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Henk Verloo,1 Céline Goulet,2 Diane Morin,3,4 Armin von Gunten51Department Nursing Sciences, University of Applied Sciences, Lausanne, Switzerland; 2Faculty of Nursing Science, University of Montreal, Montreal, QC, Canada; 3Institut Universitaire de Formation et Recherche en Soins (IUFRS), Faculty of Biology and Medicine, University of Lausanne, Lausanne University Hospital, Lausanne, Switzerland; 4Faculty of Nursing Science, Université Laval, Québec, Canada; 5Department of Psychiatry, Service Universitaire de Psychiatrie de l’Age Avancé (SUPAA), Lausanne University Hospital, Prilly, SwitzerlandBackground: Delirium and frailty – both potentially reversible geriatric syndromes – are seldom studied together, although they often occur jointly in older patients discharged from hospitals. This study aimed to explore the relationship between delirium and frailty in older adults discharged from hospitals.Methods: Of the 221 patients aged >65 years, who were invited to participate, only 114 gave their consent to participate in this study. Delirium was assessed using the confusion assessment method, in which patients were classified dichotomously as delirious or nondelirious according to its algorithm. Frailty was assessed using the Edmonton Frailty Scale, which classifies patients dichotomously as frail or nonfrail. In addition to the sociodemographic characteristics, covariates such as scores from the Mini-Mental State Examination, Instrumental Activities of Daily Living scale, and Cumulative Illness Rating Scale for Geriatrics and details regarding polymedication were collected. A multidimensional linear regression model was used for analysis.Results: Almost 20% of participants had delirium (n=22), and 76.3% were classified as frail (n=87); 31.5% of the variance in the delirium score was explained by frailty (R2=0.315). Age; polymedication; scores of the Confusion Assessment Method (CAM), instrumental activities of daily living, and Cumulative Illness Rating Scale for Geriatrics; and frailty increased the predictability of the variance of delirium by 32% to 64% (R2=0.64).Conclusion: Frailty is strongly related to delirium in older patients after discharge from the hospital.Keywords: Edmonton Frailty Scale, delirium risk factors, cognitive impairment, physical impairmentA Letter to the Editor has been received and published for this article

The lifecycle of fresh produce involves a sequence of biochemical events during their ontology, and these events are particularly significant for climacteric fruits. A high demand during ripening is observed in these plant products, which is reflected in a high rate of respiration and ethylene production. Increased respiratory demand triggers the activation of secondary pathways such as alternate oxidase, which do not experience critical increases in energy consumption in non-climacteric fruit. In addition, biochemical events produced by external factors lead to compensatory responses in fresh produce to counteract the oxidative stress caused by the former. The dynamics of these responses are accompanied by signaling, where reactive oxygen species play a pivotal role in fresh product cell perception. This review aims to describe the protection mechanisms of fresh produce against environmental challenges and how controlled doses of abiotic stressors can be used to improve quality and prolong their shelf-life through the interaction of stress and defense mechanisms.

Abstract Background Studies reported unintended pleiotropic effects for a number of pesticidal proteins ectopically expressed in transgenic crops, but the nature and significance of such effects in planta remain poorly understood. Here we assessed the effects of corn cystatin II (CCII), a potent inhibitor of C1A cysteine (Cys) proteases considered for insect and pathogen control, on the leaf proteome and pathogen resistance status of potato lines constitutively expressing this protein. Results The leaf proteome of lines accumulating CCII at different levels was resolved by 2-dimensional gel electrophoresis and compared with the leaf proteome of a control (parental) line. Out of ca. 700 proteins monitored on 2-D gels, 23 were significantly up- or downregulated in CCII-expressing leaves, including 14 proteins detected de novo or up-regulated by more than five-fold compared to the control. Most up-regulated proteins were abiotic or biotic stress-responsive proteins, including different secretory peroxidases, wound inducible protease inhibitors and pathogenesis-related proteins. Accordingly, infection of leaf tissues by the fungal necrotroph Botryris cinerea was prevented in CCII-expressing plants, despite a null impact of CCII on growth of this pathogen and the absence of extracellular Cys protease targets for the inhibitor. Conclusions These data point to the onset of pleiotropic effects altering the leaf proteome in transgenic plants expressing recombinant protease inhibitors. They also show the potential of these proteins as ectopic modulators of stress responses in planta, useful to engineer biotic or abiotic stress tolerance in crop plants of economic significance.

Abstract Background Skin-to-skin contact, or kangaroo mother care (KMC) has been shown to be efficacious in diminishing pain response to heel lance in full term and moderately preterm neonates. The purpose of this study was to determine if KMC would also be efficacious in very preterm neonates. Methods Preterm neonates (n = 61) between 28 0/7 and 31 6/7 weeks gestational age in three Level III NICU's in Canada comprised the sample. A single-blind randomized crossover design was employed. In the experimental condition, the infant was held in KMC for 15 minutes prior to and throughout heel lance procedure. In the control condition, the infant was in prone position swaddled in a blanket in the incubator. The primary outcome was the Premature Infant Pain Profile (PIPP), which is comprised of three facial actions, maximum heart rate, minimum oxygen saturation levels from baseline in 30-second blocks from heel lance. The secondary outcome was time to recover, defined as heart rate return to baseline. Continuous video, heart rate and oxygen saturation monitoring were recorded with event markers during the procedure and were subsequently analyzed. Repeated measures analysis-of-variance was employed to generate results. Results PIPP scores at 90 seconds post lance were significantly lower in the KMC condition (8.871 (95%CI 7.852–9.889) versus 10.677 (95%CI 9.563–11.792) p < .001) and non-significant mean differences ranging from 1.2 to1.8. favoring KMC condition at 30, 60 and 120 seconds. Time to recovery was significantly shorter, by a minute(123 seconds (95%CI 103–142) versus 193 seconds (95%CI 158–227). Facial actions were highly significantly lower across all points in time reaching a two-fold difference by 120 seconds post-lance and heart rate was significantly lower across the first 90 seconds in the KMC condition. Conclusion Very preterm neonates appear to have endogenous mechanisms elicited through skin-to-skin maternal contact that decrease pain response, but not as powerfully as in older preterm neonates. The shorter recovery time in KMC is clinically important in helping maintain homeostasis. Trial Registration (Current Controlled Trials) ISRCTN63551708

Background: Skin-to-skin contact, or kangaroo mother care (KMC) has been shown to be efficacious in diminishing pain response to heel lance in full term and moderately preterm neonates. The purpose of this study was to determine if KMC would also be efficacious in very preterm neonates.Methods: Preterm neonates (n = 61) between 28 0/7 and 31 6/7 weeks gestational age in three Level III NICU's in Canada comprised the sample. A single-blind randomized crossover design was employed. In the experimental condition, the infant was held in KMC for 15 minutes prior to and throughout heel lance procedure. In the control condition, the infant was in prone position swaddled in a blanket in the incubator. The primary outcome was the Premature Infant Pain Profile (PIPP), which is comprised of three facial actions, maximum heart rate, minimum oxygen saturation levels from baseline in 30-second blocks from heel lance. The secondary outcome was time to recover, defined as heart rate return to baseline. Continuous video, heart rate and oxygen saturation monitoring were recorded with event markers during the procedure and were subsequently analyzed. Repeated measures analysis-of-variance was employed to generate results.Results: PIPP scores at 90 seconds post lance were significantly lower in the KMC condition (8.871 (95%CI 7.852-9.889) versus 10.677 (95%CI 9.563-11.792) p < .001) and non-significant mean differences ranging from 1.2 to1.8. favoring KMC condition at 30, 60 and 120 seconds. Time to recovery was significantly shorter, by a minute(123 seconds (95%CI 103-142) versus 193 seconds (95%CI 158-227). Facial actions were highly significantly lower across all points in time reaching a two-fold difference by 120 seconds post-lance and heart rate was significantly lower across the first 90 seconds in the KMC condition.Conclusion: Very preterm neonates appear to have endogenous mechanisms elicited through skin-to-skin maternal contact that decrease pain response, but not as powerfully as in older preterm neonates. The shorter recovery time in KMC is clinically important in helping maintain homeostasis.Trial Registration: (Current Controlled Trials) ISRCTN63551708. [ABSTRACT FROM AUTHOR]

Continuous professional development (CPD) is crucial for physicians to maintain and enhance their skills. In response to the changing context of CPD and health care, this study applied a design thinking approach to transform and modernise the Royal College of Physicians and Surgeons of Canada's Maintenance of Certification (MOC) Program. A member-wide survey and co-design sessions with physicians, CPD leaders, and patient representatives were conducted, emphasising the importance of their insights and experiences. The data revealed key themes for the programme such as fostering meaningful learning, addressing barriers to CPD, supporting collaboration, and responding to the need for modern, flexible CPD delivery methods. Using "empathy", "define", "ideate", "prototype", and "test" phases, we continuously refined the MOC framework of CPD activities based on comprehensive user experiences and needs insights. The revised framework was iteratively prototyped and validated to ensure it was user-friendly and aligned with professional and regulatory requirements. The findings underscore the effectiveness of the design thinking approach in creating a dynamic, responsive MOC framework that supports CPD and meets the evolving needs of medical professionals. This approach not only demonstrates the effectiveness of design thinking but also the importance of engaging users in the development process, making them feel valued and integral to the transformation of the MOC Program., Competing Interests: All the authors disclose they were full-time staff or contractors with the Royal College of Physicians and Surgeons of Canada when this process occurred. No external funding was used for this process., (© 2024 Royal college of physicians and surgeons of Canada. Published by Informa UK Limited, trading as Taylor & Francis Group.)

Prostate cancer (PCa) displays diverse intra-tumoral traits, impacting its progression and treatment outcomes. This study aimed to refine PCa cell culture conditions for dynamic monitoring of androgen receptor (AR) activity at the single-cell level. We introduced an extracellular matrix-Matrigel (ECM-M) culture model, enhancing cellular tracking during bioluminescence single-cell imaging while improving cell viability. ECM-M notably tripled the traceability of poorly adherent PCa cells, facilitating robust single-cell tracking, without impeding substrate permeability or AR response. This model effectively monitored AR modulation by antiandrogens across various PCa cell lines. Single-cell imaging unveiled heterogeneous antiandrogen responses within populations, correlating non-responsive cell proportions with drug IC50 values. Integrating ECM-M culture with the PSEBC-TSTA biosensor enabled precise characterization of ARi responsiveness within diverse cell populations. Our ECM-M model stands as a promising tool to assess heterogeneous single-cell treatment responses in cancer, offering insights to link drug responses to intracellular signaling dynamics. This approach enhances our comprehension of the nuanced and dynamic nature of PCa treatment responses.

A tumor microenvironment is characterized by its altered mechanical properties. However, most models remain unable to faithfully recreate the mechanical properties of a tumor. Engineered models based on the self-assembly method have the potential to better recapitulate the stroma architecture and composition. Here, we used the self-assembly method based on a bladder tissue model to engineer a tumor-like environment. The tissue-engineered tumor models were reconstituted from stroma-derived healthy primary fibroblasts (HFs) induced into cancer-associated fibroblast cells (iCAFs) along with an urothelium overlay. The iCAFs-derived extracellular matrix (ECM) composition was found to be stiffer, with increased ECM deposition and remodeling. The urothelial cells overlaid on the iCAFs-derived ECM were more contractile, as measured by quantitative polarization microscopy, and displayed increased YAP nuclear translocation. We further showed that the proliferation and expression of epithelial-to-mesenchymal transition (EMT) marker in the urothelial cells correlate with the increased stiffness of the iCAFs-derived ECM. Our data showed an increased expression of EMT markers within the urothelium on the iCAFs-derived ECM. Together, our results demonstrate that our tissue-engineered tumor model can achieve stiffness levels comparable to that of a bladder tumor, while triggering a tumor-like response from the urothelium.

Despite the biological interest in herring milt hydrolysate (HMH), its valorization is limited by its unpleasant odor resulting from the presence of mainly amine and carbonyl compounds. Recently, a deaerator was demonstrated as an interesting avenue to reduce the odorous content of HMH. However, the removal rate of amine and carbonyl compounds was highly dependent on the operating conditions, and the impact of such a process on the biological potential of HMH was not considered. Therefore, this study aimed to optimize the deaerator process by assessing the impacts of the combination of deaerator treatments at neutral and basic pH, the increase in pH from 10 to 11, and the substitution of NaOH by KOH on the odorous content and the antioxidant activity of HMH. Results showed that the highest deodorization rate of HMH was obtained when a deaerator treatment at neutral pH was combined with another one at basic pH using KOH for alkalization. This condition resulted in a decrease in the dimethylamine and trimethylamine contents by 70%, while certain compounds such as 2,3-pentanedione, methional, ( E , E )-2,4-heptadienal, or ( E , Z )-2,6-nonadienal were almost completely removed. Removal mechanisms of the targeted compounds were totally identified, and the performance of the developed process was confirmed by sensory analysis. Lastly, it was shown that the antioxidant potential of HMH was not affected by the deodorization process. These results demonstrated the feasibility of deodorizing a complex matrix without affecting its biological potential.

During the process of tumor growth, cancer cells will be subjected to intermittent hypoxia. This results from the delay in the development of the vascular network in relation to the proliferation of cancer cells. The hypoxic nature of a tumor has been demonstrated as a negative factor for patient survival. To evaluate the impact of hypoxia on the survival and migration properties of low and high-grade bladder cancer cell lines, two low-grade (MGHU-3 and SW-780) and two high-grade (SW-1710 and T24) bladder cancer cell lines were cultured in normoxic (20% O 2 ) or hypoxic atmospheric conditions (2% O 2 ). The response of bladder cancer cell lines to hypoxic atmospheric cell culture conditions was examined under several parameters, including epithelial-mesenchymal transition, doubling time and metabolic activities, thrombospondin-1 expression, whole Matrix Metallo-Proteinase activity, migration and resistance to oxidative stress. The low-grade cell line response to hypoxia was heterogeneous even if it tended to adopt a more aggressive profile. Hypoxia enhanced migration and pro-survival properties of MGHU-3 cells, whereas these features were reduced for the SW-780 cell line cultured under low oxygen tension. The responses of tested high-grade cell lines were more homogeneous and tended to adopt a less aggressive profile. Hypoxia drastically changed some of the bladder cancer cell line properties, for example matrix metalloproteinases expression for all cancer cells but also switch in glycolytic metabolism of low grade cancer cells. Overall, studying bladder cancer cells in hypoxic environments are relevant for the translation from in vitro findings to in vivo context., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Chabaud et al.)

Protein engineering approaches have been proposed to improve the inhibitory properties of plant cystatins against herbivorous arthropod digestive proteases, generally involving the site-directed mutagenesis of functionally relevant amino acids or the selection of improved inhibitor variants by phage display approaches. Here, we propose a novel approach where the function-related structural elements of a cystatin are substituted by the corresponding elements of an alternative cystatin. Inhibitory assays were first performed with 20 representative plant cystatins and model Cys proteases, including arthropod proteases, to appreciate the extent of functional variability among the plant cystatin family. The most, and less, potent of these cystatins were then used as 'donors' of structural elements to create hybrids of tomato cystatin SlCYS8 used as a model 'recipient' inhibitor. In brief, inhibitory activities against Cys proteases strongly differed from one plant cystatin to another, with K i (papain) values diverging by more than 30-fold and inhibitory rates against arthropod proteases varying by up to 50-fold depending on the enzymes assessed. In line with theoretical assumptions from docking models generated for different Cys protease-cystatin combinations, structural element substitutions had a strong impact on the activity of recipient cystatin SlCYS8, positive or negative depending on the basic inhibitory potency of the donor cystatin. Our data confirm the wide variety of cystatin inhibitory profiles among plant taxa. They also demonstrate the usefulness of these proteins as a pool of discrete structural elements for the design of cystatin variants with improved potency against herbivorous pest digestive Cys proteases., (© 2021 Federation of European Biochemical Societies.)