Can nurses rise to the public health challenge? How a novel solution in nurse education can address this contemporary question.

This paper raises the problem of how improvements in health outcomes, a key component in many governments' strategies, can be achieved. The work highlights a novel undergraduate educational approach which offers solutions to public health challenges within nursing. Against the backdrop of one UK university institution it discusses approaches that can guide nursing students towards a deeper understanding and engagement within the principles of public health. It then proposes how nurses can use their learning to become leaders of health improvement

Dynamic surfaces for the study Of mesenchymal stem cell growth through adhesion regulation

Out of their niche environment, adult stem cells, such as mesenchymal stem cells (MSCs), spontaneously differentiate. This makes both studying these important regenerative cells and growing large numbers of stem cells for clinical use challenging. Traditional cell culture techniques have fallen short of meeting this challenge, but materials science offers hope. In this study, we have used emerging rules of managing adhesion/cytoskeletal balance to prolong MSC cultures by fabricating controllable nanoscale cell interfaces using immobilized peptides that may be enzymatically activated to change their function. The surfaces can be altered (activated) at will to tip adhesion/cytoskeletal balance and initiate differentiation, hence better informing biological mechanisms of stem cell growth. Tools that are able to investigate the stem cell phenotype are important. While large phenotypical differences, such as the difference between an adipocyte and an osteoblast, are now better understood, the far more subtle differences between fibroblasts and MSCs are much harder to dissect. The development of technologies able to dynamically navigate small differences in adhesion are critical in the race to provide regenerative strategies using stem cells

Nanotopography controls cell cycle changes involved with skeletal stem cell self-renewal and multipotency

In culture isolated bone marrow mesenchymal stem cells (more precisely termed skeletal stem cells, SSCs) spontaneously differentiate into fibroblasts, preventing the growth of large numbers of multipotent SSCs for use in regenerative medicine. However, the mechanisms that regulate the expansion of SSCs, while maintaining multipotency and preventing fibroblastic differentiation are poorly understood. Major hurdles to understanding how the maintenance of SSCs is regulated are (a) SSCs isolated from bone marrow are heterogeneous populations with different proliferative characteristics and (b) a lack of tools to investigate SSC number expansion and multipotency. Here, a nanotopographical surface is used as a tool that permits SSC proliferation while maintaining multipotency. It is demonstrated that retention of SSC phenotype in culture requires adjustments to the cell cycle that are linked to changes in the activation of the mitogen activated protein kinases. This demonstrates that biomaterials can offer cross-SSC culture tools and that the biological processes that determine whether SSCs retain multipotency or differentiate into fibroblasts are subtle, in terms of biochemical control, but are profound in terms of determining cell fat

Responsive cell–material interfaces

Major design aspects for novel biomaterials are driven by the desire to mimic more varied and complex properties of a natural cellular environment with man-made materials. The development of stimulus responsive materials makes considerable contributions to the effort to incorporate dynamic and reversible elements into a biomaterial. This is particularly challenging for cell–material interactions that occur at an interface (biointerfaces); however, the design of responsive biointerfaces also presents opportunities in a variety of applications in biomedical research and regenerative medicine. This review will identify the requirements imposed on a responsive biointerface and use recent examples to demonstrate how some of these requirements have been met. Finally, the next steps in the development of more complex biomaterial interfaces, including multiple stimuli-responsive surfaces, surfaces of 3D objects and interactive biointerfaces will be discussed

Nanopatterned titanium implants accelerate bone formation in vivo

Accelerated de novo formation of bone is a highly desirable aim of implants targeting musculoskeletal injuries. To date, this has primarily been addressed by biologic factors. However, there is an unmet need for robust, highly reproducible yet economic alternative strategies that strongly induce an osteogenic cell response. Here, we present a surface engineering method of translating bioactive nanopatterns from polymeric in vitro studies to clinically relevant material for orthopedics: three-dimensional, large area metal. We use a titanium-based sol–gel whereby metal implants can be engineered to induce osteoinduction both in vitro and in vivo. We show that controlled disordered nanotopographies presented as pillars with 15–25 nm height and 100 nm diameter on titanium dioxide effectively induce osteogenesis when seeded with STRO-1-enriched human skeletal stem cells in vivo subcutaneous implantation in mice. After 28 days, samples were retrieved, which showed a 20-fold increase in osteogenic gene induction of nanopatterned substrates, indicating that the sol–gel nanopatterning method offers a promising route for translation to future clinical orthopedic implants

Randomized, Controlled Trial Evaluating a Baby Wash Product on Skin Barrier Function in Healthy, Term Neonates

Objectives To examine the hypothesis that the use of a wash product formulated for newborn (<1 month of age) bathing is not inferior (no worse) to bathing with water only. Design Assessor‐blinded, randomized, controlled, noninferiority trial. Setting A teaching hospital in the Northwest of England and in participants’ homes. Participants Three‐hundred‐and‐seven healthy, term infants recruited within 48 hours of birth. Method We compared bathing with a wash product (n = 159) to bathing with water alone (n = 148). The primary outcome was transepidermal water loss (TEWL) at 14 days postbirth; the predefined difference deemed to be unimportant was 1.2. Secondary outcomes comprised changes in stratum corneum hydration, skin surface pH, clinical observations of the skin, and maternal views. Results Complete TEWL data were obtained for 242 (78.8%) infants. Wash was noninferior to water alone in terms of TEWL (intention‐to‐treat analysis: 95% confidence interval [CI] for difference [wash–water, adjusted for family history of eczema, neonate state, and baseline] −1.24, 1.07; per protocol analysis: 95% CI −1.42, 1.09). No significant differences were found in secondary outcomes. Conclusion We were unable to detect any differences between the newborn wash product and water. These findings provide reassurance to parents who choose to use the test newborn wash product or other technically equivalent cleansers and provide the evidence for health care professionals to support parental choice

Nanotopography reveals metabolites that maintain the immunomodulatory phenotype of mesenchymal stromal cells

Mesenchymal stromal cells (MSCs) are multipotent progenitor cells that are of considerable clinical potential in transplantation and anti-inflammatory therapies due to their capacity for tissue repair and immunomodulation. However, MSCs rapidly differentiate once in culture, making their large-scale expansion for use in immunomodulatory therapies challenging. Although the differentiation mechanisms of MSCs have been extensively investigated using materials, little is known about how materials can influence paracrine activities of MSCs. Here, we show that nanotopography can control the immunomodulatory capacity of MSCs through decreased intracellular tension and increasing oxidative glycolysis. We use nanotopography to identify bioactive metabolites that modulate intracellular tension, growth and immunomodulatory phenotype of MSCs in standard culture and during larger scale cell manufacture. Our findings demonstrate an effective route to support large-scale expansion of functional MSCs for therapeutic purposes

Mutations in TOP3A Cause a Bloom Syndrome-like Disorder

Bloom syndrome, caused by biallelic mutations in BLM, is characterized by prenatal-onset growth deficiency, short stature, an erythematous photosensitive malar rash, and increased cancer predisposition. Diagnostically, a hallmark feature is the presence of increased sister chromatid exchanges (SCEs) on cytogenetic testing. Here, we describe biallelic mutations in TOP3A in ten individuals with prenatal-onset growth restriction and microcephaly. TOP3A encodes topoisomerase III alpha (TopIIIα), which binds to BLM as part of the BTRR complex, and promotes dissolution of double Holliday junctions arising during homologous recombination. We also identify a homozygous truncating variant in RMI1, which encodes another component of the BTRR complex, in two individuals with microcephalic dwarfism. The TOP3A mutations substantially reduce cellular levels of TopIIIα, and consequently subjects’ cells demonstrate elevated rates of SCE. Unresolved DNA recombination and/or replication intermediates persist into mitosis, leading to chromosome segregation defects and genome instability that most likely explain the growth restriction seen in these subjects and in Bloom syndrome. Clinical features of mitochondrial dysfunction are evident in several individuals with biallelic TOP3A mutations, consistent with the recently reported additional function of TopIIIα in mitochondrial DNA decatenation. In summary, our findings establish TOP3A mutations as an additional cause of prenatal-onset short stature with increased cytogenetic SCEs and implicate the decatenation activity of the BTRR complex in their pathogenesis

Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma

Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE