Pembrolizumab-induced agranulocytosis.

INTRODUCTION: With the widespread use of anti-programmed death-1 monoclonal antibodies, such as pembrolizumab, rare side effects appear in clinical practice. CASE REPORT: We report the case of a man diagnosed with non-keratinizing squamous lung carcinoma stage IVB with programmed death-ligand 1 70% who developed agranulocytosis 10 days after a single dose of pembrolizumab as monotherapy. MANAGEMENT AND OUTCOME: Pembrolizumab was discontinued immediately. Grade 4 neutrophil decrease is mentioned in the product information sheet as a rare side effect. The patient was admitted in poor physical condition with grade 4 neutropenic fever, mucositis and anemia. Agranulocytosis did not improve despite treatment with granulocyte colony-stimulating factor, intravenous corticosteroids and intravenous immunoglobulins. He experienced a rapid worsening and died 3 weeks after admission. The causal relationship between pembrolizumab and the appearance of agranulocytosis was determined as possible according to Naranjo's modified Karch and Lasagna's imputability algorithm. DISCUSSION: Hematologic immune-related adverse events are uncommon but important side effects among patients treated with immune checkpoint inhibitors. Agranulocytosis and neutropenia are infrequently reported but can be life-threatening. The main approach for agranulocytosis consists of intravenous corticosteroids, granulocyte colony-stimulating factors and blood products. Depending on bone marrow characteristics, treatments for refractory patients include intravenous immunoglobulins or cyclosporine. After an immune-related adverse event, benefits and risks must be considered before continuation with an immune checkpoint inhibitor. Detection and communication of adverse drug reactions to the Pharmacovigilance Systems have special relevance for rare side effects.

Targeted temperature management in patients with intracerebral haemorrhage, subarachnoid haemorrhage, or acute ischaemic stroke: updated consensus guideline recommendations by the Neuroprotective Therapy Consensus Review (NTCR) group.

BACKGROUND: There is a lack of consistent, evidence-based guidelines for the management of patients with fever after brain injury. The aim was to update previously published consensus recommendations on targeted temperature management after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require admission to critical care. METHODS: A modified Delphi consensus, the Neuroprotective Therapy Consensus Review (NTCR), included 19 international neuro-intensive care experts with a subspecialty interest in the acute management of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke. An online, anonymised survey was completed ahead of the meeting before the group came together to consolidate consensus and finalise recommendations on targeted temperature management. A threshold of ≥80% for consensus was set for all statements. RESULTS: Recommendations were formulated based on existing evidence, literature review, and consensus. After intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require critical care admission, core temperature should ideally be monitored continuously and maintained between 36.0°C and 37.5°C using automated feedback-controlled devices, where possible. Targeted temperature management should be commenced within 1 h of first fever identification with appropriate diagnosis and treatment of infection, maintained for as long as the brain remains at risk of secondary injury, and rewarming should be controlled. Shivering should be monitored and managed to limit risk of secondary injury. Following a single protocol for targeted temperature management across intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke is desirable. CONCLUSIONS: Based on a modified Delphi expert consensus process, these guidelines aim to improve the quality of targeted temperature management for patients after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in critical care, highlighting the need for further research to improve clinical guidelines in this setting.

Severe hepatotoxicity during treatment with capmatinib.

INTRODUCTION: Capmatinib is a mesenchymal-epithelial transition (MET) inhibitor authorized for metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutation treatment in adult patients. CASE REPORT: We report a case of an elderly female with a diagnosis of metastatic NSCLC with MET exon 14 skipping mutation who developed a severe hepatotoxicity after 7 weeks under treatment with capmatinib. MANAGEMENT & OUTCOME: Capmatinib was immediately discontinued. Hepatotoxicity is included as "warning and precautions" in the product information sheet. The patient was admitted with severe acute hepatitis, secondary hypocoagulability and acute deterioration of renal function. She experienced a rapid worsening with a fatal outcome three days after admission. The causal relationship between capmatinib and the appearance of hepatotoxicity was determined as probable according to Naranjo's modified Karch and Lasagna's imputability algorithm. DISCUSSION: The recognition and diagnosis of drug-induced liver injury (DILI) are often difficult and delayed. Molecularly targeted agents require careful assessment of liver function both prior to and during therapy. Capmatinib hepatotoxicity is an infrequent but severe adverse drug reaction (ADR). Prescribing information includes recommendations about liver function monitoring. The main approachment for DILI is the removal of the causative agent. Detection and communication of ADRs to the Pharmacovigilance Systems have special relevance for novel drugs, with little data in real life setting.

Engineering a defined culture medium to grow Piscirickettsia salmonis for its use in vaccine formulations.

Piscirickettsia salmonis is a facultative Gram-negative intracellular bacterium that produces piscirickettsiosis, disease that causes a high negative impact in salmonid cultures. The so-far-unidentified nutritional requirements have hindered its axenic culture at laboratory and industrial scales for the formulation of vaccines. The present study describes the development of a defined culture medium for P. salmonis. The culture medium was formulated through rational design involving auxotrophy test and statistical designs of experiments, considering the genome-scale metabolic reconstruction of P. salmonis reported by our group. The whole optimization process allowed for a twofold increase in biomass and a reduction of about 50% of the amino acids added to the culture medium. The final culture medium contains twelve amino acids, where glutamic acid, threonine and arginine were the main carbon and energy sources, supporting 1.65 g/L of biomass using 6.5 g/L of amino acids in the formulation. These results will contribute significantly to the development of new operational strategies to culture this bacterium for the production of vaccines.

Imaging for Neuroprognostication After Cardiac Arrest: Systematic Review and Meta-analysis.

BACKGROUND: Predicting neurological outcome in comatose survivors of cardiac arrest relies on clinical findings, radiological and neurophysiological test results. To evaluate the predictive accuracy of brain computed tomography (CT) and magnetic resonance imaging (MRI) for prognostication of neurological outcomes after cardiac arrest. METHODS: We searched MEDLINE (database inception to August 2018) and included all observational cohort studies or randomized controlled trials including adult (16 years or older) survivors of cardiac arrest which evaluated the diagnostic accuracy of CT or MRI for predicting neurologic outcome or mortality. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. All review stages were conducted independently by 2 reviewers, and where possible data were pooled using bivariate meta-analysis. The main outcome was to evaluate the of accuracy of CT and MRI in neuroprognostication of patients after cardiac arrest. RESULTS: We included 44 studies that examined brain CT (n = 24) or MRI (n = 21) in 4008 (n per study, 9-398) patients. Decreased grey to white matter ratio on CT (20 studies) was useful for predicting poor neurological outcome (sensitivity 0.44, 95% CI 0.29-0.60; specificity 0.97, 95% CI 0.93-0.99; positive likelihood ratio [LR+] 13.8, 95% CI 6.9-27.7). Similarly, diffusion-weighted imaging (DWI) on MRI (16 studies; sensitivity 0.77, 95% CI 0.65-0.85; specificity 0.92, 95% CI 0.85-0.96; LR+ 9.2, 95% CI 5.2-16.4) and DWI and fluid-attenuated inversion recovery (FLAIR) MRI (4 studies, sensitivity 0.70, 95% CI 0.43-0.88; specificity 0.95, 95% CI 0.79-0.99; LR+ 13.4, 95% CI 3.5-51.2) were useful for predicting poor neurological outcomes. We found marked heterogeneity in timing of radiological examinations and neurological assessments relative to the cardiac arrest. CONCLUSION: Decreased grey to white matter ratio on CT and DWI or DWI and FLAIR on MRI are useful adjuncts for predicting poor early neurological outcome after cardiac arrest.

Antiepileptic Drugs to Prevent Seizures After Spontaneous Intracerebral Hemorrhage.

Background and Purpose- We sought to evaluate the available literature to determine whether primary seizure prevention with antiepileptic drugs reduces the risk of poor outcomes and clinically relevant seizures among adult patients with spontaneous intracerebral hemorrhage. Methods- Meta-analysis of observational studies and randomized controlled trials evaluating the use of any antiepileptic drug for primary seizure prevention among adult (≥18 years) patients with spontaneous intracerebral hemorrhage. The primary end point was poor clinical outcome at the longest recorded follow-up, defined as either a high (>3) modified Rankin Scale score or all-cause mortality during follow-up if the modified Rankin Scale score was not recorded. Early and late seizures were secondary outcomes. A random mixed effects model was used to estimate the pooled odds ratio of outcomes and associated 95% CI. Results- We identified 7 studies with a total of 3241 patients for analysis of the primary outcome and 4 studies with a total of 1861 patients for analysis of the secondary outcomes. Overall, the use of antiepileptic drugs was not associated with a high Rankin Scale or all-cause mortality (odds ratio: 0.99; 95% CI, 0.66-1.49) or incident seizures (odds ratio: 0.89; 95% CI, 0.52-1.51) at the longest recorded follow-up time. Conclusions- The use of antiepileptic drugs as primary prevention among adult patients with spontaneous intracerebral hemorrhage is not associated with improved neurological function during long-term follow-up. Future studies should focus on the preventive use of distinct antiepileptic agents among patients at high risk of both seizures and poor outcomes.

El receptor soluble de insulina y el síndrome metabólico.

The metabolic syndrome describes a group of signs that increase the likelihood for developing type 2 diabetes mellitus, cardiovascular diseases and some types of cancer. The action of insulin depends on its binding to membrane receptors on its target cells. We wonder if blood insulin could travel bound to proteins and if, in the presence of hyperinsulinemia, a soluble insulin receptor might be generated. We used young adult Wistar rats (which have no predisposition to obesity or diabetes), whose drinking water was added 20 % of sugar and that were fed a standard diet ad libitum for two and six months. They were compared with control rats under the same conditions, but that had running water for consumption. At two months, the rats developed central obesity, moderate hypertension, high triglyceride levels, hyperinsulinemia, glucose intolerance and insulin resistance, i.e. metabolic syndrome. Electrophoresis of the rats' plasma proteins was performed, followed by Western Blot (WB) for insulin and for the outer portion of the insulin receptor. The bands corresponding to insulin and to the receptor external part were at the same molecular weight level, 25-fold higher than that of free insulin. We demonstrated that insulin, both in control animals and in those with hyperinsulinemia, travels bound to the receptor outer portion (ectodomain), which we called soluble insulin receptor, and that is released al higher amounts in response to plasma insulin increase; in rats with metabolic syndrome and hyperinsulinemia, plasma levels are much higher than in controls. Soluble insulin receptor increase in blood might be an early sign of metabolic syndrome.

El síndrome metabólico es un conjunto de signos que aumentan la probabilidad de desarrollar diabetes mellitus tipo 2, enfermedades cardiovasculares y algunos tipos de cáncer. La acción de la insulina depende de su unión a los receptores en la membrana de sus células diana. Para responder a la pregunta de si la insulina en la sangre podría viajar unida a proteínas y si en presencia de hiperinsulinemia podría generarse un receptor soluble de insulina, utilizamos ratas wistar (no tienen predisposición a la obesidad ni a la diabetes), adultas jóvenes, a cuya agua de consumo se adicionó 20 % de azúcar y a las que se les administró dieta estándar ad libitum, durante dos y seis meses; fueron comparadas con ratas control que tuvieron las mismas condiciones, pero con agua corriente para consumo. A los dos meses, las ratas desarrollaron obesidad central, hipertensión moderada, triglicéridos altos, hiperinsulinemia, intolerancia a la glucosa y resistencia a la insulina, es decir, síndrome metabólico. Se realizó electroforesis de las proteínas del plasma de las ratas, seguida de Western Blot para insulina y para la porción externa del receptor de insulina. Las bandas correspondientes a la insulina y la parte externa del receptor estaban al mismo nivel de peso molecular, 25 veces mayor que el de la insulina libre. Demostramos que la insulina, tanto en animales testigo como en aquellos con hiperinsulinemia, viaja unida a la porción externa del receptor (ectodominio), al cual denominamos receptor soluble de insulina, que se libera en mayor cantidad en respuesta al incremento en la insulina plasmática; en las ratas con síndrome metabólico e hiperinsulinemia, los niveles en plasma son mucho mayores que en los controles. El incremento del receptor soluble de insulina en sangre podría ser un dato temprano de síndrome metabólico.

Soluble insulin receptor and metabolic syndrome.

The metabolic syndrome describes a group of signs that increase the likelihood for developing type 2 diabetes mellitus, cardiovascular diseases and some types of cancer. The action of insulin depends on its binding to membrane receptors on its target cells. We wonder if blood insulin could travel bound to proteins and if, in the presence of hyperinsulinemia, a soluble insulin receptor might be generated. We used young adult Wistar rats (which have no predisposition to obesity or diabetes), whose drinking water was added 20 % of sugar and that were fed a standard diet ad libitum for two and six months. They were compared with control rats under the same conditions, but that had running water for consumption. At two months, the rats developed central obesity, moderate hypertension, high triglyceride levels, hyperinsulinemia, glucose intolerance and insulin resistance, i.e., metabolic syndrome. Electrophoresis of the rats' plasma proteins was performed, followed by Western Blot (WB) for insulin and for the outer portion of the insulin receptor. The bands corresponding to insulin and to the receptor external part were at the same molecular weight level, 25-fold higher than that of free insulin. We demonstrated that insulin, both in control animals and in those with hyperinsulinemia, travels bound to the receptor outer portion (ectodomain), which we called soluble insulin receptor, and that is released al higher amounts in response to plasma insulin increase; in rats with metabolic syndrome and hyperinsulinemia, plasma levels are much higher than in controls. Soluble insulin receptor increase in blood might be an early sign of metabolic syndrome.

Do Patients Feel Well Informed in a Radiation Oncology Service?

Information received by cancer patients has gained importance in recent decades. The aim of this study was to evaluate the perception of information received by oncological patients in a radiotherapy department and to measure the importance of the other information sources. A cross-sectional study was conducted, evaluating patients who received radiotherapy. All the patients were asked two questionnaires: the EORTC QLQ-INFO26 module evaluating their satisfaction with received information, and a questionnaire analyzing other sources of information search. One hundred patients between 27 and 84 years were enrolled. Breast cancer (26 %) was the commonest cancer. Patients felt better informed about the medical tests and secondly about the performed treatment. The younger patients were those who were more satisfied with the information received and patients with no formal education felt less satisfied, with statistically significant differences. Patients did not seek external information; at the most, they asked relatives and other people with cancer. Patients were satisfied with the received information, although a high percentage would like more information. In general, patients did not search for external information sources. Age and educational level seem to influence in the satisfaction with the received information.

Neuropathy-specific alterations in a Mexican population of diabetic patients.

BACKGROUND: Neuropathy is one of the major complications of type 2 diabetes mellitus. Our first aim was to determine the clinical characteristics of a population of diabetic patients with different types of neuropathy. Our next goal was to characterize the cytokine profile (IL-6 and IL-10), nerve growth factor (NGF) and circulating cell-adhesion molecules in these patients. Finally, we aimed to compare the renal function among the groups of neuropathic patients. METHODS: In a cross-sectional study, we included 217 diabetic patients classified in three groups: sensory polyneuropathy with hypoesthesia (DShP) or hyperesthesia (DSHP), and motor neuropathy (DMN). Two control groups were included: one of 26 diabetic non-neuropathic patients (DNN), and the other of 375 non-diabetic (ND) healthy subjects. The participants were attending to the Mexican Institute of Social Security. RESULTS: The circulating levels of NGF were significantly lower in diabetic patients, compared to healthy subjects. The range of IL-6 and IL-10 levels in neuropathic patients was higher than the control groups; however, several samples yielded null measurements. Neuropathic patients also showed increased circulating levels of the adhesion molecules ICAM, VCAM, and E-Selectin, compared to the ND group. Moreover, neuropathic patients showed reduced glomerular filtration rates compared to healthy subjects (82-103 ml/min per 1.73 m2, data as range from 25th-75th percentiles), especially in the group with DMN (45-76 ml/min per 1.73 m2). CONCLUSIONS: Some particular alterations in neuropathic patients included -but were not limited to- changes in circulating NGF, cell adhesion molecules, inflammation, and the worsening of the renal function. This study supports the need for further clinical surveillance and interventions considering a neuropathy-related basis.

[ANALYSIS USING AN EXPERT PANEL OF ACTIVITIES AND COMPETENCIES WHICH NURSING CLINICAL PRACTICE TUTORS IN THE COMUNIDAD AUTÓNOMA DE MADRID SHOULD POSSESS]. / Análisis mediante panel de expertos de las competencias. Y ACTIVIDADES DE LOS TUTORES DE PRÁCTICAS CLÍNICAS DE ENFERMERÍA EN LA COMUNIDAD AUTÓNOMA DE MADRID.

UNLABELLED: Although practical training has always been important in Nursing, it has reached a new dimension in the European Higher Education Area. This has involved adapting the syllabus, where one of the new features is considering clinical practice as an independent subject and also including the concept of competence as a result of the students' learning. The figure of the tutor becomes one of the key factors and therefore their activities and competencies must be defined. OBJECTIVE: To enumerate and prioritize, by agreement, the main activities and competences by the tutor of clinical practices in the Comunidad Autónoma de Madrid should posses. METHODOLOGY. Quantitative focus, analysis by group of experts between 2010 and 2013. RESULTS. A total of 510 nurses have participated, 17 panels of experts have met and consensus has been reached on 22 competencies and 12 activities. CONCLUSIONS: The description of activities and competencies can be extremely useful for selecting, evaluating and developing nursing clinical practice tutors, becoming a baseline and reducing the subjectivity in the development of tutors according to the new demands of the European Higher Education Area.

Role for the TRPV1 channel in insulin secretion from pancreatic beta cells.

Transient receptor potential channels have been put forward as regulators of insulin secretion. A role for the TRPV1 ion channel in insulin secretion has been suggested in pancreatic beta cell lines. We explored whether TRPV1 is functionally expressed in RINm5F and primary beta cells from neonate and adult rats. We examined if capsaicin could activate cationic non-selective currents. Our results show that TRPV1 channels are not functional in insulin-secreting cells, since capsaicin did not produce current activation, not even under culture conditions known to induce the expression of other ion channels in these cells. Although TRPV1 channels seem to be irrelevant for the physiology of isolated beta cells, they may play a role in glucose homeostasis acting through the nerve fibers that regulate islet function. At the physiological level, we observed that Trpv1 (-/-) mice presented lower fasting insulin levels than their wild-type littermates, however, we did not find differences between these experimental groups nor in the glucose tolerance test or in the insulin secretion. However, we did find that the Trpv1 (-/-) mice exhibited a higher insulin sensitivity compared to their wild-type counterparts. Our results demonstrate that TRPV1 does not contribute to glucose-induced insulin secretion in beta cells as was previously thought, but it is possible that it may control insulin sensitivity.

Paediatric radiotherapy in the United Kingdom: an evolving subspecialty and a paradigm for integrated teamworking in oncology.

Many different malignancies occur in children, but overall, cancer in childhood is rare. Survival rates have improved appreciably and are higher compared with most adult tumour types. Treatment schedules evolve as a result of clinical trials and are typically complex and multi-modality, with radiotherapy an integral component of many. Risk stratification in paediatric oncology is increasingly refined, resulting in a more personalized use of radiation. Every available modality of radiation delivery: simple and advanced photon techniques, proton beam therapy, molecular radiotherapy, and brachytherapy, have their place in the treatment of children's cancers. Radiotherapy is rarely the sole treatment. As local therapy, it is often given before or after surgery, so the involvement of the surgeon is critically important, particularly when brachytherapy is used. Systemic treatment is the standard of care for most paediatric tumour types, concomitant administration of chemotherapy is typical, and immunotherapy has an increasing role. Delivery of radiotherapy is not done by clinical or radiation oncologists alone; play specialists and anaesthetists are required, together with mould room staff, to ensure compliance and immobilization. The support of clinical radiologists is needed to ensure the correct interpretation of imaging for target volume delineation. Physicists and dosimetrists ensure the optimal dose distribution, minimizing exposure of organs at risk. Paediatric oncology doctors, nurses, and a range of allied health professionals are needed for the holistic wrap-around care of the child and family. Radiographers are essential at every step of the way. With increasing complexity comes a need for greater centralization of services.

Exploring the Nutritional and Bioactive Potential of Olive Leaf Residues: A Focus on Minerals and Polyphenols in the Context of Spain's Olive Oil Production.

Lyophilized plant-origin extracts are rich in highly potent antioxidant polyphenols. In order to incorporate them into food products, it is necessary to protect these phytochemicals from atmospheric factors such as heat, light, moisture, or pH, and to enhance their bioavailability due to their low solubility. To address these challenges, recent studies have focused on the development of encapsulation techniques for antioxidant compounds within polymeric structures. In this study, lyophilized olive leaf extracts were microencapsulated with the aim of overcoming the aforementioned challenges. The method used for the preparation of the studied microparticles involves external ionic gelation carried out within a water-oil (W/O) emulsion at room temperature. HPLC analysis demonstrates a high content of polyphenols, with 90% of the bioactive compounds encapsulated. Meanwhile, quantification by inductively coupled plasma optical emission spectroscopy (ICP-OES) reveals that the dried leaves, lyophilized extract, and microencapsulated form contain satisfactory levels of macro- and micro-minerals (calcium, potassium, sodium). The microencapsulation technique could be a novel strategy to harness the polyphenols and minerals of olive leaves, thus enriching food products and leveraging the antioxidant properties of the polyphenolic compounds found in the lyophilized extract.

Mastering the brain in critical conditions: an update.

Acute brain injuries, such as traumatic brain injury and ischemic and hemorragic stroke, are a leading cause of death and disability worldwide. While characterized by clearly distict primary events-vascular damage in strokes and biomechanical damage in traumatic brain injuries-they share common secondary injury mechanisms influencing long-term outcomes. Growing evidence suggests that a more personalized approach to optimize energy substrate delivery to the injured brain and prognosticate towards families could be beneficial. In this context, continuous invasive and/or non-invasive neuromonitoring, together with clinical evaluation and neuroimaging to support strategies that optimize cerebral blood flow and metabolic delivery, as well as approaches to neuroprognostication are gaining interest. Recently, the European Society of Intensive Care Medicine organized a 2-day course focused on a practical case-based clinical approach of acute brain-injured patients in different scenarios and on future perspectives to advance the management of this population. The aim of this manuscript is to update clinicians dealing with acute brain injured patients in the intensive care unit, describing current knowledge and clinical practice based on the insights presented during this course.

Association of Dietary Patterns with Cardiovascular Disease Risk Factors in Mexican Adults: Insights from a Cross-Sectional Descriptive Study.

Dietary patterns (DPs) are an essential tool to analyze the relationship between diet and health as they have presented an association with the incidence of chronic non-communicable diseases. Therefore, the aim of this study was the identification and characterization of DPs and their association with cardiovascular risk factors. For this purpose, a cross-sectional descriptive study was carried out in 165 Mexican adults, including dietary intakes derived from a validated food frequency questionnaire, clinical history, anthropometry, and biochemical biomarkers using standardized procedures for glucose, total cholesterol, triglycerides, LDL-c, and HDL-c. DPs were identified through principal component analysis and ordinal logistic regression was used to examine associations between DPs and cardiovascular disease risk factors. Three DPs were identified: Mexican Fast-Food, Variety-Food, and Healthy-Economic, with a high prevalence of overweight and obesity (78%). Having a high adherence to a Mexican Fast-Food pattern (OR 1.71 CI 1.4-2.8), being sedentary (OR 4.85 2.32-10.15) and smoking (0R 6.4 CI 2.40-16.9) increased the risk of having a high scale of risk factors (four or more risk factors simultaneously). In conclusion, the Mexican Fast-Food pattern showed an increase in the risk of having multiple risk factors, while a sedentary lifestyle and overeating were largely responsible for the prevalence of overweight and obesity in this group of Mexican adults.

Bioactive Potential of Aqueous Phenolic Extracts of Spices for Their Use in the Food Industry-A Systematic Review.

The interest on the use of natural sources in the food industry has promoted the study of plants' phenolic compounds as potential additives. However, the literature has been focusing on essential oils, with very few studies published regarding aqueous extracts, their phenolic composition, and bioactivity. A systematic review was conducted on different databases following PRISMA guidelines to evaluate the relevance of the phenolic content of different aromatic spices (oregano, rosemary, thyme, ginger, clove, and pepper), as related to their bioactivity and potential application as food additives. Although different extraction methods have been applied in the literature, the use of green approaches using ethanol and deep eutectic solvents has increased, leading to the development of products more apt for human consumption. The studied plants present an interesting phenolic profile, ranging from phenolic acids to flavonoids, establishing a correlation between their phenolic content and bioactivity. In this sense, results have proven to be very promising, presenting those extracts as having similar if not higher bioactivity than synthetic additives already in use, with associated health concerns. Nevertheless, the study of spices' phenolic extracts is somehow limited to in vitro studies. Therefore, research in food matrices is needed for more understanding of factors interfering with their preservation activity.

Extraction, Characterization, and Bioactivity of Phenolic Compounds-A Case on Hibiscus Genera.

Phenolic compounds have recently gained interest, as they have been related to improvements in health and disease prevention, such as inflammatory intestinal pathologies and obesity. However, their bioactivity may be limited by their instability or low concentration in food matrices and along the gastrointestinal tract once consumed. This has led to the study of technological processing with the aim of optimizing phenolic compounds' biological properties. In this sense, different extraction systems have been applied to vegetable sources for the purpose of obtaining enriched phenolic extracts such as PLE, MAE, SFE, and UAE. In addition, many in vitro and in vivo studies evaluating the potential mechanisms of these compounds have also been published. This review includes a case study of the Hibiscus genera as an interesting source of phenolic compounds. The main goal of this work is to describe: (a) phenolic compound extraction by designs of experiments (DoEs) applied to conventional and advanced systems; (b) the influence of the extraction system on the phenolic composition and, consequently, on the bioactive properties of these extracts; and (c) bioaccessibility and bioactivity evaluation of Hibiscus phenolic extracts. The results have pointed out that the most used DoEs were based on response surface methodologies (RSM), mainly the Box-Behnken design (BBD) and central composite design (CCD). The chemical composition of the optimized enriched extracts showed an abundance of flavonoids, as well as anthocyanins and phenolic acids. In vitro and in vivo studies have highlighted their potent bioactivity, with particular emphasis on obesity and related disorders. This scientific evidence establishes the Hibiscus genera as an interesting source of phytochemicals with demonstrated bioactive potential for the development of functional foods. Nevertheless, future investigations are needed to evaluate the recovery of the phenolic compounds of the Hibiscus genera with remarkable bioaccessibility and bioactivity.

Effect of Microwave and Ultrasound-Assisted Extraction on the Phytochemical and In Vitro Biological Properties of Willow (Salix alba) Bark Aqueous and Ethanolic Extracts.

White willow (Salix alba) is a medicinal plant used in folk medicine. In this study, aqueous and ethanolic willow bark extracts were obtained via ultrasonic-assisted extraction (UAE) and microwave-assisted extraction (MAE), and analyzed regarding their phytochemical (total phenolics, phenolic acids, flavonoids, and tannins) content and in vitro biological properties (antibacterial and antifungal activity, acetylcholinesterase AChE inhibitory activity and anti-inflammatory effects). The highest phenolic, tannin, and flavonoid contents were found for willow bark extracts obtained via microwave-assisted extraction using ethanol as a solvent (SA-ME). The polyphenol load of all MAE and UAE extracts was higher when conventional solid-liquid extraction was applied (ρ < 0.05). The antioxidant capacities were stronger for microwave-assisted ethanolic extracts, with the lowest IC50 values of 12 µg/mL for DPPH• and a value of 16 µg/mL for ABTS•+, whereas the conventional extraction had the highest IC50 values (22 µg/mL and 28 µg/mL, respectively). Willow bark extract showed antibacterial activity against Gram-positive bacteria S. aureus and P. aeruginosa. AChE inhibitory activity was dependent on the extraction method and solvent used, and the highest inhibition among samples was observed for SA-ME. Taken altogether, our findings suggest that willow (Salix alba) bark extract obtained via ethanolic microwave-assisted extraction is a phytochemical-rich resource with in vitro, anti-inflammatory, and AchE inhibitory properties and, therefore, potential multiple medicinal end-uses.

Non-Digestible Carbohydrates: Green Extraction from Food By-Products and Assessment of Their Effect on Microbiota Modulation.

The nature and composition of the waste produced by food industrial processing make its abundance and accumulation an environmental problem. Since these by-products may present a high potential for revalorization and may be used to obtain added-value compounds, the main goals of the technological advancements have been targeted at reducing the environmental impact and benefiting from the retrieval of active compounds with technological and health properties. Among the added-value substances, nondigestible carbohydrates have demonstrated promise. In addition to their well-known technological properties, they have been discovered to modify the gut microbiota and enhance immune function, including the stimulation of immune cells and the control of inflammatory reactions. Furthermore, the combination of these compounds with other substances such us phenols could improve their biological effect on different noncommunicable diseases through microbiota modulation. In order to gain insight into the implementation of this combined strategy, a broader focus concerning different aspects is needed. This review is focused on the optimized green and advanced extraction system applied to obtain added-value nondigestible carbohydrates, the combined administration with phenols and their beneficial effects on microbiota modulation intended for health and/or illness prevention, with particular emphasis on noncommunicable diseases. The isolation of nondigestible carbohydrates from by-products as well as in combination with other bioactive substances could provide an affordable and sustainable source of immunomodulatory chemicals.