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.

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.

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.

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.

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.

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.

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.

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.

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.

Neuroprognostication in the Post Cardiac Arrest Patient: A Canadian Cardiovascular Society Position Statement.

Cardiac arrest (CA) is associated with a low rate of survival with favourable neurologic recovery. The most common mechanism of death after successful resuscitation from CA is withdrawal of life-sustaining measures on the basis of perceived poor neurologic prognosis due to underlying hypoxic-ischemic brain injury. Neuroprognostication is an important component of the care pathway for CA patients admitted to hospital but is complex, challenging, and often guided by limited evidence. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to evaluate the evidence underlying factors or diagnostic modalities available to determine prognosis, recommendations were generated in the following domains: (1) circumstances immediately after CA; (2) focused neurologic exam; (3) myoclonus and seizures; (4) serum biomarkers; (5) neuroimaging; (6) neurophysiologic testing; and (7) multimodal neuroprognostication. This position statement aims to serve as a practical guide to enhance in-hospital care of CA patients and emphasizes the adoption of a systematic, multimodal approach to neuroprognostication. It also highlights evidence gaps.

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.

Evaluation of Olive Leaf Phenolic Compounds' Gastrointestinal Stability Based on Co-Administration and Microencapsulation with Non-Digestible Carbohydrates.

The large generation of olive by-products has motivated their revalorization into high-added-value products. In this regard, olive leaves pose as an interesting source of bioactive compounds, due to their phenolic content with commonly known antioxidant, anti-inflammatory, and immunomodulatory properties, with potential application in non-communicable diseases. However, their effectiveness and applicability into functional foods is limited by their instability under gastrointestinal conditions. Thus, the development of protective formulations is essential. In this study, the spray-drying encapsulation of a phenolic-rich olive leaf extract with inulin as the encapsulating agent was optimized. Then, the behavior of the free extract under gastrointestinal conditions, its co-administration with the encapsulating agent, and the optimized microencapsulated formulation were studied through an in vitro gastrointestinal digestion process following the INFOGEST protocol. Digestion of the free extract resulted in the degradation of most compounds, whereas this was minimized in the co-administration of the non-encapsulated extract with the encapsulating agent. This protective effect, related to its interaction with inulin, was similar to the microencapsulated formulation. Thus, both approaches, co-administration and microencapsulation with inulin, could be promising strategies for the improvement of the stability of these anti-inflammatory and immunomodulatory compounds under gastrointestinal conditions, enhancing their beneficial effect.

Potential Antioxidant and Antiviral Activities of Hydroethanolic Extracts of Selected Lamiaceae Species.

Medicinal and aromatic plants (MAPs) are potential sources of natural bioactive phytochemical compounds of an incredible worth for the food industry, such as polyphenols. Lamiaceae medicinal and aromatic plants from Granada's high plateau, concretely Origanum bastetanum, Thymus zygis gracilis, Thymus longiflorus, Thymus membranaceus and Ziziphora hispanica, were evaluated under different conventional solid-liquid extraction conditions to obtain extracts enriched in bioactive compounds. Phenolic profile was detected by HPLC-QTOF-MS, identifying a high abundance of bioactive constituents. Furthermore, antioxidant and antiviral activities of the mentioned plants were studied as biological properties of interest for the improvement of food shelf-life. Thus, Origanum bastetanum showed the highest antioxidant potential for all assays. Antiviral activity was also tested against some important foodborne viruses, feline calicivirus (FCV), murine norovirus (MNV) and hepatitis A virus (HAV), with the highest activity obtained for Ziziphora hispanica, Thymus longiflorus and Origanum bastetanum. This research proposes the studied plants as rich sources of bioactive compounds with potential use as preservatives in the food industry.

Families' experiences of central-line infection in children: a qualitative study.

OBJECTIVE: Central venous access devices (CVADs), often known as central lines, are important for delivering medically complex care in children, and are increasingly used for children living at home. Central line-associated bloodstream infection (CLABSI) is a serious, life-threatening complication. Although the physical consequences of CLABSIs are well documented, families' views and experiences of CLABSI are poorly understood. DESIGN: Qualitative study using semistructured interviews with participants from 11 families of a child living at home with a CVAD. PARTICIPANTS: Parents of children aged 4-12 years living at home with a CVAD. Four fathers and nine mothers participated in interviews. RESULTS: The risk of CLABSI is a constant fear for families of a child with a CVAD. Though avoiding infection is a key priority for families, it is not the only one: maintaining a sense of 'normal life' is another goal. Infection prevention and control require much work and expertise on the part of families, contributing significantly to families' physical and emotional workload. CONCLUSIONS: Living with the risk of CLABSI poses additional burdens that impact on the physical and emotional well-being of families. Services to better support families to manage these burdens are needed.

The impact of the COVID-19 pandemic on the research activity and working experience of clinical academics, with a focus on gender and ethnicity: a qualitative study in the UK.

OBJECTIVE: To investigate the impact of the COVID-19 pandemic on the research activity and working experience of clinical academics, with a focus on gender and ethnicity. DESIGN: Qualitative study based on interviews and audio/written diary data. SETTING: UK study within clinical academia. PARTICIPANTS: Purposive sample of 82 clinical academics working in medicine and dentistry across all career stages ranging from academic clinical fellows and doctoral candidates to professors. METHODS: Qualitative semistructured interviews (n=68) and audio diary data (n=30; including 16 participants who were also interviewed) collected over an 8-month period (January-September 2020), thematically analysed. RESULTS: 20 of 30 (66.6%) audio diary contributors and 40 of 68 (58.8%) interview participants were female. Of the participants who disclosed ethnicity, 5 of 29 (17.2%) audio diary contributors and 19/66 (28.8%) interview participants identified as Black, Asian or another minority (BAME). Four major themes were identified in relation to the initial impact of COVID-19 on clinical academics: opportunities, barriers, personal characteristics and social identity, and fears and uncertainty. COVID-19 presented opportunities for new avenues of research. Barriers included access to resources to conduct research and the increasing teaching demands. One of the most prominent subthemes within 'personal characteristics' was that of the perceived negative impact of the pandemic on the work of female clinical academics. This was attributed to inequalities experienced in relation to childcare provision and research capacity. Participants described differential experiences based upon their gender and ethnicity, noting intersectional identities. CONCLUSIONS: While there have been some positives afforded to clinical academics, particularly for new avenues of research, COVID-19 has negatively impacted workload, future career intentions and mental health. BAME academics were particularly fearful due to the differential impact on health. Our study elucidates the direct and systemic discrimination that creates barriers to women's career trajectories in clinical academia. A flexible, strategic response that supports clinical academics in resuming their training and research is required. Interventions are needed to mitigate the potential lasting impact on capacity from the pandemic, and the potential for the loss of women from this valuable workforce.

Predictive value of immune-related adverse events during pembrolizumab treatment in non-small cell lung cancer.

OBJECTIVES: Several studies have reported the role of immune-related adverse events as a predictor of clinical benefit, but few have properly described these findings in advanced or metastatic non-small cell lung cancer treated with pembrolizumab. This study aimed to evaluate the association between immune-related adverse events development and clinical outcomes in the aforementioned group of patients. METHODS: We conducted a retrospective study in patients with advanced or metastatic non-small cell lung cancer treated with pembrolizumab. Overall response rate, progression-free survival and overall survival were evaluated according to the appearance, subtype and number of immune-related adverse events developed. We report the results of the immune-related adverse events analysis and the potential correlation between immune-related adverse events and clinical outcomes. Univariate and multivariate analyses were performed to evaluate this relationship. RESULTS: A total of 94 patients were analysed; 60 of them developed immune-related adverse events. Patients with immune-related adverse events had a significantly higher overall response rate compared with the non-immune-related adverse events group (34% vs 8.5%, χ2=0.005). Median progression-free survival was statistically significant in favour of patients with at least one immune-related adverse event (p=0.015). Median overall survival was not reached in patients with ≥1 immune-related adverse events, compared with 8 months (95% CI 0.6 to 15.4 months) in those without immune-related adverse events. Patients who developed ≥2 immune-related adverse events had longer median progression-free survival (11 vs 4 months, not statistically significant) and overall survival (not reached vs 11, p=0.022) compared with those with ≤1 immune-related adverse events. CONCLUSIONS: Obtained data showed that patients with immune-related adverse events occurrence had significantly better overall response rate and longer progression-free survival and overall survival. This study highlights the role of immune-related adverse events as a predictor of survival in a real-life setting.