The effect of self-sorting and co-assembly on the mechanical properties of low molecular weight hydrogels

Self-sorting in low molecular weight hydrogels can be achieved using a pH triggered approach. We show here that this method can be used to prepare gels with different types of mechanical properties. Cooperative, disruptive or orthogonal assembled systems can be produced. Gels with interesting behaviour can be also prepared, for example self-sorted gels where delayed switch-on of gelation occurs. By careful choice of gelator, co-assembled structures can also be generated, which leads to synergistic strengthening of the mechanical properties

GRADE-ADOLOPMENT process to develop 24-hour movement behavior recommendations and physical activity guidelines for the under 5s in the United Kingdom, 2019

Background: This article summarizes the approach taken to develop UK Chief Medical Officers' physical activity guidelines for the Under 5s, 2019. Methods: The Grading of Recommendations Assessment, Development and Evaluation (GRADE)- Adaptation, Adoption, De Novo Development (ADOLOPMENT) approach was used, based on the guidelines from Canada and Australia, with evidence updated to February 2018. Recommendations were based on the associations between (1) time spent in sleep, sedentary time, physical activity, and 10 health outcomes and (2) time spent in physical activity and sedentary behavior on sleep outcomes (duration and latency). Results: For many outcomes, more time spent in physical activity and sleep (up to a point) was beneficial, as was less time spent in sedentary behavior. The authors present, for the first time, evidence in GRADE format on behavior type-outcome associations for infants, toddlers, and preschoolers. Stakeholders supported all recommendations, but recommendations on sleep and screen time were not accepted by the Chief Medical Officers; UK guidelines will refer only to physical activity. Conclusions: This is the first European use of GRADE-ADOLOPMENT to develop physical activity guidelines. The process is robust, rapid, and inexpensive, but the UK experience illustrates a number of challenges that should help development of physical activity guidelines in future

Changing behaviour 'more or less'-do theories of behaviour inform strategies for implementation and de-implementation? A critical interpretive synthesis

BACKGROUND: Implementing evidence-based care requires healthcare practitioners to do less of some things (de-implementation) and more of others (implementation). Variations in effectiveness of behaviour change interventions may result from failure to consider a distinction between approaches by which behaviour increases and decreases in frequency. The distinction is not well represented in methods for designing interventions. This review aimed to identify whether there is a theoretical rationale to support this distinction. METHODS: Using Critical Interpretative Synthesis, this conceptual review included papers from a broad range of fields (biology, psychology, education, business) likely to report approaches for increasing or decreasing behaviour. Articles were identified from databases using search terms related to theory and behaviour change. Articles reporting changes in frequency of behaviour and explicit use of theory were included. Data extracted were direction of behaviour change, how theory was operationalised, and theory-based recommendations for behaviour change. Analyses of extracted data were conducted iteratively and involved inductive coding and critical exploration of ideas and purposive sampling of additional papers to explore theoretical concepts in greater detail. RESULTS: Critical analysis of 66 papers and their theoretical sources identified three key findings: (1) 9 of the 15 behavioural theories identified do not distinguish between implementation and de-implementation (5 theories were applied to only implementation or de-implementation, not both); (2) a common strategy for decreasing frequency was substituting one behaviour with another. No theoretical basis for this strategy was articulated, nor were methods proposed for selecting appropriate substitute behaviours; (3) Operant Learning Theory makes an explicit distinction between techniques for increasing and decreasing frequency. DISCUSSION: Behavioural theories provide little insight into the distinction between implementation and de-implementation. Operant Learning Theory identified different strategies for implementation and de-implementation, but these strategies may not be acceptable in health systems. Additionally, if behaviour substitution is an approach for de-implementation, further investigation may inform methods or rationale for selecting the substitute behaviour

Feasibility and Acceptability of the \u3cem\u3eMazi Umntanakho\u3c/em\u3e Digital Tool in South African Settings: A Qualitative Evaluation

To address the need for interventions targeting social emotional development and mental health of young children in South Africa, the Mazi Umntanakho (‘know your child’) digital tool was co-designed, and piloted with caregivers and 3–5-year-old children involved in home visiting programmes promoting early childhood development. The aim of this study was to qualitatively evaluate the feasibility and acceptability of this tool in four urban and four rural low-income communities, from the perspective of home visitors and caregivers. Focus groups were conducted with home visitors (n = 117) and caregivers (n = 72). Issues relating to the feasibility of implementing the tool included timing of using the tool, technical and social implementation challenges, WhatsApp as the preferred platform, and participants\u27 recommendations for future implementation. Overall, the tool was acceptable for home visitors and caregivers and was perceived to have a positive impact on children\u27s development, and the relationship between caregivers and children

Young Children’s Mental Well-Being in Low-Income South African Settings: A Qualitative Study

This qualitative study aimed to capture community perspectives of the risks and protective factors for social emotional development and mental health of young children in low-income South Africa settings, and was conducted as one component of a larger study with the ultimate aim of co-designing the Mazi Umntanakho (‘know your child’) digital tool. Twenty focus group discussions (n = 154, 97% female) were held with staff of community-based organisations (CBOs) and community health worker (CHW) programmes in urban and rural sites from four geographical regions. Data were analysed thematically, and grouped according to components of nurturing care (responsive caregiving, safety and security, good health, adequate nutrition, opportunities for early learning) and risk and protective factors. Risks reported by participants far outweighed protective factors, and the most dominant theme identified was risks associated with responsive caregiving from CBO and CHW perspectives. These related to participants’ perceptions of caregivers’ attitudes, knowledge, beliefs, behaviours, and challenges not conducive to the provision of responsive caregiving. The most commonly perceived risks to safety and security were substance abuse, along with economic challenges, neglect, abuse and violence. Basic needs not being met was reported as the main risk to adequate nutrition and good health, followed by insufficient services. Limited resources and caregivers’ limited education and literacy were perceived to be risks to early learning. These findings highlight the urgent need to mitigate risks and amplify protective factors for the social emotional development and mental health of young children in South Africa. It is critical that these are considered within the contextual realities of low-income communities

High-throughput characterisation of supramolecular gelation processes using a combination of optical density, fluorescence and UV-Vis absorption measurements

Herein, we showcase the use of high-throughput microplate reader methodologies for the characterisation of supramolecular gels. We demonstrate how UV-Vis absorption, optical density and fluorescence measurements can selectively define gel fibre assembly/ disassembly processes, casting a new light on the construction of these material

Diverse Bacteriocins Produced by Strains From the Human Milk Microbiota

Peer-reviewedMicrobial colonization of the infant gut is a convoluted process dependent on numerous contributing factors, including age, mode of delivery and diet among others that has lifelong implication for human health. Breast milk also contains a microbiome which acts as a source of colonizing bacteria for the infant. Here, we demonstrate that human milk harbors a wide diversity of bacteriocin-producing strains with the potential to compete among the developing gut microbiota of the infant. We screened 37 human milk samples and found isolates with antimicrobial activity and distinct cross-immunity profiles. From these isolates, we detected 73 putative gene clusters for bacteriocins of all known sub-classes, including 16 novel prepeptides. More specifically, we detected two novel lantibiotics, four sactibiotics and three class IIa bacteriocins with an unusual modification of the pediocin box that is composed of YDNGI instead of the highly conserved motif YGNGV. Moreover, we identified a novel class IIb bacteriocin, four novel class IIc and two class IId bacteriocins. In conclusion, human milk contains a variety of bacteriocin-producing strains which may provide them a competitive advantage in the colonization of the infant gut and suggests that the milk microbiota is a source of antimicrobial potential.Science Foundation Irelan

HealthKick: a nutrition and physical activity intervention for primary schools in low-income settings

<p>Abstract</p> <p>Background</p> <p>The burden of non-communicable diseases, including type 2 diabetes, is growing in South Africa. This country has a complex mix of over- and under-nutrition, especially in low-income communities, and concerning levels of physical inactivity in children and youth. This paper describes HealthKick, a school-based nutrition and physical activity intervention in primary schools in these settings aimed at reducing diabetes risk factors.</p> <p>Methods/Design</p> <p>This study includes schools within historically disadvantaged, low-income communities from an urban area close to the city of Cape Town and from two rural areas outside of Cape Town, South Africa. The three Educational Districts involved are Metropole North, Cape Winelands and the Overberg. The study has three phases: intervention mapping and formative assessment, intervention development, and outcome and process evaluation. Sixteen schools were purposively selected to participate in the study and randomly allocated as intervention (eight schools) and control (eight schools).</p> <p>The primary aims of HealthKick are to promote healthful eating habits and increase regular participation in health-enhancing physical activity in children, parents and teachers, to prevent overweight, and reduce risk of chronic diseases (particularly type 2 diabetes); as well as to promote the development of an environment within the school and community that facilitates the adoption of healthy lifestyles.</p> <p>The components of HealthKick are: action planning, toolkit (resource guide, a resource box and physical activity resource bin), and an Educators' Manual, which includes a curriculum component.</p> <p>Discussion</p> <p>This study continues to highlight the key role that educators play in implementing a school-based intervention, but that developing capacity within school staff and stakeholders is not a simple or easy task. In spite of the challenges experienced thus far, valuable findings are being produced from this study, especially from Phase 1. Materials developed could be disseminated to other schools in low-income settings both within and outside of South Africa. Owing to the novelty of the HealthKick intervention in low-income South African primary schools, the findings of the evaluation phase have the potential to impact on policy and practice within these settings.</p

Analyses of human vaccine-specific circulating and bone marrow-resident B cell populations reveal benefit of delayed vaccine booster dosing with blood-stage malaria antigens

We have previously reported primary endpoints of a clinical trial testing two vaccine platforms for the delivery of Plasmodium vivax malaria DBPRII: viral vectors (ChAd63, MVA), and protein/adjuvant (PvDBPII with 50µg Matrix-M™ adjuvant). Delayed boosting was necessitated due to trial halts during the pandemic and provides an opportunity to investigate the impact of dosing regimens. Here, using flow cytometry – including agnostic definition of B cell populations with the clustering tool CITRUS – we report enhanced induction of DBPRII-specific plasma cell and memory B cell responses in protein/adjuvant versus viral vector vaccinees. Within protein/adjuvant groups, delayed boosting further improved B cell immunogenicity compared to a monthly boosting regimen. Consistent with this, delayed boosting also drove more durable anti-DBPRII serum IgG. In an independent vaccine clinical trial with the P. falciparum malaria RH5.1 protein/adjuvant (50µg Matrix-M™) vaccine candidate, we similarly observed enhanced circulating B cell responses in vaccinees receiving a delayed final booster. Notably, a higher frequency of vaccine-specific (putatively long-lived) plasma cells was detected in the bone marrow of these delayed boosting vaccinees by ELISPOT and correlated strongly with serum IgG. Finally, following controlled human malaria infection with P. vivax parasites in the DBPRII trial, in vivo growth inhibition was observed to correlate with DBPRII-specific B cell and serum IgG responses. In contrast, the CD4+ and CD8+ T cell responses were impacted by vaccine platform but not dosing regimen and did not correlate with in vivo growth inhibition in a challenge model. Taken together, our DBPRII and RH5 data suggest an opportunity for protein/adjuvant dosing regimen optimisation in the context of rational vaccine development against pathogens where protection is antibody-mediated

Impact of COVID-19 in patients on active melanoma therapy and with history of melanoma

INTRODUCTION: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. RESULTS: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35). CONCLUSIONS: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors