Intermediate Care: The Role of Medicines Management

Healthcare systems worldwide are facing an unprecedented demographic change as globally, the number of older people will triple to 2 billion by the year 2050. The resulting pressures on acute services have been instrumental in the development of intermediate care (IC) as a new healthcare model, which has its origins in the National Health Service in the UK. IC is an umbrella term for patient services that do not require the resources of a general hospital but are beyond the scope of a traditional primary care team. IC aims to promote timely discharge from hospital, prevent unnecessary hospital admissions and reduce the need for long-term residential care by optimizing functional independence. Various healthcare providers around the world have adopted similar models of care to manage changing healthcare needs. Polypharmacy, along with age-related changes, places older people at an increased risk of adverse drug events, including inappropriate prescribing, which has been shown to be prevalent in this population in other healthcare settings. Medicines management (the practice of maximizing health through optimal use of medicines) of older people has been discussed in the literature in a variety of settings; however, its place within IC is largely unknown. Despite IC being a multidisciplinary healthcare model, there is a lack of evidence to suggest that enhanced pharmaceutical involvement is core to the service provided within IC. This review article highlights the gap in the literature surrounding medicines management within IC and identifies potential solutions aimed at improving patient outcomes in this setting.

Secreted Proteins from the Helminth Fasciola hepatica Inhibit the Initiation of Autoreactive T Cell Responses and Prevent Diabetes in the NOD Mouse

Infections with helminth parasites prevent/attenuate auto-inflammatory disease. Here we show that molecules secreted by a helminth parasite could prevent Type 1 Diabetes (T1D) in nonobese diabetic (NOD) mice. When delivered at 4 weeks of age (coincident with the initiation of autoimmunity), the excretory/secretory products of Fasciola hepatica (FhES) prevented the onset of T1D, with 84% of mice remaining normoglycaemic and insulitis-free at 30 weeks of age. Disease protection was associated with suppression of IFN-γ secretion from autoreactive T cells and a switch to the production of a regulatory isotype (from IgG2a to IgG1) of autoantibody. Following FhES injection, peritoneal macrophages converted to a regulatory M2 phenotype, characterised by increased expression levels of Ym1, Arg-1, TGFβ and PD-L1. Expression of these M2 genetic markers increased in the pancreatic lymph nodes and the pancreas of FhES-treated mice. In vitro, FhES-stimulated M2 macrophages induced the differentiation of Tregs from splenocytes isolated from naïve NOD mice. Collectively, our data shows that FhES contains immune-modulatory molecules that mediate protection from autoimmune diabetes via the induction and maintenance of a regulatory immune environment.

Bone morphogenetic proteins and their antagonists: current and emerging clinical uses

Bone morphogenetic proteins (BMPs) are members of the TGFβ superfamily of secreted cysteine knot proteins that includes TGFβ₁, nodal, activins and inhibins. BMPs were first discovered by Urist in the 1960s when he showed that implantation of demineralized bone into intramuscular tissue of rabbits induced bone and cartilage formation. Since this seminal discovery, BMPs have also been shown to play key roles in several other biological processes, including limb, kidney, skin, hair and neuronal development, as well as maintaining vascular homeostasis. The multifunctional effects of BMPs make them attractive targets for the treatment of several pathologies, including bone disorders, kidney and lung fibrosis, and cancer. This review will summarize current knowledge on the BMP signalling pathway and critically evaluate the potential of recombinant BMPs as pharmacological agents for the treatment of bone repair and tissue fibrosis in patients.

Failed filament eruption inside a coronal mass ejection in active region 11121

Aims. We study the formation and evolution of a failed filament eruption observed in NOAA active region 11121 near the southeast
limb on November 6, 2010.
Methods. We used a time series of SDO/AIA 304, 171, 131, 193, 335, and 94 Å images, SDO/HMI magnetograms, as well as ROSA
and ISOON Hα images to study the erupting active region.
Results. We identify coronal loop arcades associated with a quadrupolar magnetic configuration, and show that the expansion and
cancellation of the central loop arcade system over the filament is followed by the eruption of the filament. The erupting filament
reveals a clear helical twist and develops the same sign of writhe in the form of inverse γ-shape.
Conclusions. The observations support the “magnetic breakout” process in which the eruption is triggered by quadrupolar reconnection
in the corona. We propose that the formation mechanism of the inverse γ-shape flux rope is the magnetohydrodynamic helical
kink instability. The eruption has failed because of the large-scale, closed, overlying magnetic loop arcade that encloses the active
region

Enrichment of low-abundance proteins from bovine and porcine serum samples for proteomic studies

One of the main applications of serum proteomics is the identification of new biomarkers for animal disease or animal production. However, potential obstacles to these studies are the poor performance of affinity serum depletion methods based on human antigens when using animal samples, and loss of minor serum components bound to albumin and other proteins. In the present study, we have analyzed the efficiency and reproducibility of the ProteoMiner® beads with bovine and porcine serum samples, and compared to a traditional immunoaffinity-based albumin and IgG depletion system specific for human samples. The ProteoMiner kit is based on the use of a combinatorial peptide binding library and intends to enrich low-abundance proteins.

Elucidation of the Burkholderia cenocepacia hopanoid biosynthesis pathway uncovers functions for conserved proteins in hopanoid-producing bacteria

Hopanoids are bacterial surrogates of eukaryotic membrane sterols and among earth's most abundant natural products. Their molecular fossils remain in sediments spanning more than a billion years. However, hopanoid metabolism and function are not fully understood. Burkholderia species are environmental opportunistic pathogens that produce hopanoids and also occupy diverse ecological niches. We investigated hopanoids biosynthesis in Burkholderia cenocepacia by deletion mutagenesis and structural characterization of the hopanoids produced by the mutants. The enzymes encoded by hpnH and hpnG were essential for production of all C35 extended hopanoids, including bacteriohopanetetrol (BHT), BHT glucosamine and BHT cyclitol ether. Deletion of hpnI resulted in BHT production, while ΔhpnJ produced only BHT glucosamine. Thus, HpnI is required for BHT glucosamine production while HpnJ is responsible for its conversion to the cyclitol ether. The ΔhpnH and ΔhpnG mutants could not grow under any stress condition tested, whereas ΔhpnI, ΔhpnJ and ΔhpnK displayed wild-type growth rates when exposed to detergent, but varying levels of sensitivity to low pH and polymyxin B. This study not only elucidates the biosynthetic pathway of hopanoids in B. cenocepacia, but also uncovers a biosynthetic role for the conserved proteins HpnI, HpnJ and HpnK in other hopanoid-producing bacteria.whereas ΔhpnI, ΔhpnJ and ΔhpnK displayed wild-type growth rates when exposed to detergent, but varying levels of sensitivity to low pH and polymyxin B. This study not only elucidates the biosynthetic pathway of hopanoids in B. cenocepacia, but also uncovers a biosynthetic role for the conserved proteins HpnI, HpnJ and HpnK in other hopanoid-producing bacteria.

Mutations in the H, F, or M proteins can facilitate resistance of measles virus to neutralizing human anti-MV sera

Although there is currently no evidence of emerging strains of measles virus (MV) that can resist neutralization by the anti-MV antibodies present in vaccinees, certain mutations in circulating wt MV strains appear to reduce the efficacy of these antibodies. Moreover, it has been hypothesized that resistance to neutralization by such antibodies could allow MV to persist. In this study, we use a novel in vitro system to determine the molecular basis of MV's resistance to neutralization. We find that both wild-type and laboratory strain MV variants that escape neutralization by anti-MV polyclonal sera possess multiple mutations in their H, F, and M proteins. Cytometric analysis of cells expressing viral escape mutants possessing minimal mutations and their plasmid-expressed H, F, and M proteins indicates that immune resistance is due to particular mutations that can occur in any of these three proteins that affect at distance, rather than directly, the native conformation of the MV-H globular head and hence its epitopes. A high percentage of the escape mutants contain mutations found in cases of Subacute Sclerosing Panencephalitis (SSPE) and our results could potentially shed light on the pathogenesis of this rare fatal disease.

Composite materials based on silk proteins

A number of animals have evolved to produce silk-based composite materials for a variety of task-specific applications. The review initially focuses on the composite structure of silk fibers produced naturally by silkworms and spiders, followed by the preparation and applications of man-made composite materials (including fibers, films, foams, gels and particulates) incorporating silk proteins in combination with other polymers (both natural and synthetic) and/or inorganic particles.