Cryogels Based on Poly(2-oxazoline)s through Development of Bi- and Trifunctional Cross-Linkers Incorporating End Groups with Adjustable Stability.

1,4-Bis(iodomethyl)benzene and 1,3,5-tris(iodomethyl)benzene were used as initiators for the cationic ring-opening polymerization (CROP) of 2-ethyl-2-oxazoline (EtOx) and its copolymerization with tert-butyl (3-(4,5-dihydrooxazol-2-yl)propyl)carbamate (BocOx) or methyl 3-(4,5-dihydrooxazol-2-yl)propanoate (MestOx). Kinetic studies confirmed the applicability of these initiators. Termination with suitable nucleophiles resulted in two- and three-armed cross-linkers featuring acrylate, methacrylate, piperazine-acrylamide, and piperazine-methacrylamide as polymerizable ω-end groups. Matrix-assisted laser desorption/ionization mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy confirmed the successful attachment of the respective ω-end groups at all initiation sites for every prepared cross-linkers. Except for acrylate, each ω-end group remained stable during deprotection of BocOx containing cross-linkers. The cryogels were prepared using EtOx-based cross-linkers, as confirmed by solid-state NMR spectroscopy, scanning electron microscopy, and thermogravimetric analysis. Stability tests revealed a complete dissolution of the acrylate-containing gels at pH = 14, whereas the piperazine-acrylamide-based cryogels featured excellent hydrolytic stability.

Stenotrophomonas maltophilia affects the gene expression profiles of the major pathogens Pseudomonas aeruginosa and Staphylococcus aureus in an in vitro multispecies biofilm model.

IMPORTANCE: In the past, studies have focused on bacterial pathogenicity in mono-species infections, in part ignoring the clinical relevance of diseases caused by more than one pathogen (i.e., polymicrobial infections). However, it is now common knowledge that multiple bacteria species are often involved in the course of an infection. For treatment of such infections, it is absolutely important to understand the dynamics of species interactions at possible infection sites and the molecular mechanisms behind these interactions. Here, we studied the impact of Stenotrophomonas maltophilia on its commensals Pseudomonas aeruginosa and Staphylococcus aureus in multispecies biofilms. We analyzed the 3D structural architectures of dual- and triple-species biofilms, niche formation within the biofilms, and the interspecies interactions on a molecular level. RNAseq data identified key genes involved in multispecies biofilm formation and interaction as potential drug targets for the clinical combat of multispecies infection with these major pathogens.

Modification of Branched Poly(ethylene imine) with d-Fructose for Selective Delivery of siRNA into Human Breast Cancer Cells.

Branched poly(ethylene imine) (bPEI) is frequently used in RNA interference (RNAi) experiments as a cationic polymer for the delivery of small interfering RNA (siRNA) because of its ability to form stable polyplexes that facilitate siRNA uptake. However, the use of bPEI in gene delivery is limited by its cytotoxicity and a need for target specificity. In this work, bPEI is modified with d-fructose to improve biocompatibility and target breast cancer cells through the overexpressed GLUT5 transporter. Fructose-substituted bPEI (Fru-bPEI) is accessible in three steps starting from commercially available protected fructopyranosides and bPEI. Several polymers with varying molecular weights, degrees of substitution, and linker positions on d-fructose (C1 and C3) are synthesized and characterized with NMR spectroscopy, size exclusion chromatography, and elemental analysis. In vitro biological screenings show significantly reduced cytotoxicity of 10 kDa bPEI after fructose functionalization, specific uptake of siRNA polyplexes, and targeted knockdown of green fluorescent protein (GFP) in triple-negative breast cancer cells (MDA-MB-231) compared to noncancer cells (HEK293T).

"Dealing with the Hospital has Become too Difficult for Us to Do Alone" - Developing an Integrated Care Program for Children with Medical Complexity (CMC).

INTRODUCTION: Children with medical complexity (CMC) require highly specialised care, often from multiple providers and over many years. This paper describes the first 18 months of development of the Kids Guided Personalised Services (GPS) Integrated Care Program (the Program). This Program aims to improve health care experience; communication and to streamline provision of care. DISCUSSION: Key enablers across the Program were put in place and 5 individual project streams were used to implement change. An extensive formative evaluation process was undertaken to truly understand all perspectives in developing the Program. CONCLUSION/KEY LESSONS: This Program supports families who are caring for CMC by developing shared care models that bring together local health services with the tertiary hospitals. The methodology used has resulted in comprehensive system change and transformation; reduced presentations to the Emergency Department (ED), avoidable admissions and travel time. A challenge remains in meaningfully engaging primary health care providers.

A qualitative study of health care providers' perceptions and experiences of working together to care for children with medical complexity (CMC).

BACKGROUND: Children with medical complexity (CMC) have a wide range of long term health problems and disabilities that have an adverse impact on their quality of life. They have high levels of family identified health care needs and health care utilisation. There is no Australian literature on the experiences of health care providers working in the Australian tertiary, secondary and primary health care system, whilst managing CMC. This information is essential to inform the design of integrated health care systems for these children. We address this knowledge gap by exploring the perceptions and experiences of health care providers on the provision of health care for CMC aged 0 to 18 years. METHOD: A qualitative research study was undertaken. Stakeholder forums, group and individual in depth interviews were undertaken using a semi-structured interview guide. The stakeholder forums were audio recorded and transcribed verbatim. Field notes of the stakeholder forums, group and individual interviews were taken. Inductive thematic analysis was undertaken to identify key themes. RESULTS: One hundred and three providers took part in the stakeholder forums and interviews across 3 local health districts, a tertiary paediatric hospital network, and primary health care organisations. Providers expressed concern regarding family capacity to negotiate the system, which was impacted by the medical complexity of the children and psychosocial complexity of their families. Lack of health care provider capacity in terms of their skills, time and availability to manage CMC was also a key problem. These issues occurred within a health system that had impaired capacity in terms of fragmentation of care and limited communication among health care providers. CONCLUSION: When designing integrated care models for CMC, it is essential to understand and address the challenges experienced by their health care providers. This requires adequate training of providers, additional resources and time for coordination of care, improved systems of communication among services, with timely access to key information for parents and providers.

Theory of high-temperature multiferroicity in cupric oxide.

The incommensurate-commensurate phases reported in cupric oxide below 230 K are shown theoretically to realize an inverted sequence of symmetry-breaking mechanisms with respect to the usual sequence occurring in low-temperature multiferroic compounds. The sequence inversion results from a strong triggering-coupling mechanism between two antiferromagnetic order parameters inducing a first-order transition to the multiferroic phase. Such mechanism is favored by the large antiferromagnetic superexchange interactions, responsible of the high-T(N) temperature, and implies a preeminence of these interactions on the magnetocrystalline anisotropy. The magnetic structures of the equilibrium phases and the microscopic interactions giving rise to the polarization are determined.