was successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3) with ≤3 passes of the ANA device in combination with stent retriever, before the use of rescue therapy in the intention to treat population. Primary predefined analysis was noninferiority as compared to the performance end point observed in HERMES (High Effective Reperfusion Using Multiple Endovascular Devices). RESULTS: After enrollment of 74 patients, an interim analysis was conducted, and the trial Steering Committee decided to terminate recruitment due to safety and performance objectives were reached. Mean age was 71.6 (SD 8.9) years, 46.6% women and median National Institutes of Health Stroke Scale on admission 14 (interquartile range, 10-19). Successful reperfusion within 3 passes before rescue therapy was achieved in 60/72 (83.3% [95% CI, 74.7%-91.9%]) with a rate of complete reperfusion (modified Thrombolysis in Cerebral Infarction score 2c-3) of 60% (95% CI, 48.4%-71.1%; 43/72 patients). After noninferiority was confirmed (P<0.01), the ANA device also showed superiority in the rate of successful reperfusion with ≤3 passes (P=0.02). First-pass successful recanalization rate was 55.6% (95% CI, 44.1%-67.0%), with a first-pass complete recanalization rate of 38.9% (95% CI, 27.6%-50.1%). Rescue therapy to obtain a modified Thrombolysis in Cerebral Infarction score 2b-3 was needed in 12/72 (17%) patients. At 90 days, the rate of favorable functional outcome (modified Rankin Scale score 0-2) was 57.5% (95% CI, 46.2%-68.9%), and the rate of excellent functional outcome (modified Rankin Scale score 0-1) was 45.2% (95% CI, 33.8%-56.6%). The rate of severe adverse device related was 1.4%. CONCLUSIONS: In this clinical experience, the ANA device achieved a high rate of complete recanalization with a preliminary good safety profile and favorable 90 days clinical outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04095767.

Primary endovascular treatment for acute ischemic stroke in teenage patients: a short case series.

PURPOSE: To analyze the safety and efficacy of primary endovascular treatment (EVT) for acute ischemic stroke (AIS) in patients younger than 18 years of age. METHODS: Review of 4 patients < 18 years of age with AIS, prospectively enrolled in an electronic database registry for acute ischemic stroke patients who underwent thrombectomy at tertiary centers, from January 2011 to February 2017. Clinical and imaging data were analyzed. RESULTS: All patients were female. Patients 1 to 4 were 14, 13, 16, and 13 years old, respectively. Patients 1 and 3 had left middle cerebral artery occlusion, patient 2 basilar occlusion, and patient 4 right tandem occlusion. Mean NIHSS score was 13 (7-19) on arrival and 4 (0-5) at 24 h. Patient 2 had Osler-Weber-Rendu disease and patient 4 a previously surgically repaired complete atrioventricular canal. All patients presented with clinical-radiological mismatch. CT/CTA was used in patients 1 and 4 and MRI/MRA in patients 2 and 3. Stent retriever was used in 3 patients (patients 1, 3, and 4) and direct aspiration first-pass technique in 1 (patient 2). All 4 procedures resulted in successful recanalization and 3-month functional independence. CONCLUSION: Primary EVT is reported in patients 13 to 16 years of age with AIS due to large vessel occlusion and clinical-radiological mismatch. Procedures were safe and effective with prompt recanalization and good clinical outcome.

Thrombectomy within 8 hours after symptom onset in ischemic stroke.

BACKGROUND: We aimed to assess the safety and efficacy of thrombectomy for the treatment of stroke in a trial embedded within a population-based stroke reperfusion registry. METHODS: During a 2-year period at four centers in Catalonia, Spain, we randomly assigned 206 patients who could be treated within 8 hours after the onset of symptoms of acute ischemic stroke to receive either medical therapy (including intravenous alteplase when eligible) and endovascular therapy with the Solitaire stent retriever (thrombectomy group) or medical therapy alone (control group). All patients had confirmed proximal anterior circulation occlusion and the absence of a large infarct on neuroimaging. In all study patients, the use of alteplase either did not achieve revascularization or was contraindicated. The primary outcome was the severity of global disability at 90 days, as measured on the modified Rankin scale (ranging from 0 [no symptoms] to 6 [death]). Although the maximum planned sample size was 690, enrollment was halted early because of loss of equipoise after positive results for thrombectomy were reported from other similar trials. RESULTS: Thrombectomy reduced the severity of disability over the range of the modified Rankin scale (adjusted odds ratio for improvement of 1 point, 1.7; 95% confidence interval [CI], 1.05 to 2.8) and led to higher rates of functional independence (a score of 0 to 2) at 90 days (43.7% vs. 28.2%; adjusted odds ratio, 2.1; 95% CI, 1.1 to 4.0). At 90 days, the rates of symptomatic intracranial hemorrhage were 1.9% in both the thrombectomy group and the control group (P=1.00), and rates of death were 18.4% and 15.5%, respectively (P=0.60). Registry data indicated that only eight patients who met the eligibility criteria were treated outside the trial at participating hospitals. CONCLUSIONS: Among patients with anterior circulation stroke who could be treated within 8 hours after symptom onset, stent retriever thrombectomy reduced the severity of post-stroke disability and increased the rate of functional independence. (Funded by Fundació Ictus Malaltia Vascular through an unrestricted grant from Covidien and others; REVASCAT ClinicalTrials.gov number, NCT01692379.).

Molecular and Thermodynamic Properties of Zwitterions versus Ionic Liquids: A Comprehensive Computational Analysis to Develop Advanced Separation Processes.

Zwitterion ionic liquids (ZIs) are compounds in which both counterions are covalently tethered, conferring them with unique characteristics; however, most of their properties are still unknown, representing a bottleneck to exploit their practical applications. Herein, the molecular and fluid properties of ZIs and their mixtures were explored by means of quantum chemical analysis based on the density functional theory (DFT) and COSMO-RS method, and compared against homologous ionic liquids (ILs) to provide a comprehensive overview of the effect of the distinct structures on their physicochemical and thermodynamic behavior. Overall, ZIs were revealed as compounds with higher polarity and stronger hydrogen-bonding capacity, implying higher density, viscosity, melting point, and even lower volatility than structurally similar ILs. The phase equilibrium of binary and ternary systems supports stronger attractive interactions between ZIs and polar compounds, whereas higher liquid-liquid immiscibility with nonpolar compounds may be expected. Ultimately, the performance of ZIs in the wider context of separation processes is illustrated, while providing molecular insights to allow their selection and design for relevant applications.

Outcomes After Direct Thrombectomy or Combined Intravenous and Endovascular Treatment Are Not Different.

BACKGROUND AND PURPOSE: Whether intravenous thrombolysis adds a further benefit when given before endovascular thrombectomy (EVT) is unknown. Furthermore, intravenous thrombolysis delays time to groin puncture, mainly among drip and ship patients. METHODS: Using region-wide registry data, we selected cases that received direct EVT or combined intravenous thrombolysis+EVT for anterior circulation strokes between January 2011 and October 2015. Treatment effect was estimated by stratification on a propensity score. The average odds ratios for the association of treatment with good outcome and death at 3 months and symptomatic bleedings at 24 hours were calculated with the Mantel-Haenszel test statistic. RESULTS: We included 599 direct EVT patients and 567 patients with combined treatment. Stratification through propensity score achieved balance of baseline characteristics across treatment groups. There was no association between treatment modality and good outcome (odds ratio, 0.97; 95% confidence interval, 0.74-1.27), death (odds ratio, 1.07; 95% confidence interval, 0.74-1.54), or symptomatic bleedings (odds ratio, 0.56; 95% confidence interval, 0.25-1.27). CONCLUSIONS: This observational study suggests that outcomes after direct EVT or combined intravenous thrombolysis+EVT are not different. If confirmed by a randomized controlled trial, it may have a significant impact on organization of stroke systems of care.

Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.

BACKGROUND: In 2015, five randomised trials showed efficacy of endovascular thrombectomy over standard medical care in patients with acute ischaemic stroke caused by occlusion of arteries of the proximal anterior circulation. In this meta-analysis we, the trial investigators, aimed to pool individual patient data from these trials to address remaining questions about whether the therapy is efficacious across the diverse populations included. METHODS: We formed the HERMES collaboration to pool patient-level data from five trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA) done between December, 2010, and December, 2014. In these trials, patients with acute ischaemic stroke caused by occlusion of the proximal anterior artery circulation were randomly assigned to receive either endovascular thrombectomy within 12 h of symptom onset or standard care (control), with a primary outcome of reduced disability on the modified Rankin Scale (mRS) at 90 days. By direct access to the study databases, we extracted individual patient data that we used to assess the primary outcome of reduced disability on mRS at 90 days in the pooled population and examine heterogeneity of this treatment effect across prespecified subgroups. To account for between-trial variance we used mixed-effects modelling with random effects for parameters of interest. We then used mixed-effects ordinal logistic regression models to calculate common odds ratios (cOR) for the primary outcome in the whole population (shift analysis) and in subgroups after adjustment for age, sex, baseline stroke severity (National Institutes of Health Stroke Scale score), site of occlusion (internal carotid artery vs M1 segment of middle cerebral artery vs M2 segment of middle cerebral artery), intravenous alteplase (yes vs no), baseline Alberta Stroke Program Early CT score, and time from stroke onset to randomisation. FINDINGS: We analysed individual data for 1287 patients (634 assigned to endovascular thrombectomy, 653 assigned to control). Endovascular thrombectomy led to significantly reduced disability at 90 days compared with control (adjusted cOR 2.49, 95% CI 1.76-3.53; p<0.0001). The number needed to treat with endovascular thrombectomy to reduce disability by at least one level on mRS for one patient was 2.6. Subgroup analysis of the primary endpoint showed no heterogeneity of treatment effect across prespecified subgroups for reduced disability (pinteraction=0.43). Effect sizes favouring endovascular thrombectomy over control were present in several strata of special interest, including in patients aged 80 years or older (cOR 3.68, 95% CI 1.95-6.92), those randomised more than 300 min after symptom onset (1.76, 1.05-2.97), and those not eligible for intravenous alteplase (2.43, 1.30-4.55). Mortality at 90 days and risk of parenchymal haematoma and symptomatic intracranial haemorrhage did not differ between populations. INTERPRETATION: Endovascular thrombectomy is of benefit to most patients with acute ischaemic stroke caused by occlusion of the proximal anterior circulation, irrespective of patient characteristics or geographical location. These findings will have global implications on structuring systems of care to provide timely treatment to patients with acute ischaemic stroke due to large vessel occlusion. FUNDING: Medtronic.

Association Between Time to Reperfusion and Outcome Is Primarily Driven by the Time From Imaging to Reperfusion.

BACKGROUND AND PURPOSE: A progressive decline in the odds of favorable outcome as time to reperfusion increases is well known. However, the impact of specific workflow intervals is not clear. METHODS: We studied the mechanical thrombectomy group (n=103) of the prospective, randomized REVASCAT (Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset) trial. We defined 3 workflow metrics: time from symptom onset to reperfusion (OTR), time from symptom onset to computed tomography, and time from computed tomography (CT) to reperfusion. Clinical characteristics, core laboratory-evaluated Alberta Stroke Program Early CT Scores (ASPECTS) and 90-day outcome data were analyzed. The effect of time on favorable outcome (modified Rankin scale, 0-2) was described via adjusted odds ratios (ORs) for every 30-minute delay. RESULTS: Median admission National Institutes of Health Stroke Scale was 17.0 (14.0-20.0), reperfusion rate was 66%, and rate of favorable outcome was 43.7%. Mean (SD) workflow times were as follows: OTR: 342 (107) minute, onset to CT: 204 (93) minute, and CT to reperfusion: 138 (56) minute. Longer OTR time was associated with a reduced likelihood of good outcome (OR for 30-minute delay, 0.74; 95% confidence interval [CI], 0.59-0.93). The onset to CT time did not show a significant association with clinical outcome (OR, 0.87; 95% CI, 0.67-1.12), whereas the CT to reperfusion interval showed a negative association with favorable outcome (OR, 0.72; 95% CI, 0.54-0.95). A similar subgroup analysis according to admission ASPECTS showed this relationship for OTR time in ASPECTS<8 patients (OR, 0.56; 95% CI, 0.35-0.9) but not in ASPECTS≥8 (OR, 0.99; 95% CI, 0.68-1.44). CONCLUSIONS: Time to reperfusion is negatively associated with favorable outcome, being CT to reperfusion, as opposed to onset to CT, the main determinant of this association. In addition, OTR was strongly associated to outcome in patients with low ASPECTS scores but not in patients with high ASPECTS scores. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01692379.

Solubility of CO2 in [1-n-butylthiolanium][Tf2N]+toluene mixtures: liquid-liquid phase split separation and modelling.

Carbon dioxide has been shown to be an effective antisolvent gas for separating organic compounds from ionic liquids (ILs) by inducing a liquid-vapour to liquid-liquid-vapour transition. Using carbon dioxide, toluene can be separated from imidazolium, phosphonium and pyridinum cation-based ILs with the bis(trifluoromethylsulfonyl)imide anion, which is relatively hydrophobic and has a high toluene solubility. A new IL with relatively low viscosity is tested here for the same toluene separation process: 1-n-butylthiolanium bis(trifluoromethylsulfonyl)imide. Carbon dioxide solubility in binary and ternary systems containing toluene and 1-n-butylthiolanium bis(trifluoromethylsulfonyl)imide is measured at 298.15 and 313.15 K up to 7.4 MPa. Solubility behaviour in this IL is similar to imidazolium-based ILs with the same anion. However, phase split pressures are lower when 1-n-butylthiolanium bis (trifluoromethylsulfonyl)imide is used instead of 1- n-hexyl-3-methylimidazolium bis(trifluoromethylsu- lfonyl)imide at the same conditions of temperature and initial composition of toluene in the IL. Solubility data are modelled with the conductor-like screening model for real solvents combined with the Soave-Redlich-Kwong equation of state, which provides good qualitative results.

Outcomes of a contemporary cohort of 536 consecutive patients with acute ischemic stroke treated with endovascular therapy.

BACKGROUND AND PURPOSE: We sought to assess outcomes after endovascular treatment/therapy of acute ischemic stroke, overall and by subgroups, and looked for predictors of outcome. METHODS: We used data from a mandatory, population-based registry that includes external monitoring of completeness, which assesses reperfusion therapies for consecutive patients with acute ischemic stroke since 2011. We described outcomes overall and by subgroups (age ≤ or >80 years; onset-to-groin puncture ≤ or >6 hours; anterior or posterior strokes; previous IV recombinant tissue-type plasminogen activator or isolated endovascular treatment/therapy; revascularization or no revascularization), and determined independent predictors of good outcome (modified Rankin Scale score ≤2) and mortality at 3 months by multivariate modeling. RESULTS: We analyzed 536 patients, of whom 285 received previous IV recombinant tissue-type plasminogen activator. Overall, revascularization (modified Thrombolysis In Cerebral Infarction scores, 2b and 3) occurred in 73.9%, 5.6% developed symptomatic intracerebral hemorrhages, 43.3% achieved good functional outcome, and 22.2% were dead at 90 days. Adjusted comparisons by subgroups systematically favored revascularization (lower proportion of symptomatic intracerebral hemorrhages and death rates and higher proportion of good outcome). Multivariate analyses confirmed the independent protective effect of revascularization. Additionally, age >80 years, stroke severity, hypertension (deleterious), atrial fibrillation, and onset-to-groin puncture ≤6 hours (protective) also predicted good outcome, whereas lack of previous disability and anterior circulation strokes (protective) as well as and hypertension (deleterious) independently predicted mortality. CONCLUSIONS: This study reinforces the role of revascularization and time to treatment to achieve enhanced functional outcomes and identifies other clinical features that independently predict good/fatal outcome after endovascular treatment/therapy.

Extraction of 5-Hydroxymethylfurfural and Furfural in Aqueous Biphasic Systems: A COSMO-RS Guided Approach to Greener Solvent Selection.

5-Hydroxymethylfurfural (HMF) and furfural (Fur) are promising biobased platform chemicals, derived from the dehydration of carbohydrate feedstocks, normally conducted in an aqueous phase. Plagued by side-reactions in such phase, such as the rehydration to levulinic acid (LA) and formic acid (FA) or self-condensation to humins, HMF and Fur necessitates diversification from monophasic aqueous reaction systems toward biphasic systems to mitigate undesired side-reactions. Here, a methodology based on the COnductor-like Screening MOdel for Real Solvents (COSMO-RS) method was used to screen solvent candidates based on the predicted partition coefficients (Ki). Hansen solubility parameters in conjunction with excess thermodynamic quantities determined by COSMO-RS were employed to assess solvent compatibility. Experimental validation of the COSMO-RS values highlighted only minor deviations from the predictions with root-mean-square-error (RMSE) values of HMF and Fur at 0.76 and 5.32, respectively, at 298 K. The combined effort suggested cyclohexanone, isophorone, and methyl isobutyl ketone (MIBK) as the best candidates. Finally, extraction solvent reuse demonstrated cyclohexanone suitability for HMF extraction with KHMF of 3.66 and MIBK for Fur with KFur 7.80 with consistent partitioning across four total runs. Both solvents are classified as recommended by the CHEM21 solvent selection guide, hence adding to the sustainability of the process.

Recovery of Phenolic Compounds from Orange Peel Waste by Conventional and Assisted Extraction Techniques Using Sustainable Solvents.

BACKGROUND: The valorization of orange peel waste (OPW) through the extraction of bioactive compounds is a clear example of the circular economy. OPW contains many value-added compounds, among which bioactive phenolic compounds (flavonoids and phenolic acids) could be extracted and used for industrial applications, such as pharmaceuticals or cosmetics. METHODS: In this work, the extraction of phenolic compounds from orange peel was carried out by conventional (orbital shaker) and assisted (ultrasound and microwave) extraction techniques using deionized water, 80% (v/v) ethanol in water, and ethyl acetate as solvents. The effect of temperature, extraction time, and type of technique was evaluated and discussed following spectrophotometric (total phenolic content and total flavonoid content) and high-performance liquid chromatography (HPLC) analyses of the extracts. RESULTS: The most effective extraction in terms of efficiency was achieved by microwave-assisted extraction using 80% (v/v) ethanol in water as the extraction solvent, at 373 K for 6 min, which obtained 7.2 ± 0.1 mg gallic acid equivalent (GAE)/g OPW and 13.3 ± 0.1 mg quercetin equivalent (QE)/g OPW, with the main bioactive compound extracted being hesperidin (58.2 ± 0.2 mg/g OPW). The most effective extraction in terms of energy consumption was achieved using ultrasound-probe-assisted extraction, yielding 8.8 ± 0.0 mg GAE/g OPW; 17.1 ± 0.1 mg QE/g OPW; 40.0 ± 0.2 mg hesperidin/g OPW, with an energy consumption of 18 kJ. CONCLUSIONS: Ultrasound and microwave-assisted extractions can be considered efficient extraction technologies for the valorization of OPW as they reduce extraction time and energy consumption and increase extraction yield.

Posterior Fossa Venous Drainage.

This paper aims to make simple the evaluation of the main veins related to the brainstem and cerebellum. Posterior fossa venous drainage is best understood in context with its three main collectors: superior: toward the Vein of Galen; posterior: toward the torcular complex; and anterior: toward the superior petrosal sinus. A fourth possible drainage path, often harder to distinguish, is directed toward the inferior petrosal sinus. Veins of these four systems are frequently connected to one another. Despite traditionally being considered less regular than its arterial disposition, posterior fossa venous anatomy follows specific patterns that are easy to identify. The three more representative veins of each venous confluent have been selected, to help in recognizing them angiographically. Since pial large veins are primarily located over the surface of the encephalon, most related anatomical structures can be confidently identified. This is of special interest when angiographic 2D or 3D studies are evaluated and provide fundamental assistance in locating precise structures. To better aid in understanding venous disposition, an overview of embryologic and fetal development is also discussed.

Pre-clinical Models of Metastasis in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a hostile solid malignancy coupled with an extremely high mortality rate. Metastatic disease is already found in most patients at the time of diagnosis, resulting in a 5-year survival rate below 5%. Improved comprehension of the mechanisms leading to metastasis is pivotal for the development of new targeted therapies. A key field to be improved are modeling strategies applied in assessing cancer progression, since traditional platforms fail in recapitulating the complexity of PDAC. Consequently, there is a compelling demand for new preclinical models that mirror tumor progression incorporating the pressure of the immune system, tumor microenvironment, as well as molecular aspects of PDAC. We suggest the incorporation of 3D organoids derived from genetically engineered mouse models or patients as promising new tools capable to transform PDAC pre-clinical modeling and access new frontiers in personalized medicine.

Sensitivity of Acute Myelocytic Leukemia Cells to the Dienone Compound VLX1570 Is Associated with Inhibition of the Ubiquitin-Proteasome System.

Dienone compounds with a 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore have been widely reported to show tumor cell selectivity. These compounds target the ubiquitin-proteasome system (UPS), known to be essential for the viability of tumor cells. The induction of oxidative stress, depletion of glutathione, and induction of high-molecular-weight (HMW) complexes have also been reported. We here examined the response of acute myeloid leukemia (AML) cells to the dienone compound VLX1570. AML cells have relatively high protein turnover rates and have also been reported to be sensitive to depletion of reduced glutathione. We found AML cells of diverse cytogenetic backgrounds to be sensitive to VLX1570, with drug exposure resulting in an accumulation of ubiquitin complexes, induction of ER stress, and the loss of cell viability in a dose-dependent manner. Caspase activation was observed but was not required for the loss of cell viability. Glutathione depletion was also observed but did not correlate to VLX1570 sensitivity. Formation of HMW complexes occurred at higher concentrations of VLX1570 than those required for the loss of cell viability and was not enhanced by glutathione depletion. To study the effect of VLX1570 we developed a zebrafish PDX model of AML and confirmed antigrowth activity in vivo. Our results show that VLX1570 induces UPS inhibition in AML cells and encourage further work in developing compounds useful for cancer therapeutics.

Rapeseed meal valorization strategies via nitrogen- and oxygen-limited production of polyhydroxyalkanoates with Pseudomonas putida.

Rapeseed meal (RSM) is a candidate for biopolymer production due to its abundance, low cost and potential integration with other rapeseed-derived products. However, existing studies pursuing such schemes are limited. The feasibility of different strategies for RSM valorization via protein extraction and polyhydroxyalkanoate production were evaluated. Nitrogen-limited RSM media was produced from hydrolysis of residues which had undergone extensive protein extraction using sodium hydroxide. A study of oxygen-limited fermentation was also performed on hydrolysate of untreated RSM via batch feeding. The typical strategy of using a high carbon-to-nitrogen ratio may not be the most suitable route for polyhydroxyalkanoate (PHA) production using nitrogen-rich biomass as a feedstock. Central composite design-based experiments show that due to mass transfer limitations protein extraction at 1-L scale could only achieve yields around 50% and 69%, at room temperature and 60 °C, respectively. Protein extraction yields reduced with successive extractions, meaning that whilst the RSM hydrolysate is viable for growth, designing a valorization scheme which has the fermentation step dictated by the protein extraction may not be practical/economical. A better route which utilizes oxygen-limitation to initially induce stationary phase was identified, giving accumulation of polyhydroxyalkanoate once the oxygen levels began to recover; 8.93% and 1.75% PHA accumulation in fed-batch cultures of synthetic and RSM media, respectively. The findings demonstrate that decoupling of protein extraction performance from PHA synthesis is feasible. This study provides important insight into the degrees of freedom available in the design of a holistic valorization scheme of rapeseed meal, and high protein lignocellulosic biomass in general.

Transradial access for diagnostic angiography and interventional neuroradiology procedures: A four-year single-center experience.

PURPOSE: The objective of this study was to assess the efficacy and safety of transradial access for diagnostic angiography and interventional neuroradiology procedures. METHODS: This was a retrospective analysis of a single-center experience based on 225 patients attended between August 2015 and October 2019, in which transradial access was used for diagnostic angiography and endovascular interventions. Ultrasound-guided access was done at the level of the forearm or anatomical or snuffbox (distal transradial access). Conventional forearm transradial access was done in 179 procedures (right, left and bilateral in 169, 5 and 5, respectively), while distal transradial access was done in 46 cases (41 right and 5 left). Primary outcome measures included successful catheterization, need to change access, or technical complications. RESULTS: In the group of 131 diagnostic angiographies, the technique success rate was 100% to target the right vertebral artery, 97% for the right internal carotid, 93.5% for the left internal carotid, 82% for the left vertebral artery, and 100% for both common and external carotid arteries. All patients were discharged within 2-4 h after the procedure. A total of 94 interventional procedures were performed, including aneurysms in 39 cases, stroke in 34, and other procedures (carotid stents, arteriovenous malformations, carotid-cavernous fistula) in the remaining 21. The overall technical success in both diagnostic angiographies and interventional procedures was 97.7%. In four cases of diagnostic angiography and in 1 intervention, it was necessary to switch from transradial access to transfemoral access. Three cases of hematoma related to the access site were recorded. CONCLUSIONS: In our experience, transradial access is an alternative approach for diagnostic angiography and neuro-interventions.

Overview of neoteric solvents as extractants in food industry: A focus on phenolic compounds separation from liquid streams.

The loss and waste of food is a matter of great concern, leading to a multifaceted problem with negative economic, social, and environmental impacts as addressed in the UN Sustainable Development Goals number 2: zero hunger. The wine, fruit juice and vegetable oil processing industries generate significant amounts of wastes and side streams containing potentially valuable bioactive compounds. Some of them are plant secondary phenolic metabolites that offer remarkable health benefits (as antioxidants and anti-inflammatory compounds). One of the current challenges is the recovery of such bioactive compounds from residual matrices for further applications in food, pharmaceutical and cosmetic industries. Within this framework and in the scope of the Green Chemistry concept, one of the current challenges is to find eco-efficient techniques for the recovery of bioactive compounds. In this context, neoteric solvents are considered a greener alternative to traditional solvents, as the latter are more harmful to human and animal health, and environment. This overview focuses on recent advances in the use of hydrophobic neoteric solvents, i.e. ionic liquids, eutectic solvents, and bio-based solvents, for liquid-liquid extraction of phenolic compounds from liquid agri-food matrices.