As a teaching subject, animal welfare is challenging for educators and learners, as was recently shown in a recent survey on the evolution of animal welfare teaching in Europe. Among several ...suggestions to overcome the current resistance to implementing animal welfare education, we highlight two. The first is that animal welfare education should be based on learner-centred approaches; the second is that it should encompass both animal welfare science and ethics and law. To the best of our knowledge, there are no learner-centred pedagogical approaches that can simultaneously explore scientific and ethical concepts. Furthermore, when exploring ethical concepts within the educational context, there is the additional challenge of being able to depart from discussion and debate to a systematic organization of knowledge. Our work simultaneously addresses these two challenges, presenting the design and implementation of a novel web-based learner-centred pedagogical platform for farm animal welfare teaching. The platform, named ANIPHI, uses the Delphi method’s iterative nature as a learning process to generate both reflection and (online) debate among learners. ANIPHI can be used by educators in an online environment, in a classroom environment, or in a combination of the two environments. ANIPHI was developed within the ERASMUS+ ANICARE project and is an open web-based platform for all educators interested in teaching farm animal welfare. Given ANIPHI’s flexible and user-friendly nature, the platform simultaneously exposes learners to ethical and scientific concepts in different educational realities, according to the educator’s objectives. Furthermore, videos depicting different husbandry practices across different types of animal production and countries are embedded in the platform. These videos are commented on by the farmer himself and by animal scientists, which enriches the learner’s experience. Educators across the ANICARE consortium have already successfully tested the ANIPHI platform for different farm animal welfare topics. We conclude this article by presenting one example of using ANIPHI in a real-life educational context, where we discuss some aspects of the design and use of our pedagogical platform.
Abstract
Several effective SARS-CoV-2 vaccines are currently in use, but effective boosters are needed to maintain or increase immunity due to waning responses and the emergence of novel variants. ...Here we report that intranasal vaccinations with adenovirus 5 and 19a vectored vaccines following a systemic plasmid DNA or mRNA priming result in systemic and mucosal immunity in mice. In contrast to two intramuscular applications of an mRNA vaccine, intranasal boosts with adenoviral vectors induce high levels of mucosal IgA and lung-resident memory T cells (T
RM
); mucosal neutralization of virus variants of concern is also enhanced. The mRNA prime provokes a comprehensive T cell response consisting of circulating and lung T
RM
after the boost, while the plasmid DNA prime induces mostly mucosal T cells. Concomitantly, the intranasal boost strategies lead to complete protection against a SARS-CoV-2 infection in mice. Our data thus suggest that mucosal booster immunizations after mRNA priming is a promising approach to establish mucosal immunity in addition to systemic responses.
Airway epithelial cells contribute to a variety of lung diseases including allergic asthma, where IL‐4 and IL‐13 promote activation of the transcription factor STAT6. This leads to goblet cell ...hyperplasia and the secretion of effector molecules by epithelial cells. However, the specific effect of activated STAT6 in lung epithelial cells is only partially understood. Here, we created a mouse strain to selectively investigate the role of constitutively active STAT6 in Club cells, a subpopulation of airway epithelial cells. CCSP‐Cre_STAT6vt mice and bronchiolar organoids derived from these show an enhanced expression of the chitinase‐like protein Chil4 (Ym2) and resistin‐like molecules (Relm‐α, ‐β, ‐γ). In addition, goblet cells of these mice spontaneously secrete mucus into the bronchi. However, the activated epithelium resulted neither in impaired lung function nor conferred a protective effect against the migrating helminth Nippostrongylus brasiliensis. Moreover, CCSP‐Cre_STAT6vt mice showed similar allergic airway inflammation induced by live conidia of the fungus Aspergillus fumigatus and similar recovery after influenza A virus infection compared to control mice. Together these results highlight that STAT6 signaling in Club cells induces the secretion of Relm proteins and mucus without impairing lung function, but this is not sufficient to confer protection against helminth or viral infections.
The selective overexpression of constitutively activated STAT6vt in lung Club cells results in enhanced mucus production and expression of the resistin‐like molecule alpha. This alteration shows no impact on eosinophil recruitment, N. brasiliensis infection, A. fumigatus induced allergic airway inflammation, or influenza A virus infection.
PREMISE
Flowering plants with poricidal anthers are commonly visited by buzzing bees, which vibrate flowers to extract pollen. However, not all flower visitors are in fact pollinators, and features ...such as body size and duration of flower visits are important factors in determining pollination effectiveness. We tested whether bee‐to‐flower size relationships predict the pollination effectiveness of flower visitors of a buzz‐pollinated species (Chamaecrista ramosa, Fabaceae).
METHODS
We sorted 13 bee taxa into three groups: smaller than, equivalent to (“fit‐size”), and larger than flower herkogamy (spatial separation between anthers and stigma). We expected the latter two groups to touch the stigmas, which would be an indicator of pollination effectiveness, more frequently than the first group. To test this hypothesis, we assessed contact with stigmas, foraging behavior, and duration of visits for the three size groups of bees.
RESULTS
Our data reveal that small bees scarcely touched the stigmas, while large and fit‐size bees were the most efficient pollinators, achieving high stigma‐touching rates, conducting much shorter flower visits, and visiting flowers and conspecific plants at high rates during foraging bouts.
CONCLUSIONS
The results did not show size‐matching among bees and flowers, as expected, but rather a minimum size threshold of efficient pollinators. The finding of such a threshold is a nonarbitrary approach to predicting pollination effectiveness of visitors to herkogamous flowers with poricidal anthers.
Implementation and uptake of health technology assessment for evaluating medical devices require including aspects that different stakeholders consider relevant, beyond cost and effectiveness. ...However, the involvement of stakeholders in sharing their views still needs to be improved.
This article explores the relevance of distinct value aspects for evaluating different types of medical devices according to stakeholders' views.
Thirty-four value aspects collected through literature review and expert validation were the input for a 2-round Web-Delphi process. In the Web-Delphi, a panel of participants from five stakeholders' groups (healthcare professionals, buyers and policymakers, academics, industry, and patients and citizens) judged the relevance of each aspect, by assigning a relevance-level ('Critical', 'Fundamental', 'Complementary', or 'Irrelevant'), for two types of medical devices separately: 'Implantable' and 'In vitro tests based on biomarkers'. Opinions were analysed at the panel and group level, and similarities across devices were identified.
One hundred thirty-four participants completed the process. No aspects were considered 'Irrelevant', neither for the panel nor for stakeholder groups, in both types of devices. The panel considered effectiveness and safety-related aspects 'Critical' (e.g., 'Adverse events for the patient'), and costs-related aspects 'Fundamental' (e.g., 'Cost of the medical device'). Several additional aspects not included in existing frameworks' literature, e.g., related to environmental impact and devices' usage by the healthcare professional, were deemed as relevant by the panel. A moderate to substantial agreement across and within groups was observed.
Different stakeholders agree on the relevance of including multiple aspects in medical devices' evaluation. This study produces key information to inform the development of frameworks for valuing medical devices, and to guide evidence collection.
Caffeic acid (CA) is a phenolic compound synthesized by all plant species and is present in foods such as coffee, wine, tea, and popular medicines such as propolis. This phenolic acid and its ...derivatives have antioxidant, anti-inflammatory and anticarcinogenic activity.
and
studies have demonstrated the anticarcinogenic activity of this compound against an important type of cancer, hepatocarcinoma (HCC), considered to be of high incidence, highly aggressive and causing considerable mortality across the world. The anticancer properties of CA are associated with its antioxidant and pro-oxidant capacity, attributed to its chemical structure that has free phenolic hydroxyls, the number and position of OH in the catechol group and the double bond in the carbonic chain. Pharmacokinetic studies indicate that this compound is hydrolyzed by the microflora of colonies and metabolized mainly in the intestinal mucosa through phase II enzymes, submitted to conjugation and methylation processes, forming sulphated, glucuronic and/or methylated conjugates by the action of sulfotransferases, UDP-glucotransferases, and o-methyltransferases, respectively. The transmembrane flux of CA in intestinal cells occurs through active transport mediated by monocarboxylic acid carriers. CA can act by preventing the production of ROS (reactive oxygen species), inducing DNA oxidation of cancer cells, as well as reducing tumor cell angiogenesis, blocking STATS (transcription factor and signal translation 3) and suppression of MMP2 and MMP-9 (collagen IV metalloproteases). Thus, this review provides an overview of the chemical and pharmacological parameters of CA and its derivatives, demonstrating its mechanism of action and pharmacokinetic aspects, as well as a critical analysis of its action in the fight against hepatocarcinoma.
Regulatory T cells (Treg) play a critical role in immune tolerance. The scarcity of Treg therapy clinical trials in humans has been largely due to the difficulty in obtaining sufficient Treg numbers. ...We performed a preclinical investigation on the potential of mesenchymal stromal cells (MSCs) to expand Treg in vitro to support future clinical trials. Human peripheral blood mononuclear cells from healthy donors were cocultured with allogeneic bone marrow‐derived MSCs expanded under xenogeneic‐free conditions. Our data show an increase in the counts and frequency of CD4+ CD25high Foxp3+ CD127low Treg cells (4‐ and 6‐fold, respectively) after a 14‐day coculture. However, natural Treg do not proliferate in coculture with MSCs. When purified conventional CD4 T cells (Tcon) are cocultured with MSCs, only cells that acquire a Treg‐like phenotype proliferate. These MSC‐induced Treg‐like cells also resemble Treg functionally, since they suppress autologous Tcon proliferation. Importantly, the DNA methylation profile of MSC‐induced Treg‐like cells more closely resembles that of natural Treg than of Tcon, indicating that this population is stable. The expression of PD‐1 is higher in Treg‐like cells than in Tcon, whereas the frequency of PDL‐1 increases in MSCs after coculture. TGF‐β levels are also significantly increased MSC cocultures. Overall, our data suggest that Treg enrichment by MSCs results from Tcon conversion into Treg‐like cells, rather than to expansion of natural Treg, possibly through mechanisms involving TGF‐β and/or PD‐1/PDL‐1 expression. This MSC‐induced Treg population closely resembles natural Treg in terms of phenotype, suppressive ability, and methylation profile.
Coculture in vitro of purified human conventional CD4 T cells (Tcon) with mesenchymal stromal cells (MSCs) induces a population of regulatory T cells (Treg). MSC‐induced Treg (iTreg) express CD25 and Foxp3, proliferate in culture, suppress Tcon proliferation such as fresh Treg, and display low levels of DNA methylation in CAMTA1, more closely resembling fresh Treg than the Tcon they arose from.
Medical applications and biotechnological advances, including magnetic resonance imaging, cell separation and detection, tissue repair, magnetic hyperthermia and drug delivery, have strongly ...benefited from employing iron oxide nanoparticles (IONPs) due to their remarkable properties, such as superparamagnetism, size and possibility of receiving a biocompatible coating. Ongoing research efforts focus on reducing drug concentration, toxicity, and other side effects, while increasing efficacy of IONPs-based treatments. This review highlights the methods of synthesis and presents the most recent reports in the literature regarding advances in drug delivery using IONPs-based systems, as well as their antimicrobial activity against different microorganisms. Furthermore, the toxicity of IONPs alone and constituting nanosystems is also addressed.
The adoption of genomic technologies in the context of hospital-based health technology assessment presents multiple practical and organizational challenges.
This study aimed to assist the Instituto ...Português de Oncologia de Lisboa Francisco Gentil (IPO Lisboa) decision makers in analyzing which acute myeloid leukemia (AML) genomic panel contracting strategies had the highest value-for-money.
A tailored, three-step approach was developed, which included: mapping clinical pathways of AML patients, building a multicriteria value model using the MACBETH approach to evaluate each genomic testing contracting strategy, and estimating the cost of each strategy through Monte Carlo simulation modeling. The value-for-money of three contracting strategies - "Standard of care (S1)," "FoundationOne Heme test (S2)," and "New diagnostic test infrastructure (S3)" - was then analyzed through strategy landscape and value-for-money graphs.
Implementing a larger gene panel (S2) and investing in a new diagnostic test infrastructure (S3) were shown to generate extra value, but also to entail extra costs in comparison with the standard of care, with the extra value being explained by making available additional genetic information that enables more personalized treatment and patient monitoring (S2 and S3), access to a broader range of clinical trials (S2), and more complete databases to potentiate research (S3).
The proposed multimethodology provided IPO Lisboa decision makers with comprehensive and insightful information regarding each strategy's value-for-money, enabling an informed discussion on whether to move from the current Strategy S1 to other competing strategies.
In an increasing search for natural products that may heal the ulcers and avoid its recurrence, limonene appears as a promising candidate.
The present study aimed to investigate the protective effect ...of limonene in ethanol-induced gastric ulcers, in addition, to investigate the involvement of antioxidant and anti-inflammatory activities, besides the modulation of gene expression.
Male Wistar rats were orally treated with vehicle (8% tween 80), carbenoxolone (100 mg/kg) or limonene (25, 50 or 100 mg/kg) and then orally received ethanol to induce gastric ulcers formation.
The activity of myeloperoxidase (MPO) was measured. Levels of glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase (SOD) were measured. We investigated the anti-inflammatory effect of limonene measuring the levels of pro-inflammatory cytokines tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1β (IL-1β) and anti-inflammatory cytokine interleukin-10 (IL-10) by ELISA. Additionally, we investigate through real-time PCR (qPCR) the gene expression of nuclear factor-kappa B (Nf-κb), Gpx, Il-1β, Mpo, and Il-10.
Our results showed that limonene 50 mg/kg was the lowest effective dose, offering 93% of reduction in gastric ulcer area compared with the vehicle. There was an increase in mucus production and higher preservation of gastric mucosa integrity after treatment with limonene.There was a reduction in the MPO activity, a biomarker of neutrophils infiltration, and an increase in GPx activity, suggesting an antioxidant effect. Limonene displayed anti-inflammatory activity through decreasing the levels of TNF-a, IL-6, and IL-1β and increasing the level of IL-10. Limonene could down-regulate the expression of Nf-κb, Il-1β, and Mpo and up-regulate the expression of Gpx.
Our results demonstrate that oral treatment with limonene exerts gastroprotection through local mucosal defense mechanisms, such as increasing the mucus production, modulation of the oxidative stress and inflammatory response and inhibition of Nf-κb expression.
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