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Background: Real-world evidence (RWE) can reinforce clinical trial evidence in health technology assessment (HTA). Objectives: Review HTA bodies’ (HTAbs) requirements for RWE, real uses, and acceptance across seven countries (Brazil, Canada, France, Germany, Italy, Spain, and the United Kingdom) and outline recommendations that may improve acceptance of RWE in efficacy/effectiveness assessments and appraisals processes. Methods: RWE requirements were summarized based on HTAbs’ guidelines. Acceptance by HTAbs was evaluated based on industry experience and case studies. Results: As of June 2022, RWE methodological guidelines were in place in three of the seven countries. HTAbs typically requested analyses based on local data sources, but the preferred study design and data sources differed. HTAbs had individual submission, assessment, and appraisal processes; some allowed early meetings for the protocol and/or results validation, though few involved external experts or medical societies to provide input to assessment and appraisal. The extent of submission, assessment, and appraisal requirements did not necessarily reflect the degree of acceptance. Conclusion: All the countries reviewed face common challenges regarding the use of RWE. Our proposals address the need to facilitate collaboration and communication with industry and regulatory agencies and the need for specific guidelines describing RWE design and criteria of acceptance throughout the assessment and appraisal processes.

IntroductionTo date, for all non-small cell lung cancer (NSCLC) cases, it is recommended to test for driver alterations to identify actionable therapeutic targets. In this light, comprehensive genomic profiling (CGP) with next generation sequencing (NGS) has progressively gained increasing importance in clinical practice. Here, with the aim of assessing the distribution and the real-world frequency of gene alterations and their correlation with patient characteristics, we present the outcomes obtained using FoundationOne (F1CDx) and FoundationLiquid CDx (F1L/F1LCDx) NGS-based profiling in a nationwide initiative for advanced NSCLC patients.MethodsF1CDx (324 genes) was used for tissue samples, and F1L (70 genes) or F1LCDx (324 genes) for liquid biopsy, aiming to explore the real-world occurrence of molecular alterations in aNSCLC and their relationship with patients’ characteristics.ResultsOverall, 232 advanced NSCLC patients from 11 Institutions were gathered [median age 63 years; never/former or current smokers 29.3/65.9%; adenocarcinoma/squamous 79.3/12.5%; F1CDx/F1L+F1LCDx 59.5/40.5%]. Alterations were found in 170 different genes. Median number of mutated genes per sample was 4 (IQR 3–6) and 2 (IQR 1–3) in the F1CDx and F1L/F1LCDx cohorts, respectively. TP53 (58%), KRAS (22%), CDKN2A/B (19%), and STK11 (17%) alterations were the most frequently detected. Actionability rates (tier I and II) were comparable: 36.2% F1CDx vs. 34% ctDNA NGS assays (29.5% and 40.9% F1L and F1LCDx, respectively). Alterations in KEAP1 were significantly associated with STK11 and KRAS, so as TP53 with RB1. Median tumor mutational burden was 6 (IQR 3–10) and was significantly higher in smokers. Median OS from metastatic diagnosis was 23 months (IQR 18.5–19.5) and significantly lower in patients harboring ≥3 gene mutations. Conditional three-year survival probabilities increased over time for patients profiled at initial diagnosis and exceeded those of individuals tested later in their clinical history after 12 months.ConclusionThis study confirms that NGS-based molecular profiling of aNSCLC on tissue or blood samples offers valuable predictive and prognostic insights.

The global sustainability policy emphasizes reusing of agri-food waste and by-products to enhance food bioactive properties. Thus, brioches were processed incorporating almond skin powder (ASP): control (CTR), without ASP addition; 5-ASP, with 5% (w/w) ASP; and 10-ASP, with 10% (w/w) ASP. Seven different brioches shapes were obtained for each recipe. Flavonoids were mainly detected in Tuono almond skin by Ultra-High Performance Liquid Chromatography coupled to High-Resolution Mass Spectrometry (UHPLC-HRMSMS), in particular, flavan-3-ol monomers. The ethanolic extract of Tuono almond skins contained polar lipids (oxylipins and phospholipids). Gas Chromatography–Mass Spectrometry (GC-MS) identified six major fatty acids, mainly oleic acid (48.01%). Photothermal degradation impact on bioactive compounds was evaluated using a first-order kinetic model. Antioxidant activity was studied using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), 2,2-diphenyl-1-picrylhydrazyl and β-carotene bleaching test. α-amylase, α-glucosidase, and lipase inhibitory effect were also tested. The acidification of the doughs was consistent across all trials. Lactic acid bacteria and yeast levels increased. Importantly, the final products were free from undesirable microorganisms. The addition of ASP led to reduced weight loss and specific volume for all seven brioche types. Furthermore, the firmness, crumb structure, and sensory profile of the final products were noticeably influenced. Tasters clearly favoured the Treccina brioches. The production of sweet leavened baked goods was carried out in triplicate in two independent experiments. The statistical model applied to the data considered the effects of brioche shape and the addition of ASP. Kinetic data revealed that the half-life extension for both total phenol and flavonoid content was observed in the 10-ASP sample (18.00382). 10-ASP sample exhibited promising ABTS radical scavenging activity, with inhibitory concentration 50% (IC50) values of 18.64 mg/mL after 9 days of photothermal degradation. Moreover, when testing 10-ASP Treccina against α-amylase and α-glucosidase, the IC50 values were 198.16 and 190.23 μg/mL, respectively, even after 9 days.

The influence of the addition of Curcuma longa (turmeric) powder to Ottobratica variety extra virgin olive oil (EVOO) by using malaxation or infusion processes to obtain flavoured virgin olive oil (FVOO) was determined. FVOO was monitored during one year of storage at room temperature in the dark. FVOO obtained malaxation process (CM) showed the lowest free acidity value, irrespective of the time of storage considered. C* values of 7.23 vs 6.38 and 6.79 were recorded for the FVOO obtained infusion process (CI) and CM FVOO, respectively. Moreover, CM exhibited the highest radical scavenging activity with IC50 values of 9.48 and 3.49 μg mL−1 at T0 in DPPH and ABTS tests, respectively. However, the addition of turmeric did not improve the bioactivity of the FVOO against key enzymes involved in metabolic syndrome. Collectively our data have demonstrated, once again, how the enrichment of EVOO with an aromatic and functional matrix such as turmeric does not always lead to an improvement in its intrinsic functional characteristics despite the fact that it may be appreciated by the consumer for its sensorial characteristics.

This study aims to examine the bioactivity of Calabrian extra virgin olive oil enriched with bergamot fruits (Citrus bergamia Risso & Poiteau) harvested in Reggio Calabria province (Italy). To extra virgin olive oil (EVOO), cv Ottobratica 10 and 20 % of fresh fruit was added during crushing of the olives and 2 % by infusion of freeze-dried bergamot (CFVOOB10, CFVOOB20 and IFVOOB samples, respectively) was added. EVOO, bergamot extract and flavoured samples (FVOOs), were analysed throughout a one-year period. Total phenol content (TPC) as well as total chlorophyll (TChlC) and total carotenoid (TCC) contents were spectrophotometrically determined. In addition, the phenolic profile wasstudied by UHPLC. Free acidity (FA), peroxide values (PV), spectrophotometric indices, α-tocopherol, colour, and antioxidant activity were also assessed. The impact of bergamot addition on lipase, α‐amylase, and α‐glucosidase was estimated. Expert panellists evaluated the influence on the sensorial attributes, and CFVOOB10 was found to be the most pleasant. CFVOOB10 also showed the lowest PV and the highest FA after the storage. CFVOOB20 showed good protection against lipid peroxidation. Generally, all the FVOOs maintained a better inhibitory activity against the key enzymes related to obesity, compared to the EVOO. Data analyses confirmed that these FVOOs should be considered to be functional with a good sensory profile.

This essay explores contemplative pedagogies in the writing center, a space the authors believe allows for practices of mindfulness, awareness, and reflection in organic ways, as writing center pedagogy focuses on the importance of the relational, flattening hierarchies, and a focus on the conversation between writer and tutor (or between writers). With a focus on the whole person, the writing center advocates for the type of contemplative pedagogy Mathieu and others have called for: "To see any problem as an opportunity to make ourselves more aware of the way we perpetuate pain and suffering in the world" (Minnix). Grounding this essay in bell hooks' framework of community, we will explore two important pedagogies to our center: intentional kindness (Boquet) and rhetoric of respect (Rousculp), and ways in which they have fostered contemplative pedagogy in the writing center during difficult and tenuous times in the current political climate.

This work aimed to evaluate the impact of enrichment processing on the quality parameters, bioactivity and sensorial aspects of Myristica fragrans (mace)-flavored olive oil storage for one year. The mace powder was added to extra virgin olive oil through two different processes: immediately after crushing the olives by mixing mace (1% weight/weight (w/w)) with the olive paste (MAVOO-M) and by adding mace to extra virgin olive oil (C) (2% w/w) (MAVOO-I). A multi-analytical approach was applied to measure the main qualitative indexes, such as the free acidity, peroxide value and ultraviolet parameters. The total phenolic and carotenoid contents (TPC and TCC, respectively) and α-tocopherol were also evaluated, as well as the sensory attributes. The radical scavenging potential was estimated by using two different in vitro tests, namely, 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH). A significant increase in the free acidity parameter was found in all the flavored oils, and particularly in the MAVOO-M (1.27% oleic acid); at the same time, this oil was the sample with the lowest peroxide value (i.e., 9.68 meqO2/kg) after 360 days of storage. At the end of the storage, an increase in L* values was found in both the MAVOO-M and -I vs. the C (43.88 and 43.02, respectively, vs. 42.62). The TCC was strongly influenced by the addition of mace, especially when the infusion process was used. In fact, after one year of storage, the TCC in the MAVOO-I resulted in ~34.7% more than the MAVOO-M. A promising DPPH radical scavenging activity was observed independently by the applied aromatization process, with IC50 values of 19.77 and 17.80 μg/mL for the MAVOO-M and MAVOO-I, respectively. However, this activity decreased during storage, and a similar trend was observed using the ABTS test. In conclusion the infusion as enrichment methodology led to more promising results in terms of functionality compared with the co-mixing one.

The present study aimed to investigate the impact on nutritional and functional properties of dried kiwifruit (Actinidia chinensis cv. Sungold) slices during conservation for 120 days in sealed containers in the dark at 25 °C. For this purpose, kiwifruits slices were dried at two different temperatures, 40 and 55 °C, for 30 and 25 h, respectively. Fresh and dried kiwi slices were analyzed for their pH, activity water, total solid soluble (TSS), color, titratable acidity, total phenols (TPC) and flavonoids content (TFC), organic acids, and radical scavenging activities. Analysis carried out on the dehydrated samples showed a good aptitude of kiwi material towards the drying process. Particularly, it has been observed that the drying treatment at low temperature helped to preserve the nutraceutical properties of the fruits. In fact, samples treated at 40 °C (KLT) showed at day 0 (T0) the highest TPC and TFC with values of 979.42 Gallic Acid Equivalents (GAE)/100 g of dried weight (dw) and 281.84 mg catechin equivalents (CTE)/100 g dw even if compared with fresh kiwi slices sample (FKF). Moreover, KLT also exhibited the highest values of antioxidant activity (1657 mmol Trolox/100 g dw). After 120 days storage, all dried samples showed a high ascorbic acid content (429–339 mg/100 g dw fruits) and only a slight variation of physicochemical parameters. Textural Parameters (hardness, springiness, cohesiveness, gumminess, and chewiness), apart from resilience results, showed significant differences between kiwifruit dried at 55 °C and at 50 °C (KLT and KHT, respectively). Color and aroma intensity were the main sensory descriptors with higher scores.

Chlorpyrifos (CPF) is a widely used organophosphate insecticide, though its excessive use causes environmental contamination, raising concerns about its adverse effects on human health. In this regard, Urtica dioica stands out as a promising candidate for counteracting chemical ‘contaminant’ toxicity thanks to its therapeutic properties. Therefore, our study aimed to investigate the potential of an Urtica dioica ethanolic extract (UDE) to mitigate chlorpyrifos-induced toxicity. Eight compounds in the Urtica dioica ethanolic extract have been identified, most of which present significant potential as antioxidant, anti-inflammatory, and neuroprotective agents. Chlorpyrifos exposure altered hatching rates, increased the incidence of teratogenic effects, and upregulated the expression of brain-derived neurotrophic factor (Bdnf) in zebrafish larvae telencephalon. On the other hand, UDE demonstrated a preventive effect against CPF-induced teratogenicity, which is expressed by a lower morphological deformity rate. Moreover, the UDE showed a rather protective effect, maintaining the physiological condition of the telencephalon. Additionally, CPF altered the locomotor behavior of larvae, which was characterized by irregular swimming and increased activity. This defective behavioral pattern was slightly attenuated by the UDE. Our findings suggest that the UDE possesses significant protective properties against CPF-induced toxicity, probably conferred by its natural antioxidant and anti-inflammatory contents. Still, further research is needed to elucidate the recruited mechanisms and implicated pathways on UDE’s protective effects.

Lavandula angustifolia Mill. (lavender) is one of the most used medicinal plants. Herein, we chemically characterised and investigated the antioxidant properties and the capability to inhibit key enzymes for the treatment of type 2 diabetes (TD2) and obesity such as pancreatic lipase, α-glucosidase, and α-amylase of the ethanolic extract of two lavender samples (La1 and La2) from southern Italy. Both extracts significantly inhibited α-glucosidase, while La1 inhibited α-amylase and lipase more effectively than La2. To investigate whether these properties could be due to a direct interaction of the main constituents of the extracts with the targeted enzymes, molecular docking studies have been performed. As a result, the selected compounds were able to interact with the key residues of the binding site of the three proteins, thus supporting biological data. Current findings indicate the new potential of lavender ethanolic extract for the development of novel agents for T2D and obesity.

bell hooks writes on the necessity of visionary thinking for feminist activist movements in many of her texts, one important text being Talking Back: Thinking Feminist, Thinking Black. In this [...]

Objectives: As part of an evaluation of an oral healthcare practice-based model that identifies patients with prediabetes or type-2 diabetes (T2D), this study reports on the experiences and opinions of oral health professionals and patients on the screening program. Methodology: Urban and rural oral healthcare practices were invited to participate. Participating practices invited eligible patients to participate in the screening program. Patients were categorised as low, intermediate, or high-risk for prediabetes/T2D. Patients in the intermediate or high-risk category were referred to their general practitioner (GP) for further investigation. Post-screening surveys were used to assess acceptability, barriers and facilitators of the screening program among participating oral health professionals (OHP) and patients. Results: The post-screening survey was completed by 135 patient, and 38 OHPs (i.e., dentists, dental hygienists, oral health therapists). the majority of OHPs (94.6%) who delivered the protocol were satisfied with the approach. Most patients reported satisfaction with the approach (73.2%) and would recommend it to others. Several barriers for implementation were identified by OHPs and patients. Conclusion: OHPs feedback indicated that the screening model was generally acceptable. The feedback from patients following their participation in this study was overwhelmingly positive, indicating that the screening protocols were accepted by patients.

Background: This study assesses the long-term cost-effectiveness of this screening protocol from a healthcare system perspective. Methods: Australians presenting to private oral healthcare practices recruited to the iDENTify study were included as the study population. A Markov model preceded by a decision tree was developed to assess the intervention’s long-term cost-effectiveness when rolled out to all eligible Australians, and measured against ‘no-intervention’ current practice. The model consisted of four health states: normoglycaemia; pre-diabetes; type 2 diabetes and death. Intervention reach of various levels (10%, 20%, 30%, and 40%) were assessed. The model adopted a 30-year lifetime horizon and a 2020 reference year. Costs and benefits were discounted at 5% per annum. Results: If the intervention reached a minimum of 10% of the target population, over the lifetime time horizon, each screened participant would incur a cost of $38,462 and a gain of 10.564 QALYs, compared to $38,469 and 10.561 QALYs for each participant under current practice. Screening was associated with lower costs and higher benefits (a saving of $8 per person and 0.003 QALYs gained), compared to current standard practice without such screening. Between 8 and 34 type 2 diabetes cases would be avoided per 10,000 patients screened if the intervention were taken up by 10% to 40% of private oral healthcare practices. Sensitivity analyses showed consistent results. Conclusions: Implementing type 2 diabetes screening in the private oral healthcare setting using a simple risk assessment tool was demonstrated to be cost-saving. The wider adoption of such screening is recommended.

During the last decades, the consumption of bamboo sprouts (Phyllostacys edulis) has increased because they are considered a “superfood”. However, this product is characterized by a short shelf life due to the deterioration in quality parameters. The aim of this study was to investigate the application of two modified atmosphere packaging (MAP) systems (MAP1: 2% O2, 5% CO2, 93% N2 and MAP2: 3% O2, 7% CO2, 90% N2) to fresh-shelled ready-to-eat bamboo sprouts and compare these packaging systems with vacuum packaging during storage for 28 days at 4 °C using heat-sealable polyamide and polyethylene (PA/PE) trays. Several chemical-physical parameters (moisture content, water activity, pH, headspace composition, and firmness) were monitored, as well as CIELab colorimetric parameters and microbial growth. The quantification of selected organic acids was performed via UHPLC. Mathematical kinetic models were applied to study the evolution of total phenol (TPC), flavonoid (TFC), and carotenoid content (TCC) during storage. The evolution of antioxidant potential investigated by ABTS, DPPH, and β-carotene bleaching tests was also assessed. Results showed that at the end of the storage period, significant variations in the colorimetric parameters are detectable between the sprouts apical portion and the basal one, regardless of both applied MAPs. A linear reduction in both DPPH and ABTS radical scavenging activity was evidenced during storage, regardless of the type of packaging applied. In DPPH test samples packaged in MAP after 28 days of storage, they retain good antioxidant activity, whereas in vacuum, this activity is reduced by 50% compared to the initial value (IC50 values from 24.77 to 32.74 μg/mL and from 24.77 to 71.12 μg/mL for MAP2 and vacuum, respectively).

Swallowing of foreign bodies (FB), and sensation of such in the throat, is a common complaint in the emergency department setting, with roughly 80,000 visits in 2010 for FB ingestion.1 Grill wire brushes are a rarely reported, accidental FB ingestion, although recent literature suggests that it is more common than initially thought.2 This is a report of a female with acute onset odynophagia after a meal, with a normal laryngoscopic exam that used flexible fiberoptics. Evidence of a metallic linear density was present in the retropharynx on computed tomography imaging, most consistent with a wire from a grill wire brush.

Abstract Background As part of an evaluation of an oral healthcare practice-based model that identifies patients with prediabetes or type-2 diabetes, this study reports on the proportion of patients identified with clinically confirmed type-2 diabetes (T2D)/prediabetes and barriers of implementation of the model. Methodology Urban and rural oral healthcare practices were invited to participate. Participating practices invited eligible patients to participate in the screening program using the Australian Type-2 Diabetes Risk Assessment Tool (AUSDRISK). Participants were categorised as low, intermediate, or high-risk for prediabetes/T2D. Patients in the intermediate or high-risk category were referred to their General Medical Practitioner (GP) for further investigation. Results Fifty-one oral healthcare practices and 76 Oral Health Professionals (OHP) participated (60 Dentists, 8 Dental Hygienists, 8 Oral Health Therapists). 797 patients were screened; 102 were low-risk; 331 intermediate-risk; and 364 high-risk for T2D. Of the 695 participants in the intermediate or high-risk groups, 386 (55.5%) were referred to their GP for T2D assessment. Of them, 96 (25.0%) results were returned to OHPs. Of the returned results, six were (6.3%) diagnosed with pre-T2D. Conclusion Patients found to have undiagnosed T2D/prediabetes (6.3%) were within the expected range reported in the literature. Findings indicate that identifying individuals at an elevated risk of having or developing T2D is effective, feasible and could be incorporated into oral healthcare settings. However, this integration may require additional OHPs training and education to ensure that patients at elevated risk of T2D are referred for further assessment.