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Amphibians have a great diversity of bioactive peptides in their skin. The cDNA prepro-peptide sequencing allowed the identification of five novel mature peptides expressed in the skin of Boana pulchella, four with similar sequences to hylin peptides having a cationic amphipathic-helical structure. Whole mature peptides and some of their fragments were chemically-synthesized and tested against Gram-positive and Gram-negative bacterial strains. The mature peptide hylin-Pul3 was the most active, with a MIC= 14 µM against Staphylococcus aureus. Circular dichroism assays indicated that peptides are mostly unstructured in buffer solutions. Still, adding large unilamellar vesicles composed of dimyristoyl phosphatidylcholine and dimyristoylphosphatidylglycerol increased the α-helix content of novel hylins. These results demonstrate the strong influence of the environment on peptide conformation and highlight its significance while addressing the pharmacology of peptides and their biological function in frogs., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Internationally, the health-care sector has been slower than many other sectors in reducing its carbon emissions and broader environmental footprint. Incrementally, tertiary education institutions are changing their focus to integrate environmental and social objectives, including planetary health, into teaching, research, and how the campus is operated. Planetary health and sustainable health-care are emerging topics in the education of health professionals. However, they have largely been limited to specific knowledge rooted in western epistemology with ad hoc curricula that do not consider the complex interdependence of ecosystems and human health. Because of the need to prepare the current and future health-care workforce for planetary consciousness and related practices, in this Personal View we provide an innovative case study that uses Indigenist health humanities (eg, narrative portraiture) and arts-based education strategies to offer a different way of seeing, knowing, and understanding planetary health. Embedding Indigenous knowledges and voices into planetary health education is an important first step in decolonising learning in health professional education., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Uncertainty tolerance, individuals' perceptions/responses to uncertain stimuli, is increasingly recognized as critical to effective healthcare practice. While the Covid-19 pandemic generated collective uncertainty, healthcare-related uncertainty is omnipresent. Correspondingly, there is increasing focus on uncertainty tolerance as a health professional graduate "competency," and a concomitant interest in identifying pedagogy fostering learners' uncertainty tolerance. Despite these calls, practical guidelines for educators are lacking. There is some initial evidence that anatomy education can foster medical students' uncertainty tolerance (e.g., anatomical variation and dissection novelty), however, there remains a knowledge gap regarding robust curriculum-wide uncertainty tolerance teaching strategies. Drawing upon humanities, arts and social sciences (HASS) educators' established uncertainty tolerance pedagogies, this study sought to learn from HASS academics' experiences with, and teaching practices related to, uncertainty pedagogy using a qualitative, exploratory study design. Framework analysis was undertaken using an abductive approach, wherein researchers oscillate between inductive and deductive coding (comparing to the uncertainty tolerance conceptual model). During this analysis, the authors analyzed ~386 min of data from purposively sampled HASS academics' (n = 14) discussions to address the following research questions: (1) What teaching practices do HASS academics' perceive as impacting learners' uncertainty tolerance, and (2) How do HASS academics execute these teaching practices? The results extend current understanding of the moderating effects of education on uncertainty tolerance and supports prior findings that the anatomy learning environment is ripe for supporting learner uncertainty tolerance development. This study adds to growing literature on the powerful moderating effect education has on uncertainty tolerance and proposes translation of HASS uncertainty tolerance teaching practices to enhance anatomy education., (© 2022 The Authors. Anatomical Sciences Education published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Fibrous hydrogels are a key component of soft animal tissues. They support cellular functions and facilitate efficient mechanical communication between cells. Due to their nonlinear mechanical properties, fibrous materials display non-trivial force propagation at the microscale, that is enhanced compared to that of linear-elastic materials. In the body, tissues are constantly subjected to external loads that tense or compress them, modifying their micro-mechanical properties into an anisotropic state. However, it is unknown how force propagation is modified by this isotropic-to-anisotropic transition. Here, force propagation in tensed fibrin hydrogels is directly measured. Local perturbations are induced by oscillating microspheres using optical tweezers. 1-point and 2-point microrheology are combined to simultaneously measure the shear modulus and force propagation. A mathematical framework to quantify anisotropic force propagation trends is suggested. Results show that force propagation becomes anisotropic in tensed gels, with, surprisingly, stronger response to perturbations perpendicular to the axis of tension. Importantly, external tension can also increase the range of force transmission. Possible implications and future directions for research are discussed. These results suggest a mechanism for favored directions of mechanical communication between cells in a tissue under external loads., (© 2022 The Authors. Small published by Wiley-VCH GmbH.)

The large HDL particles generated by administration of cholesteryl ester transfer protein inhibitors (CETPi) remain poorly characterized, despite their potential importance in the routing of cholesterol to the liver for excretion, which is the last step of the reverse cholesterol transport. Thus, the effects of the CETPi dalcetrapib and anacetrapib on HDL particle composition were studied in rabbits and humans. The association of rabbit HDL to the LDL receptor (LDLr) in vitro was also evaluated. New Zealand White rabbits receiving atorvastatin were treated with dalcetrapib or anacetrapib. A subset of patients from the dal-PLAQUE-2 study treated with dalcetrapib or placebo were also studied. In rabbits, dalcetrapib and anacetrapib increased HDL-C by more than 58% (P < 0.01) and in turn raised large apo E-containing HDL by 66% (P < 0.001) and 59% (P < 0.01), respectively. Additionally, HDL from CETPi-treated rabbits competed with human LDL for binding to the LDLr on HepG2 cells more than control HDL (P < 0.01). In humans, dalcetrapib increased concentrations of large HDL particles (+69%, P < 0.001) and apo B-depleted plasma apo E (+24%, P < 0.001), leading to the formation of apo E-containing HDL (+47%, P < 0.001) devoid of apo A-I. Overall, in rabbits and humans, CETPi increased large apo E-containing HDL particle concentration, which can interact with hepatic LDLr. The catabolism of these particles may depend on an adequate level of LDLr to contribute to reverse cholesterol transport., Competing Interests: Conflict of interest E. J. N. and C. M. were previously employees of F. Hoffmann-La Roche Ltd. J.-C. T. has received research grants from Amarin, AstraZeneca, Ceapro, DalCor Pharmaceuticals, Esperion, F. Hoffmann-La Roche Ltd., Ionis, Novartis, Pfizer, and RegenXBio; honoraria from AstraZeneca, DalCor Pharmaceuticals, HLS Pharmaceuticals, Pendopharm, and Pfizer; holds minor equity interest in DalCor Pharmaceuticals; and is mentioned as an author of a patent on pharmacogenomics-guided dalcetrapib treatment. The other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest None to declare.

In this study, we report the isolation, characterization, and synthesis of the peptide BmT-2 belonging to the tryptophyllins family, isolated from the venom of the snake Bothrops moojeni . This is the first time a tryptophyllin is identified in snake venom. We tested whether BmT-2 had cytotoxic effects and antioxidant activity in a set of experiments that included both in vitro and cell-based assays. BmT-2 presented a radical scavenging activity toward ABTS • and AAPH-derived radicals. BmT-2 protected fluorescein, DNA molecules, and human red blood cells (RBCs) from free radicals generated by the thermal decomposition of AAPH. The novel tryptophyllin was not toxic in cell viability tests, where it (up to 0.4 mg/mL) did not cause hemolysis of human RBCs and did not cause significant loss of cell viability, showing a CC 50 > 1.5 mM for cytotoxic effects against SK-N-BE(2) neuroblastoma cells. BmT-2 prevented the arsenite-induced upregulation of Nrf2 in Neuro-2a neuroblasts and the phorbol myristate acetate-induced overgeneration of reactive oxygen species and reactive nitrogen species in SK-N-BE(2) neuroblastoma cells. Electronic structure calculations and full atomistic reactive molecular dynamics simulations revealed the relevant contribution of aromatic residues in BmT-2 to its antioxidant properties. Our study presents a novel peptide classified into the family of the tryptophyllins, which has been reported exclusively in amphibians. Despite the promising results on its antioxidant activity and low cytotoxicity, the mechanisms of action of BmT-2 still need to be further elucidated.

Odor hedonic perception (pleasant/unpleasant character) is considered as the first and one of the most prominent dimensions in olfaction and is known to depend on several parameters. Among them, the relation between the odorant concentration and the hedonic estimation has been widely studied. However, few studies have considered odor hedonic ratings (OHR) in relation to individual detection thresholds (IDT). Thus, the aim of this study was to determine olfactory detection thresholds and to describe hedonic rating variations from individual thresholds to higher concentrations. IDT were performed for two pleasant (apple and jasmine) and two unpleasant (durian and trimethylamine) odorant stimuli. The experimenter presented one by one in a randomized order, the different odorant concentrations above IDT. Participants rated odor hedonic valence of these stimuli on a visual analog scale. Results showed, except for trimethylamine, the same relationship between hedonic ratings and stimulus concentration, i.e., an increase of pleasantness (apple and jasmine)/unpleasantness (durian) ratings at low and middle concentrations followed by a plateau at high concentrations. Correlations between OHR and concentrations as well as between OHR and threshold steps were always significant. Moreover, comparisons between both conditions showed that the correlation coefficient was significantly higher for trimethylamine (and a trend for apple) when IDTs were considered, while no difference was found for jasmine and durian. Overall, results suggested that the relationship between OHR and IDT is odor specific. These findings contribute to explain the large variability of the hedonic tone (i.e., weakly vs. very pleasant, weakly vs. very unpleasant) at specific concentration in the general population and could serve future research in this field (e.g., olfactory preferences in nutrition studies, anhedonia in psychiatric disorders…)., (© 2022. The Author(s).)

Multiple membrane-shaping and remodeling processes are associated with tetraspanin proteins by yet unknown mechanisms. Tetraspanins constitute a family of proteins with four transmembrane domains present in every cell type. Prominent examples are tetraspanin4 and CD9, which are required for the fundamental cellular processes of migrasome formation and fertilization, respectively. These proteins are enriched in curved membrane structures, such as cellular retraction fibers and oocyte microvilli. The factors driving this enrichment are, however, unknown. Here, we revealed that tetraspanin4 and CD9 are curvature sensors with a preference for positive membrane curvature. To this end, we used a biomimetic system emulating membranes of cell retraction fibers and oocyte microvilli by membrane tubes pulled out of giant plasma membrane vesicles with controllable membrane tension and curvature. We developed a simple thermodynamic model for the partitioning of curvature sensors between flat and tubular membranes, which allowed us to estimate the individual intrinsic curvatures of the two proteins. Overall, our findings illuminate the process of migrasome formation and oocyte microvilli shaping and provide insight into the role of tetraspanin proteins in membrane remodeling processes.

Objective: Climate change poses a significant threat to humanity and human activity is largely responsible for it. Clinical microbiology laboratories have their unintended shares in carbon dioxide (CO 2 ) emissions. The aim of this study is to estimate CO 2 emission of a clinical microbiology laboratory and to propose initiatives to reduce the emissions., Methods: CO 2 emission of instruments was estimated based on their electricity consumption. CO 2 emitted in producing consumables was estimated by weighing the consumables needed to perform major tests in a large academic hospital. A systematic literature review was performed to identify studies on the impact of clinical microbiology laboratories on the environment. A short survey was sent to four major manufacturers of agar plates on initiatives to reduce the environmental impact of their products. Opinion was given on activities that can reduce CO 2 emission in laboratories., Results: The study shows that the largest amount of CO 2 emission in the microbiological laboratories comes from consumables and personnel commuting. For example, the production and transportation of agar plates needed to culture samples for a year in a hospital with 1320 beds result in 16 590 kg CO 2 is emitted. All survey participants mentioned that they were committed to reduce environmental impact of their products. The initiatives to reduce CO 2 emission can be performed at the laboratory and at policy level, such as reducing the number of tests to only the necessary amount to reduce consumables., Discussion: The calculations contribute to map CO 2 -related emissions in clinical microbiology laboratory activities, and the proposed initiatives to reduce the CO 2 may serve as starting point for further discussions., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This study aimed to evaluate whether the implementation of extra perioperative safety measures and precautions through adopted standard operating procedures (SOPs) to ensure optimal anti-microbial conditions has led to less surgical site infections (SSI) after alloplastic breast reconstruction (BR)., Methods: This retrospective study compared two Cohorts of patients treated before and after the implementation of new SOPs (2009-2014: Cohort 1 versus 2014-2019: Cohort 2). Multivariate logistic regression analyses, adjusting for patient confounders, were implemented to compare SSI incidence between both Cohorts., Results: Overall, SSI incidence was equal in both groups (10%, p = 0.545). The incidence of deep SSI was 9% for Cohort 1 and 5% for Cohort 2 (p = 0.074). Incidence of SSI-related explantation was 8% and 5%, respectively (p = 0.136). After adjusting for patient confounders, no statistically significant difference was seen between both Cohorts in overall SSI, deep SSI incidence, and explantation due to SSI (OR adjusted : -0.31, p = 0.452, OR adjusted: 0.16, p = 0.747 and OR adjusted: 0.18, p = 0.712). Higher BMI, smoking, one-stage BR, and immediate BR were associated with the risk for SSI (p<0.001, p = 0.036, p<0.001, and p = 0.022, respectively)., Conclusion: Extra safety measures to assure optimal anti-microbial conditions did not contribute to lower SSI incidence or SSI-related explantation after alloplastic BR. Confounders such as BMI, smoking, immediate BR, and one-stage BR were correlated to an increased risk for overall SSI, deep SSI, and SSI-related explantation of TE/implants., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Informed decision-making is a vital component of midwifery philosophy and a core recommendation of the global respectful maternity care charter; however, women and midwives report a lack of informed decision-making in actual practice. Research reveals informed decision-making improves physical and mental health outcomes for women, regardless of childbearing experience, and is a protective factor for midwives' job satisfaction. There is currently little known about midwives' experiences of facilitating informed decision-making, and associated barriers., Objective: To critically appraise and synthesize the best qualitative evidence exploring midwives' experiences of facilitating women's informed decision-making., Methods: A systematic search of key databases and grey literature for qualitative research in English language published between 2010-2019. Quality assessment followed CASP guidelines and this review is reported in accordance with PRISMA guidelines. Thirteen studies were included in the final review. Data were synthesised narratively., Results: Midwives were shown to have a strong desire to facilitate informed decision-making, yet reported a disparity between philosophy and practice due to multiple barriers. Barriers included; lack of specific knowledge and training, fear of blame and litigation, structural constraints including lack of time and fragmented models of midwifery care, and multidisciplinary philosophical disparities., Conclusion: Existing literature identifies informed decision-making is the gold-standard in providing safe and respectful maternity care, yet this review demonstrates that it is not well executed in actual practice. Midwives recognise this disparity and identify barriers which require urgent education, research, policy and practice solutions., Competing Interests: Declaration of Competing Interest As one author (HH) had published a study which was included in the final 13 studies, she was not included in the review, quality appraisal, or data extraction process for this particular study., (Copyright © 2022. Published by Elsevier Ltd.)

Introduction: Inflammatory bowel disease (IBD) is characterized by a disturbed gut microbiota composition. Patients with IBD have both elevated mucosal and serum levels of IgG-antibodies directed against bacterial antigens, including flagellins. In this study, we aimed to determine to which intestinal bacteria the humoral immune response is directed to in patients with IBD., Methods: Fecal and serum samples were collected from patients with IBD ( n =55) and age- and sex-matched healthy controls ( n =55). Fecal samples were incubated with autologous serum and IgG-coated fractions were isolated by magnetic-activated cell sorting (MACS) and its efficiency was assessed by flow cytometry. The bacterial composition of both untreated and IgG-coated fecal samples was determined by 16S rRNA-gene Illumina sequencing., Results: IgG-coated fecal samples were characterized by significantly lower microbial diversity compared to the fecal microbiome. Both in patients with IBD and controls, serum IgG responses were primarily directed to Streptococcus , Lactobacillus , Lactococcus , Enterococcus , Veillonella and Enterobacteriaceae , as well as against specific Lachnospiraceae bacteria, including Coprococcus and Dorea (all P <0.001), and to Ruminococcus gnavus -like bacteria ( P <0.05). In contrast, serological IgG responses against typical commensal, anaerobic and colonic microbial species were rather low, e.g. to the Lachnospiraceae members Roseburia and Blautia , to Faecalibacterium , as well as to Bacteroides . Patients with IBD showed more IgG-coating of Streptococcus , Lactobacillus , and Lactococcus bacteria compared to healthy controls (all P <0.05). No differences in IgG-coated bacterial fractions were observed between Crohn's disease and ulcerative colitis, between active or non-active disease, nor between different disease locations., Conclusion: The IgG immune response is specifically targeted at distinct intestinal bacterial genera that are typically associated with the small intestinal microbiota, whereas responses against more colonic-type commensals are lower, which was particularly the case for patients with IBD. These findings may be indicative of a strong immunological exposure to potentially pathogenic intestinal bacteria in concordance with relative immune tolerance against commensal bacteria., Competing Interests: GD and HH received an unrestricted research grant from Royal DSM. GD received speaker fees from Pfizer, Abbvie and Janssen Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bourgonje, Roo-Brand, Lisotto, Sadaghian Sadabad, Reitsema, de Goffau, Faber, Dijkstra and Harmsen.)

Tryptophyllins constitute a heterogeneous group of peptides that are one of the first classes of peptides identified from amphibian's skin secretions. Here, we report the structural characterization and antioxidant properties of a novel tryptophyllin-like peptide, named PpT-2, isolated from the Iberian green frog Pelophylax perezi. The skin secretion of P. perezi was obtained by electrical stimulation and fractionated using RP-HPLC. De novo peptide sequencing was conducted using MALDI MS/MS. The primary structure of PpT-2 (FPWLLS-NH 2 ) was confirmed by Edman degradation and subsequently investigated using in silico tools. PpT-2 shared physicochemical properties with other well-known antioxidants. To test PpT-2 for antioxidant activity in vitro, the peptide was synthesized by solid phase and assessed in the chemical-based ABTS and DPPH scavenging assays. Then, a flow cytometry experiment was conducted to assess PpT-2 antioxidant activity in oxidatively challenged murine microglial cells. As predicted by the in silico analyses, PpT-2 scavenged free radicals in vitro and suppressed the generation of reactive species in PMA-stimulated BV-2 microglia cells. We further explored possible bioactivities of PpT-2 against prostate cancer cells and bacteria, against which the peptide exerted a moderate antiproliferative effect and negligible antimicrobial activity. The biocompatibility of PpT-2 was evaluated in cytotoxicity assays and in vivo toxicity with Galleria mellonella. No toxicity was detected in cells treated with up to 512 µg/ml and in G. mellonella treated with up to 40 mg/kg PpT-2. This novel peptide, PpT-2, stands as a promising peptide with potential therapeutic and biotechnological applications, mainly for the treatment/prevention of neurodegenerative disorders., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: To build complex digital skills and capability required by digitally-driven work environments, we must first understand nursing students' baseline digital literacy if educators are to develop a fit for purpose curriculum underpinned by digital health technologies., Objective: To determine first-year pre-registration nursing students' perceived baseline digital literacy before their first clinical placement., Design: Prospective cohort study., Settings: Two universities in Australia in 2020., Participants: Students enrolled in pre-registration nursing programs at Bachelor's and Master's level., Methods: Participants (N = 205) completed an online 27-item survey composed of a Likert-type scale, forced-choice items, and open-ended questions. Data were analyzed with descriptive statistics., Results: Participants engaged with digital technology early in life, with 49.75% students using some form of digital technology before ten years of age. Students reported the highest daily use of technology to search the internet for information (92%), online social networking (68.3%) and watching videos (67%). Most students expressed the least confidence in identifying different types of portable storage devices (24.1% Master's students; 41.7% Bachelor's students), describing the advantages of a digital camera (39.3% Master's students; 48.3% Bachelor's students), and totaling numbers in spreadsheets (22.8% Masters students; 48.3% Bachelor's students). No statistical differences were observed between the two universities or the two cohorts in terms of perceived confidence in using technology and software applications to support their learning. Interestingly, 24.7% of participants expressed high confidence in using electronic medical records without prior training, which may reflect positive attitude towards engaging with unknown digital technologies., Conclusions: Nursing students are frequent internet and social media users. However, despite positive attitudes to digital technology and widespread presence of digital technology in students' lives, deficits in students' confidence in using digital technology and software required for learning persist. Targeted digital literacy education interventions are needed as part of foundational nursing studies to improve nursing students' baseline digital literacy before commencing clinical placement. These should be scaffolded across the program to ensure an effective transition to nursing practice in evolving digitally-driven healthcare environments., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: There is conflicting and limited information regarding factors that influence undergraduate nursing students' academic and clinical performance prior to entry to practice., Objective: To identify factors influencing the academic and clinical performance of undergraduate nursing students throughout the course., Design: Mixed methods study utilizing a retrospective cohort and a qualitative study., Setting: Monash University, Melbourne, Australia., Participants: Longitudinal existing data of nursing undergraduate students who commenced in 2017 ( n = 176) and 2018 ( n = 76), and two focus groups with final year nursing students were analyzed., Methods: Retrospective students' records were used to determine the students' academic and clinical performance using the weighted average mark (WAM) of the theoretical and clinical components of the curriculum, separately. The WAM considered the year level of each unit and was scored out of 100. Multivariate linear regression was used to determine predictor factors of academic and clinical performance. Variables include entry cohort (with no previous nursing qualification vs. diploma of nursing), admission category (domestic vs. international), campus (metropolitan vs. outer metropolitan), and secondary school (year 12) results. Two focus group discussions were conducted and thematically analyzed., Results: More than two-thirds of the students were aged 18-20 years and mainly female. Almost 20% of the participants were international students. Students with higher secondary school (year 12) results and studying at the outer metropolitan campus achieved a higher academic performance while international students had significantly lower academic performance compared to domestic students. Students with a previous diploma of enrolled nursing and international students had lower clinical performance. Students identified that a comprehensive orientation, interactive curriculum, formal and informal support structure, and educator qualities influenced their academic and/or clinical performance., Conclusions: A supportive educational environment with an interactive curriculum may enhance students' academic and clinical performance and readiness for practice. Furthermore, targeted interventions for international students, those with lower secondary school (year 12) results, and those with a former diploma of nursing may be required to increase academic and clinical performance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fooladi, Karim, Vance, Walker, Zanjani, Ilic and Brand.)

Objective: To explore the experiences of newly qualified registered graduate nurses' clinical and professional learning experiences, during their first six-months of post registration employment within a graduate nurse transition program in a Neonatal Intensive Care Unit (NICU)., Method: Narrative inquiry with thematic analysis was used to explore the newly qualified registered graduate nurses' accounts via semi-structured interviews, conducted between January 2018 - January 2019, of their clinical and professional learning during their employment in the Neonatal Intensive Care Unit., Setting: In total, eight newly qualified registered graduate nurses employed at two Western Australian Hospitals sites were recruited., Findings: Themes identified included: feeling unprepared; experiences of horizontal violence; the need for a supportive structural environment and seeking feedback. Participants reported overwhelming feelings of stress, emotional exhaustion, concerns for patient safety and for some, fear of early career burnout., Conclusion: In this study, newly qualified registered graduate nurses were clinically underprepared for entering a Neonatal Intensive Care Unit with all participants reporting high levels of psychosocial distress. This was further compounded by a lack of structured support, horizontal violence, and inadequate or no regular feedback from preceptors, resulting from a negative workplace culture and poor educator behaviours. Recommendations for improving the experiences of newly qualified registered graduate nurses employed in the Neonatal Intensive Care are discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

(1) Background: Eye drops are the most common route of administration for ophthalmic medications. Administering drops can be a major hurdle for patients, potentially resulting in noncompliance and treatment failure. The purpose of this study is to compare the efficacy and safety of two different aids and the conventional bottle for eye drop instillation; (2) Methods: An interventional crossover study involving standard eye drop bottle, Opticare aid and Autodrop aid. The study included healthy subjects without a history of regular eye drop use; (3) Results: Twenty-six subjects were enrolled. Of those subjects, 96% and 92% were able to assemble the eye drop bottle into the Autodrop and the Opticare aids, respectively. Subjective assessment indicated that Autodrop was significantly easier to assemble than Opticare (95% CI: -1.6802 to -0.1659, p = 0.02). When using either aid, there was no contamination of the bottle tip, which occurred in 46% of subjects when no aid was used ( p = 0.0005). Fewer drops were expelled when using the conventional bottle as compared to the aids ( p = 0.05 compared to Autodrop, p = 0.1 compared to Opticare); (4) Conclusions: Autodrop and Opticare can assist patients with eye drop placement. These aids completely prevented bottle tip contamination, which was frequently observed when the conventional bottle was used alone.

Background: In the ever-changing and complex healthcare environment, nurses encounter challenging situations that may involve a clash between their personal and professional values resulting in a profound impact on their practice. Nevertheless, there is a dearth of literature on how nurses develop their personal-professional values., Aim: The aim of this study was to understand how nurses develop their foundational values as the base for their value system., Research Design: A constructivist grounded theory methodology was employed to collect multiple data sets, including face-to-face focus group and individual interviews, along with anecdote and reflective stories., Participants and Research Context: Fifty-four nurses working across various nursing settings in Indonesia were recruited to participate., Ethical Considerations: Ethics approval was obtained from the Monash University Human Ethics Committee, project approval number 1553., Findings: Foundational values acquisition was achieved through family upbringing, professional nurse education and organisational/institutional values reinforcement. These values are framed through three reference points: religious lens, humanity perspective and professionalism. This framing results in a unique combination of personal-professional values that comprise nurses' values system. Values are transferred to other nurses either in a formal or informal way as part of one's professional responsibility and customary social interaction via telling and sharing in person or through social media., Discussion: Values and ethics are inherently interweaved during nursing practice. Ethical and moral values are part of professional training, but other values are often buried in a hidden curriculum, and attained and activated through interactions during nurses' training., Conclusion: Developing a value system is a complex undertaking that involves basic social processes of attaining, enacting and socialising values. These processes encompass several intertwined entities such as the sources of values, the pool of foundational values, value perspectives and framings, initial value structures, and methods of value transference.

Odor hedonic evaluation (pleasant/unpleasant) is considered as the first and one of the most prominent dimension in odor perception. While sex differences in human olfaction have been extensively explored, gender effect in hedonic perception appears to be less considered. However, a number of studies have included comparisons between men and women, using different types of measurements (psychophysical, psychophysiological,…). This overview presents experimental works with non-specific and body odors separately presented as well as experimental studies comparing healthy participants vs patients with psychiatric disorders. Contrary to sensitivity, identification or discrimination, the overall literature tends to prove that no so clear differences occur in odor hedonic judgment between men and women. On the whole, gender effect appears more marked for body than non-specific odors and is almost never reported in psychiatric diseases. These findings are discussed in relation to the processes classically implied in pleasantness rating and emotional processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bontempi, Jacquot and Brand.)

Background and Aims: The anti-inflammatory agent colchicine is gaining interest as a treatment for coronary artery disease. However, the effects of colchicine in atherosclerotic animal models are mostly unknown. This study aimed to evaluate colchicine in a rabbit model of atherosclerosis., Methods: Twenty-two rabbits were fed a 0.5% cholesterol-enriched diet for 10 weeks and then randomized to receive either oral saline (n=11) or colchicine (350 μg/kg/day; n=11) for 6 weeks, with 0.2% cholesterol-diet during the treatment period. We performed intravascular ultrasound imaging (at start and end of treatment) and histology analyses of the descending thoracic aorta. Leucocyte activation was assessed in vitro on blood samples obtained during treatment., Results: Colchicine prevented positive aortic vascular remodelling ( p =0.029 vs placebo). This effect was even more marked at high plasma cholesterol level (third quartile of plasma cholesterol, p =0.020). At high cholesterol level, both atherosclerotic plaque and media areas on histomorphology were reduced by colchicine compared to placebo ( p =0.031 and p =0.039, respectively). Plaque fibrosis and macrophage area were reduced by colchicine (Masson's trichrome stain: p =0.038; RAM-11: p =0.026). The plaque vulnerability index, assessed by histology, was reduced by colchicine ( p =0.040). Elastin/type I collagen ratio in media was significantly higher with colchicine compared to placebo ( p =0.013). At a high level of plasma cholesterol, in vitro LPS challenge revealed a decrease in monocyte activation following treatment with colchicine ( p <0.001) and no change in the placebo group ( p =0.353)., Conclusions: Colchicine decreases plaque vulnerability with reductions in plaque inflammation, medial fibrosis, outward vascular remodelling and ex vivo monocyte activation., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Tardif reports receiving grant support from Amarin, Esperion, Ionis PharmaceuticalsIonis Pharmaceuticals and RegenXBio, receiving grant support and honoraria from AstraZeneca, Pfizer and Sanofi, receiving grant support and honoraria from and having minor equity interest in DalCor PharmaceuticalsDalCor Pharmaceuticals, holding a pending patent (US20170233812A1) on genetic markers for predicting responsiveness to therapy with a high-density lipoprotein (HDL)–raising or HDL mimicking agent, and holding pending patents (62/935,751 and 62/935,865) on methods for using low-dose colchicine after myocardial infarction, licensed to Montreal Heart Institute (Dr. Tardif has waived his rights in colchicine patents and does not stand to gain financially)., (© 2021 The Authors.)

Snake venoms are important sources of bioactive molecules, including those with antiparasitic activity. Cathelicidins form a class of such molecules, which are produced by a variety of organisms. Batroxicidin (BatxC) is a cathelicidin found in the venom of the common lancehead ( Bothrops atrox ). In the present work, BatxC and two synthetic analogues, BatxC(C-2.15Phe) and BatxC(C-2.14Phe)des-Phe1, were assessed for their microbicidal activity. All three peptides showed a broad-spectrum activity on Gram-positive and -negative bacteria, as well as promastigote and amastigote forms of Leishmania ( Leishmania ) amazonensis . Circular dichroism (CD) and nuclear magnetic resonance (NMR) data indicated that the three peptides changed their structure upon interaction with membranes. Biomimetic membrane model studies demonstrated that the peptides exert a permeabilization effect in prokaryotic membranes, leading to cell morphology distortion, which was confirmed by atomic force microscopy (AFM). The molecules considered in this work exhibited bactericidal and leishmanicidal activity at low concentrations, with the AFM data suggesting membrane pore formation as their mechanism of action. These peptides stand as valuable prototype drugs to be further investigated and eventually used to treat bacterial and protozoal infections.

What Is Known on the Subject: Integrating strengths-based, co-produced, consumer-driven resources into mental health workforce education has the potential to dissolve hierarchical mental health care relationships., What the Paper Adds to Existing Knowledge: Humanities-based pedagogy that draws from photography and multi-voiced narratives is a powerful reflective learning tool to bridge clinical and human experiences of Borderline Personality Disorder (BPD). The Depth of Field reflective learning methodology aims to provoke, prod, reveal and challenge assumptions and/or unconscious bias towards BPD and stimulate raw and reflective discussions that have the potential to inspire critical reflection and move health professionals towards more humanistic, recovery centred models of mental health care., What Are the Implications for Mental Health Nursing: At the core of co-production in research, education and practice lies a reciprocal, transformational learning experience. This relationship needs to be further explored in order to reframe mental health education that honours and legitimizes consumers as experts of their own lives and recovery experiences., (© 2020 John Wiley & Sons Ltd.)

Context: Community and consumer involvement in health professions education (HPE) is of growing interest among researchers and educators, particularly in preparing health care graduates to effectively learn from, and collaborate with, people with lived experience of health issues. However, to date there has been limited direction on methodological approaches to engage health care consumers in the research and co-design of HPE., Approach: In this paper, we describe the background to our work with health care consumers including the five core principles for successful co-design (inclusive; respectful; participative; iterative; outcomes focused) and how they can be applied as a research approach in HPE. We introduce the use of arts and humanities-based teaching methodologies including engagement, meaning-making and translational education strategies to illustrate how this research approach has been applied to reframe mental health education and practice in Australia. Furthermore, we share some reflective insights on the opportunities and challenges inherent in using a co-design research approach in HPE., Conclusions: For the consumer voice to be embedded across HPE, there needs to be a collective commitment to curriculum redesign. This paper advances our understandings of the educational research potential of working with health care consumers to co-design rich and authentic learning experiences in HPE. Co-design research approaches that partner with and legitimise health care consumers as experts by experience may better align education and health professional practice with consumers' actual needs, an important first step in transforming hierarchical health care relationships towards more humanistic models of care., (© 2020 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

Background: Steering planetary and human health towards a more sustainable future demands educated and prepared health professionals., Aim: This research aimed: to explore health professions educators' sustainable healthcare education (SHE) knowledge, attitudes, self-efficacy and teaching practices across 13 health professions courses in one Australian university., Methods: Utilising a sequential mixed-methods design: Phase one (understanding) involved an online survey to ascertain educators' SHE knowledge, attitudes, self-efficacy and teaching practices to inform phase two (solution generation), 'Teach Green' Hackathon. Survey data was descriptively analysed and a gap analysis performed to promote generation of solutions during phase two. Results from the hackathon were thematically analysed to produce five recommendations., Results: Regarding SHE, survey data across 13 health professions disciplines ( n  = 163) identified strong content knowledge (90.8%); however, only (36.9%) reported confidence to 'explain' and (44.2%) to 'inspire' students. Two thirds of participants (67.5%) reported not knowing how best to teach SHE. Hackathon data revealed three main influencing factors: regulatory, policy and socio-cultural drivers., Conclusions: The five actionable recommendations to strengthen interdisciplinary capacity to integrate SHE include: inspire multi-level leadership and collaboration; privilege student voice; develop a SHE curriculum and resources repository; and integrate SHE into course accreditation standards.

Intragenic antimicrobial peptides (IAPs) are internal sequences of proteins with physicochemical similarities to Antimicrobial Peptides (AMPs) that, once identified and synthesized as individual entities, present antimicrobial activity. Many mature proteins encoded by the genomes of virtually any organism may be regarded as inner reservoirs of IAPs, conferring them ample biotechnological potential. However, IAPs may also share shortcomings with AMPs, such as low half-life in biological media and non-specific adsorption in eukaryotic cells. The present manuscript reports a translational approach that encompasses the uncovering of two novel IAPs from human proteins as well as the first results concerning the incorporation and sustained release of one of these peptides from ureasil-polyether hybrid polymeric films. For such, the software Kamal was used to scan putative IAPs in the human proteome, and two peptides, named Hs05 and Hs06, were identified, synthesized, and tested as antimicrobials. Biophysical assays were conducted using model phospholipid vesicles and 1 H NMR solution structures in phospholipid micelles were obtained for the IAP Hs05. This peptide was incorporated in a polymeric matrix composed of the ureasil/PPO-PEO-PPO triblock copolymer, and the resulting films were evaluated by atomic force microscopy and imaging mass spectrometry. The release rate of Hs05 from the polymeric matrix was assessed and the antimicrobial activity of Hs05-loaded hybrid polymeric films was evaluated against the bacterium Escherichia coli. This study represents the first steps towards the development of polymeric films enriched with IAPs obtained from the human proteome as sustained release devices for topical application., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The acute respiratory distress syndrome (ARDS) is characterized by intense dysregulated inflammation leading to acute lung injury (ALI) and respiratory failure. There are no effective pharmacologic therapies for ARDS. Colchicine is a low-cost, widely available drug, effective in the treatment of inflammatory conditions. We studied the effects of colchicine pre-treatment on oleic acid-induced ARDS in rats. Rats were treated with colchicine (1 mg/kg) or placebo for three days prior to intravenous oleic acid-induced ALI (150 mg/kg). Four hours later they were studied and compared to a sham group. Colchicine reduced the area of histological lung injury by 61%, reduced lung edema, and markedly improved oxygenation by increasing PaO2/FiO2 from 66 ± 13 mmHg (mean ± SEM) to 246 ± 45 mmHg compared to 380 ± 18 mmHg in sham animals. Colchicine also reduced PaCO2 and respiratory acidosis. Lung neutrophil recruitment, assessed by myeloperoxidase immunostaining, was greatly increased after injury from 1.16 ± 0.19% to 8.86 ± 0.66% and significantly reduced by colchicine to 5.95 ± 1.13%. Increased lung NETosis was also reduced by therapy. Circulating leukocytosis after ALI was not reduced by colchicine therapy, but neutrophils reactivity and CD4 and CD8 cell surface expression on lymphocyte populations were restored. Colchicine reduces ALI and respiratory failure in experimental ARDS in relation with reduced lung neutrophil recruitment and reduced circulating leukocyte activation. This study supports the clinical development of colchicine for the prevention of ARDS in conditions causing ALI., Competing Interests: I have read the journal's policy and the authors of this manuscript have no competing interests to declare.

Correction for 'Live cell single molecule tracking and localization microscopy of bioorthogonally labeled plasma membrane proteins' by Andres I. König et al., Nanoscale, 2020, 12, 3236-3248, DOI: 10.1039/C9NR08594G.

This article was migrated. The article was marked as recommended. Using three human body systems as a metaphor, this paper will discuss how the art of teaching, including the conditions in which students thrive can remedy longstanding curriculum diseases. Based on the concept of a living curriculum, the importance of curiosity, exposing vulnerability, social and collaborative learning, communication and reflective learning processes in transforming teaching and inspiring learning will be explored., (Copyright: © 2020 Brand G.)

Integrating co-produced humanities-based pedagogy into patient and workforce education is of growing interest. The aim of our Depth of Field: Exploring Stroke Recovery project grew from a strong commitment to use patients' lived experiences as a voice to educate new stroke patients and the health professional staff who will care for them. The aim of the initial Quality Improvement project at a West Australian Stroke Rehabilitation Unit (SRU) was to co-produce a reflective learning resource with stroke patients and their families to help navigate the stroke recovery journey. A series of artefacts (documentary-style photographs, audio-narrated vignettes, MRI images and poetry) were collected from four stroke patients and their families at differing stages of recovery over 12 months as they recounted the honest and raw reality of what life is really like following a stroke. These artefacts were used in a pilot qualitative project to explore new stroke patients, their families and SRU health professional staff perceptions towards the artefacts in order to inform the final educational resource. These findings enhance our understandings of how we can use art and patient (healthcare consumers) voice to widen the lens of stroke recovery and provides a valuable template to co-produce peer-to-peer and health professions education reflective learning resources to promote more human- centred approaches to care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Tracking the localization and mobility of individual proteins in live cells is key for understanding how they mediate their function. Such information can be obtained from single molecule imaging techniques including as Single Particle Tracking (SPT) and Single Molecule Localization Microscopy (SMLM). Genetic code expansion (GCE) combined with bioorthogonal chemistry offers an elegant approach for direct labeling of proteins with fluorescent dyes, holding great potential for improving protein labeling in single molecule applications. Here we calibrated conditions for performing SPT and live-SMLM of bioorthogonally labeled plasma membrane proteins in live mammalian cells. Using SPT, the diffusion of bioorthogonally labeled EGF receptor and the prototypical Shaker voltage-activated potassium channel (Kv) was measured and characterized. Applying live-SMLM to bioorthogonally labeled Shaker Kv channels enabled visualizing the plasma membrane distribution of the channel over time with ∼30 nm accuracy. Finally, by competitive labeling with two Fl-dyes, SPT and live-SMLM were performed in a single cell and both the density and dynamics of the EGF receptor were measured at single molecule resolution in subregions of the cell. We conclude that GCE and bioorthogonal chemistry is a highly suitable, flexible approach for protein labeling in quantitative single molecule applications that outperforms current protein live-cell labeling approaches.

Synaptotagmin-1 (Syt1) is a calcium sensor protein that is critical for neurotransmission and is therefore extensively studied. Here, we use pairs of optically trapped beads coated with SNARE-free synthetic membranes to investigate Syt1-induced membrane remodeling. This activity is compared with that of Doc2b, which contains a conserved C 2 AB domain and induces membrane tethering and hemifusion in this cell-free model. We find that the soluble C 2 AB domain of Syt1 strongly affects the probability and strength of membrane-membrane interactions in a strictly Ca 2+ - and protein-dependent manner. Single-membrane loading of Syt1 yielded the highest probability and force of membrane interactions, whereas in contrast, Doc2b was more effective after loading both membranes. A lipid-mixing assay with confocal imaging reveals that both Syt1 and Doc2b are able to induce hemifusion; however, significantly higher Syt1 concentrations are required. Consistently, both C 2 AB fragments cause a reduction in the membrane-bending modulus, as measured by a method based on atomic force microscopy. This lowering of the energy required for membrane deformation may contribute to Ca 2+ -induced fusion., (Copyright © 2019 Biophysical Society. All rights reserved.)

Background: Sulfur-containing compounds represent an important class of chemical compounds due to their wide range of biological and pharmaceutical properties. Moreover, sulfur-containing compounds may be applied in other fields, such as biological, organic, and materials chemistry. Several studies on the activities of sulfur compounds have already proven their anti-inflammatory properties and use to treat diseases, such as Alzheimer's, Parkinson's, and HIV. Moreover, examples of sulfur-containing compounds include dapsone, quetiapine, penicillin, probucol, and nelfinavir, which are important drugs with known activities., Objective: This review will focus on the synthesis and application of some sulfur-containing compounds used to treat several diseases, as well as promising new drug candidates., Conclusion: Due to the variety of compounds containing C-S bonds, we have reviewed the different synthetic routes used toward the synthesis of sulfur-containing drugs and other compounds., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Type II Congenital Disorders of Glycosylation (CDG-II) are a group of diseases with challenging diagnostics characterized by defects in the processing of glycans in the Golgi apparatus. Mass Spectrometry (MS) has been a valuable tool in the definition of CDG-II subtypes. While some CDG-II subtypes are associated with specific N-glycan structures, others only produce changes in relative levels, reinforcing the demand for quantification methods., Methods: Plasma samples from control individuals were pooled, derivatized with deuterated iodomethane (I-CD 3 ), and used as internal standards for controls and patients whose glycans were derivatized with iodomethane (I-CH 3 ), followed by MALDI MS, LC-MS and -MS/MS analyses., Results: Total N-glycans from fifteen CDG-II patients were evaluated, and 4 cases with molecular diagnosis were considered in detail: 2ATP6V0A2-CDG siblings, and 2 MAN1B1-CDG patients, one of them carrying a previously undescribed p.Gly536Val mutation., Conclusions: Our methodology offers a feasible alternative to the current methods for CDG-II diagnosis by MS, which quantify glycan structures as fractions of the total summed signal across a mass spectrum, a strategy that lowers the variability of minor components. Moreover, given its sensitivity for less concentrated yet biologically relevant structures, it might assist the uncovering of novel diagnostic glycans in other CDG-II subtypes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Pharmacogenomic studies have shown that ADCY9 genotype determines the effects of the CETP (cholesteryl ester transfer protein) inhibitor dalcetrapib on cardiovascular events and atherosclerosis imaging. The underlying mechanisms responsible for the interactions between ADCY9 and CETP activity have not yet been determined., Methods: Adcy9-inactivated ( Adcy9 Gt/Gt ) and wild-type (WT) mice, that were or not transgenic for the CETP gene (CETPtg Adcy9 Gt/Gt and CETPtg Adcy9 WT ), were submitted to an atherogenic protocol (injection of an AAV8 [adeno-associated virus serotype 8] expressing a PCSK9 [proprotein convertase subtilisin/kexin type 9] gain-of-function variant and 0.75% cholesterol diet for 16 weeks). Atherosclerosis, vasorelaxation, telemetry, and adipose tissue magnetic resonance imaging were evaluated., Results: Adcy9 Gt/Gt mice had a 65% reduction in aortic atherosclerosis compared to WT ( P<0.01). CD68 (cluster of differentiation 68)-positive macrophage accumulation and proliferation in plaques were reduced in Adcy9 Gt/Gt mice compared to WT animals ( P<0.05 for both). Femoral artery endothelial-dependent vasorelaxation was improved in Adcy9 Gt/Gt mice (versus WT, P<0.01). Selective pharmacological blockade showed that the nitric oxide, cyclooxygenase, and endothelial-dependent hyperpolarization pathways were all responsible for the improvement of vasodilatation in Adcy9 Gt/Gt ( P<0.01 for all). Aortic endothelium from Adcy9 Gt/Gt mice allowed significantly less adhesion of splenocytes compared to WT ( P<0.05). Adcy9 Gt/Gt mice gained more weight than WT with the atherogenic diet; this was associated with an increase in whole body adipose tissue volume ( P<0.01 for both). Feed efficiency was increased in Adcy9 Gt/Gt compared to WT mice ( P<0.01), which was accompanied by prolonged cardiac RR interval ( P<0.05) and improved nocturnal heart rate variability ( P=0.0572). Adcy9 inactivation-induced effects on atherosclerosis, endothelial function, weight gain, adipose tissue volume, and feed efficiency were lost in CETPtg Adcy9 Gt/Gt mice ( P>0.05 versus CETPtg Adcy9 WT )., Conclusions: Adcy9 inactivation protects against atherosclerosis, but only in the absence of CETP activity. This atheroprotection may be explained by decreased macrophage accumulation and proliferation in the arterial wall, and improved endothelial function and autonomic tone.

A large number of studies demonstrate that cell mechanics and pathology are intimately linked. In particular, deformability of red blood cells (RBCs) is key to their function and is dramatically altered in the time course of diseases such as anemia and malaria. Due to the physiological importance of cell mechanics, many methods for cell mechanical probing have been developed. While single-cell methods provide very valuable information, they are often technically challenging and lack the high data throughput needed to distinguish differences in heterogeneous populations, while fluid-flow high-throughput methods miss the accuracy to detect subtle differences. Here we present a new method for multiplexed single-cell mechanical probing using acoustic force spectroscopy (AFS). We demonstrate that mechanical differences induced by chemical treatments of known effect can be measured and quantified. Furthermore, we explore the effect of extracellular vesicles (EVs) uptake on RBC mechanics and demonstrate that EVs uptake increases RBC deformability. Our findings demonstrate the ability of AFS to manipulate cells with high stability and precision and pave the way to further new insights into cellular mechanics and mechanobiology in health and disease, as well as potential biomedical applications.

We conducted a systematic review of literature on the residual effects of grain legumes in cereal-based systems of sub-Saharan Africa (SSA) to quantify the magnitude and variability of rotational effects, to explore the importance of environmental and management factors in determining variability and to evaluate the evidence of the different mechanisms that explain rotational effects. We retrieved 44 unique publications providing 199 observations comparing continuous cereal performance with that of a grain legume-cereal rotation. The overall mean yield increase of 0.49 t grain ha -1 , equal to an increase of 41% of the continuous cereal yield, is highly significant, but the variability in residual effects is large. Effects were more pronounced in southern Africa, the highlands of East Africa and the Guinea savannah, and less in the humid forest/derived savannah of West Africa and the Sudano-Sahelian zone. Maize showed stronger yield responses after a legume than millet and sorghum. Agro-ecological zone and cereal type were however confounded. All grain legume types significantly improved cereal yields, with stronger residual effects observed after soybean and groundnut than after cowpea. Fertiliser N application to cereals reduces the residual effects of legumes, but the response at 60-120 kg N ha -1 still equalled 0.32 t ha -1 or 59% of the response when no N is applied. The sustained benefits with large N applications indicate the importance of non-N effects. While mechanisms for improved soil P availability after grain legumes have been studied in some detail, it remains uncertain how important these are in farmers' fields. Grain legumes are unlikely to have a major influence on the availability of nutrients other than N and P, or on soil pH. Beneficial impacts of grain legumes on soil organic matter content can occur if legumes contribute to a greater overall cropping productivity, but studies generally report no such impacts. Evidence of impacts of grain legumes on weeds is limited to striga. Studies on the impacts on nematode pressure in cereals are inconclusive, probably because legumes act as a host for some of the key nematode genera that harm maize. The impact on the pressure of other pests and diseases in cereals is probably important, but evidence on this from SSA is lacking. Future research on N 2 -fixation by grain legumes and residual N benefits should focus on explaining the wide variability observed among sites. There is a clear need for more detailed mechanistic studies to assess the occurrence and relevance of non-N effects of grain legumes, particularly in relation to common pests and diseases in cereals.

Mature proteins can act as potential sources of encrypted bioactive peptides that, once released from their parent proteins, might interact with diverse biomolecular targets. In recent work we introduced a systematic methodology to uncover encrypted intragenic antimicrobial peptides (IAPs) within large protein sequence libraries. Given that such peptides may interact with membranes in different ways, resulting in distinct observable outcomes, it is desirable to develop a predictive methodology to categorize membrane active peptides and establish a link to their physicochemical properties. Building upon previous work, we explored the interaction of a range of IAPs with model membranes probed by differential scanning calorimetry (DSC) and circular dichroism (CD) techniques. The biophysical data were submitted to multivariate statistical methods and resulting peptide clusters were correlated to peptide structure and to their antimicrobial activity. A re-evaluation of the physicochemical properties of the peptides was conducted based on peptide cluster memberships. Our data indicate that membranolytic peptides produce characteristic thermal transition (DSC) profiles in model vesicles and that this can be used to categorize novel molecules with unknown biological activity. Incremental expansion of the model presented here might result in a unified experimental framework for the prediction of novel classes of membrane active peptides.

Examples of bioactive peptides derived from internal sequences of proteins are known for decades. The great majority of these findings appear to be fortuitous rather than the result of a deliberate and methodological-based enterprise. In the present work, we describe the identification and the biological activities of novel antimicrobial peptides unveiled as internal fragments of various plant proteins founded on our hypothesis-driven search strategy. All putative encrypted antimicrobial peptides were selected based upon their physicochemical properties that were iteratively selected by an in-house computer program named Kamal. The selected peptides were chemically synthesized and evaluated for their interaction with model membranes. Sixteen of these peptides showed antimicrobial activity against human and/or plant pathogens, some with a wide spectrum of activity presenting similar or superior inhibition efficacy when compared to classical antimicrobial peptides (AMPs). These original and previously unforeseen molecules constitute a broader and undisputable set of evidences produced by our group that illustrate how the intragenic concept is a workable reality and should be carefully explored not only for microbicidal agents but also for many other biological functions.

Objective: Integrating arts and humanities-based pedagogy into curricula is of growing interest among medical educators, particularly how it promotes reflection and empathy. Our aim was to explore whether a 2.50 min film titled 'The Art of the ED' stimulated reflective learning processes in a group of first year medical students., Methods: The film was shown prior to their first clinical placement in an ED. Student participation was voluntary and not assessable. Using an exploratory qualitative research approach, this study drew on data collected from students' individual written reflections, exploring their perceptions towards clinical experience in an emergency medicine (EM) attachment., Results: A total of 123 (51% of 240) students submitted a reflection. The qualitative data revealed three main themes: the opportunity for students to preview EM ('While watching the film, I felt like I was the patient and the doctor all at once, in that I was living the experience both from within and as an observer …'); exposed the reality of ED; and fostered a growing awareness of the fragility of human life., Conclusions: These findings highlight how visual methodologies (like film) create a safe, non-threatening space to access, experience and process emotion around their perceptions towards EM, and to anticipate and emotionally prepare for their impending clinical experience in the ED. These data support the use of visual methodologies to foster reflective processes that assist medical students to integrate the 'art' of EM, and the development and commitment of core doctoring values of empathy, service and respect for patients., (© 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.)

Inhibition of cholesteryl ester transfer protein (CETP) increases HDL cholesterol (HDL-C) levels. However, the circulating CETP level varies and the impact of its inhibition in species with high CETP levels on HDL structure and function remains poorly characterized. This study investigated the effects of dalcetrapib and anacetrapib, the two CETP inhibitors (CETPis) currently being tested in large clinical outcome trials, on HDL particle subclass distribution and cholesterol efflux capacity of serum in rabbits and monkeys. New Zealand White rabbits and vervet monkeys received dalcetrapib and anacetrapib. In rabbits, CETPis increased HDL-C, raised small and large α-migrating HDL, and increased ABCA1-induced cholesterol efflux. In vervet monkeys, although anacetrapib produced similar results, dalcetrapib caused opposite effects because the LDL-C level was increased by 42% and HDL-C decreased by 48% ( P < 0.01). The levels of α- and preβ-HDL were reduced by 16% ( P < 0.001) and 69% ( P < 0.01), resulting in a decrease of the serum cholesterol efflux capacity. CETPis modulate the plasma levels of mature and small HDL in vivo and consequently the cholesterol efflux capacity. The opposite effects of dalcetrapib in different species indicate that its impact on HDL metabolism could vary greatly according to the metabolic environment., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)

Nanoparticles (NPs) which enter physiological fluids are rapidly coated by proteins, forming a so-called corona which may strongly modify their interaction with tissues and cells relative to the bare NPs. In this work the interactions between a living cell and a nano-object, and in particular the effect on this of the adsorption of serum proteins, are directly examined by measuring the forces arising as an Atomic Force Microscope tip (diameter 20 nm) - simulating a nano-object - approaches and contacts a cell. We find that the presence of a serum protein corona on the tip strongly modifies the interaction as indicated by pronounced increase in the indentation, hysteresis and work of adhesion compared to a bare tip. Classically one expects an AFM tip interacting with a cell surface to be repelled due to cell elastic distortion, offset by tip-cell adhesion, and indeed such a model fits the bare-tip/cell interaction, in agreement with earlier work. However, the force plots obtained with serum-modified tips are very different, indicating that the cell is much more compliant to the approaching tip. The insights obtained in this work may promote better design of NPs for drug delivery and other nano-medical applications.

Research on sensorial interactions with psychiatric diseases and particularly with the depressive syndrome has mainly focused on visual or auditory processes and much less on olfaction. The depressive illness is one of the most frequent psychiatric diagnoses in the community, with approximately one in five women and one in eight men experiencing a major depressive episode during their lifetime. Although genetic, epigenetic, neuroanatomical, neurochemical, neuroendocrinological and neuroimmunological changes can be detected during depression, the etiology of depression remains partly unclear. The current explanatory models are based on two main factors, i.e. pharmacological dysfunctions and stress effects. In this way and because of strong connections between olfactory pathways and cerebral areas implied in mood regulation and emotions (i.e. the limbic system and prefrontal areas), the interactions between olfaction and depression could constitute a relevant way of research at three different levels. First, olfactory dysfunction observed in depression could serve the diagnosis and contribute to a better understanding of mechanisms implied in thymic pathologies. Published papers show a decrease of olfactory sensitivity in major depression which does not occur in bipolar or saisonal depression. Second, it has been shown that olfactory deficits could induce depressive symptoms. In this context, an animal model (olfactory bulbectomized rat) reinforces the hypothesis of the important role of olfaction in depression based on neuroanatomical and neurochemical observations. Third, several publications have demonstrated that odors can positively impact the depressive mood. Thus, a remediation by odors in depression appears to be a promising way. From several decades, the olfaction/depression interactions have been covered by a broad literature. Thus, the present review will not propose an exhaustive examination but aims to point out the most recently published papers and highlight their contributions to the understanding of olfactory processes implied in depression., (Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

The black-eyed pea trypsin/chymotrypsin inhibitor (BTCI) forms concentration dependent homomultimers, as previously demonstrated by Light scattering and Atomic Force Microscopy. Considering that these self-aggregates might influence their binding to cognate enzymes, we investigated the interaction of BTCI at picomolar concentrations using surface immobilized Chymotrypsin (α-CT) and Trypsin (T) by Surface Plasmon Resonance. Our results indicate that BTCI has subnanomolar affinity to both immobilized enzymes, which is approximately two orders of magnitude higher than previously reported. Moreover, we probed the influence of temperature on protein binding equilibria in order to investigate their interaction energetics. While the BTCI/T interaction concurs with the canonical entropy-driven mechanism described for BBI interactions with serine proteinases, the BTCI/α-CT interaction does not. Our measurements indicate that bimolecular BTCI/α-CT complexes form with a negative enthalpy change and a moderate entropic increase. Direct calorimetric evaluation is in accord with the van't Hoff approximation obtained by SPR. We demonstrate that as protein concentrations increase to the micromolar range, secondary endothermic events become prevalent and affect both the kinetics and thermodynamics of protein associations. Our study reinforces that BBI interactions with serine proteinases should be studied in dilute solutions to abridge often neglected secondary interactions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: High-density lipoproteins (HDL) favorably affect endothelial progenitor cells (EPC). Circulating progenitor cell level and function are impaired in patients with acute coronary syndrome (ACS). This study investigates the short-term effects of reconstituted HDL (rHDL) on circulating progenitor cells in patients with ACS., Methods and Findings: The study population consisted of 33 patients with recent ACS: 20 patients from the ERASE trial (randomized to receive 4 weekly intravenous infusions of CSL-111 40 mg/kg or placebo) and 13 additional patients recruited as controls using the same enrolment criteria. Blood was collected from 16 rHDL (CSL-111)-treated patients and 17 controls at baseline and at 6-7 weeks (i.e. 2-3 weeks after the fourth infusion of CSL-111 in ERASE). CD34+ and CD34+/kinase insert domain receptor (KDR+) progenitor cell counts were analyzed by flow cytometry. We found preserved CD34+ cell counts in CSL-111-treated subjects at follow-up (change of 1.6%), while the number of CD34+ cells was reduced (-32.9%) in controls (p = 0.017 between groups). The level of circulating SDF-1 (stromal cell-derived factor-1), a chemokine involved in progenitor cell recruitment, increased significantly (change of 21.5%) in controls, while it remained unchanged in CSL-111-treated patients (p = 0.031 between groups). In vitro exposure to CSL-111 of early EPC isolated from healthy volunteers significantly increased CD34+ cells, reduced early EPC apoptosis and enhanced their migration capacity towards SDF-1., Conclusions: The relative increase in circulating CD34+ cells and the low SDF-1 levels observed following rHDL infusions in ACS patients point towards a role of rHDL in cardiovascular repair mechanisms., Competing Interests: The compound used in the present study was a gift of CSL Limited (Parkville, Australia). We confirm that this commercial funding does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: In changing higher education environments, medical educators are increasingly challenged to prepare new doctors to care for ageing populations. The Depth of Field: Exploring Ageing resource (DOF) uses photographs, reflective questioning prompts, older adults' narratives and collaborative dialogue to foster anticipatory reflection or 'preflection' in medical students prior to their first geriatric medicine clinical placement. The aim of this research is to explore whether photographs, narratives and small group collaborative dialogue fosters reflective learning, enhances reflective capacity and has the potential to shift medical students' attitudes towards caring for older adults., Methods: This study used a mixed method evaluation design, measuring attitudes using pre and post questionnaire responses and individual written reflections drawn from 128 second year medical students, exploring their perceptions toward older adults., Results: Quantitative and qualitative data indicated that the DOF session generated reflective learning that resulted in positive shifts in medical students' perceptions towards older adults. The qualitative reflections were captured in four main themes: the opportunity provided to Envision working with older adults; the Tension created to challenge learners' misinformed assumptions, and the work of Dismantling those assumptions, leading to Seeing older people as individuals., Conclusions: These findings highlight how visual and narrative methodologies can be used as an effective reflective learning tool to challenge medical students' assumptions around ageing and how these may influence their care of older adults.