Foodservice in hospital: development of a theoretical model for patient experience and satisfaction using one hospital in the UK National Health Service as a case study

Hospital foodservice does not operate in isolation but requires the cooperation and integration of several disciplines to provide the ultimate patient experience. The objective of this research was to explore the antecedents to patient satisfaction and experience, including the service element. Accordingly, focus groups were conducted with doctors (n = 4), nurses (n = 5), ward hostesses (n = 3) and patients together with their visitors (n = 10), while open-ended interviews were conducted with the foodservice manager, facilities manager, chief dietitian, orthopaedic ward dietitian and chief pharmacist. Themes centred on ‘patients’, ‘foodservice’ and ‘mealtimes’, and results show that food qualities, particularly temperature and texture, are important factors impinging on patient satisfaction, and the trolley system of delivery is an acceptable style of service. Service predisposition demonstrates little relevance to patient satisfaction towards overall meal enjoyment. A theoretical model has been developed that identifies hospital foodservice in a cyclic relationship with the community primary healthcare team

Sulfatase‐mediated manipulation of the astrocyte‐Schwann cell interface

Schwann cell (SC) transplantation following spinal cord injury (SCI) may have therapeutic potential. Functional recovery is limited however, due to poor SC interactions with host astrocytes and the induction of astrogliosis. Olfactory ensheathing cells (OECs) are closely related to SCs, but intermix more readily with astrocytes in culture and induce less astrogliosis. We previously demonstrated that OECs express higher levels of sulfatases, enzymes that remove 6‐O‐sulfate groups from heparan sulphate proteoglycans, than SCs and that RNAi knockdown of sulfatase prevented OEC‐astrocyte mixing in vitro. As human OECs are difficult to culture in large numbers we have genetically engineered SCs using lentiviral vectors to express sulfatase 1 and 2 (SC‐S1S2) and assessed their ability to interact with astrocytes. We demonstrate that SC‐S1S2s have increased integrin‐dependent motility in the presence of astrocytes via modulation of NRG and FGF receptor‐linked PI3K/AKT intracellular signaling and do not form boundaries with astrocytes in culture. SC‐astrocyte mixing is dependent on local NRG concentration and we propose that sulfatase enzymes influence the bioavailability of NRG ligand and thus influence SC behavior. We further demonstrate that injection of sulfatase expressing SCs into spinal cord white matter results in less glial reactivity than control SC injections comparable to that of OEC injections. Our data indicate that sulfatase‐mediated modification of the extracellular matrix can influence glial interactions with astrocytes, and that SCs engineered to express sulfatase may be more OEC‐like in character. This approach may be beneficial for cell transplant‐mediated spinal cord repair. GLIA 2016 GLIA 2017;65:19–3

Maternal immune activation and adolescent alcohol exposure increase alcohol drinking and disrupt cortical-striatal-hippocampal oscillations in adult offspring

Maternal immune activation (MIA) is strongly associated with an increased risk of developing mental illness in adulthood, which often co-occurs with alcohol misuse. The current study aimed to begin to determine whether MIA, combined with adolescent alcohol exposure (AE), could be used as a model with which we could study the neurobiological mechanisms behind such co-occurring disorders. Pregnant Sprague-Dawley rats were treated with polyI:C or saline on gestational day 15. Half of the offspring were given continuous access to alcohol during adolescence, leading to four experimental groups: controls, MIA, AE, and Dual (MIA + AE). We then evaluated whether MIA and/or AE alter: (1) alcohol consumption; (2) locomotor behavior; and (3) cortical-striatal-hippocampal local field potentials (LFPs) in adult offspring. Dual rats, particularly females, drank significantly more alcohol in adulthood compared to all other groups. MIA led to reduced locomotor behavior in males only. Using machine learning to build predictive models from LFPs, we were able to differentiate Dual rats from control rats and AE rats in both sexes, and Dual rats from MIA rats in females. These data suggest that Dual “hits” (MIA + AE) increases substance use behavior and disrupts activity in reward-related circuits, and that this may be a valuable heuristic model we can use to study the neurobiological underpinnings of co-occurring disorders. Our future work aims to extend these findings to other addictive substances to enhance the translational relevance of this model, as well as determine whether amelioration of these circuit disruptions can reduce substance use behavior

Modelling mammalian energetics: the heterothermy problem

Global climate change is expected to have strong effects on the world’s flora and fauna. As a result, there has been a recent increase in the number of meta-analyses and mechanistic models that attempt to predict potential responses of mammals to changing climates. Many models that seek to explain the effects of environmental temperatures on mammalian energetics and survival assume a constant body temperature. However, despite generally being regarded as strict homeotherms, mammals demonstrate a large degree of daily variability in body temperature, as well as the ability to reduce metabolic costs either by entering torpor, or by increasing body temperatures at high ambient temperatures. Often, changes in body temperature variability are unpredictable, and happen in response to immediate changes in resource abundance or temperature. In this review we provide an overview of variability and unpredictability found in body temperatures of extant mammals, identify potential blind spots in the current literature, and discuss options for incorporating variability into predictive mechanistic models

Disrupting the Repeat Domain of Premelanosome Protein (PMEL) Produces Dysamyloidosis and Dystrophic Ocular Pigment Reflective of Pigmentary Glaucoma

Pigmentary glaucoma has recently been associated with missense mutations in PMEL that are dominantly inherited and enriched in the protein’s fascinating repeat domain. PMEL pathobiology is intriguing because PMEL forms functional amyloid in healthy eyes, and this PMEL amyloid acts to scaffold melanin deposition. This is an informative contradistinction to prominent neurodegenerative diseases where amyloid formation is neurotoxic and mutations cause a toxic gain of function called “amyloidosis”. Preclinical animal models have failed to model this PMEL “dysamyloidosis” pathomechanism and instead cause recessively inherited ocular pigment defects via PMEL loss of function; they have not addressed the consequences of disrupting PMEL’s repetitive region. Here, we use CRISPR to engineer a small in-frame mutation in the zebrafish homolog of PMEL that is predicted to subtly disrupt the protein’s repetitive region. Homozygous mutant larvae displayed pigmentation phenotypes and altered eye morphogenesis similar to presumptive null larvae. Heterozygous mutants had disrupted eye morphogenesis and disrupted pigment deposition in their retinal melanosomes. The deficits in the pigment deposition of these young adult fish were not accompanied by any detectable glaucomatous changes in intraocular pressure or retinal morphology. Overall, the data provide important in vivo validation that subtle PMEL mutations can cause a dominantly inherited pigment pathology that aligns with the inheritance of pigmentary glaucoma patient pedigrees. These in vivo observations help to resolve controversy regarding the necessity of PMEL’s repeat domain in pigmentation. The data foster an ongoing interest in an antithetical dysamyloidosis mechanism that, akin to the amyloidosis of devastating dementias, manifests as a slow progressive neurodegenerative disease

Axon growth and guidance genes identify nascent, immature, and mature olfactory sensory neurons

Neurogenesis of projection neurons requires that axons be initiated, extended, and connected. Differences in the expression of axon growth and guidance genes must drive these events, but comprehensively characterizing these differences in a single neuronal type has not been accomplished. Guided by a catalog of gene expression in olfactory sensory neurons (OSNs), in situ hybridization and immunohistochemistry revealed that Cxcr4 and Dbn1 , two axon initiation genes, marked the developmental transition from basal progenitor cells to immature OSNs in the olfactory epithelium. The CXCR4 immunoreactivity of these nascent OSNs overlapped partially with markers of proliferation of basal progenitor cells and partially with immunoreactivity for GAP43, the canonical marker of immature OSNs. Intracellular guidance cue signaling transcripts Ablim1, Crmp1, Dypsl2, Dpysl3, Dpysl5, Gap43, Marcskl1, and Stmn1–4 were specific to, or much more abundant in, the immature OSN layer. Receptors that mediate axonal inhibition or repulsion tended to be expressed in both immature and mature OSNs ( Plxna1, Plxna4, Nrp2, Efna5 ) or specifically in mature OSNs ( Plxna3, Unc5b, Efna3, Epha5, Epha7 ), although some were specific to immature OSNs ( Plxnb1, Plxnb2, Plxdc2, Nrp1 ). Cell adhesion molecules were expressed either by both immature and mature OSNs ( Dscam, Ncam1, Ncam2, Nrxn1 ) or solely by immature OSNs ( Chl1, Nfasc1, Dscaml1 ). Given the loss of intracellular signaling protein expression, the continued expression of guidance cue receptors in mature OSNs is consistent with a change in the role of these receptors, perhaps to sending signals back to the cell body and nucleus. © 2010 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106698/1/22497_ftp.pd

Bioprocessing strategies to enhance the challenging isolation of neuro-regenerative cells from olfactory mucosa

Olfactory ensheathing cells (OECs) are a promising potential cell therapy to aid regeneration. However, there are significant challenges in isolating and characterizing them. In the current study, we have explored methods to enhance the recovery of cells expressing OEC marker p75NTR from rat mucosa. With the addition of a 24-hour differential adhesion step, the expression of p75NTR was significantly increased to 73 ± 5% and 46 ± 18% on PDL and laminin matrices respectively. Additionally, the introduction of neurotrophic factor NT-3 and the decrease in serum concentration to 2% FBS resulted in enrichment of OECs, with p75NTR at nearly 100% (100 ± 0% and 98 ± 2% on PDL and laminin respectively), and candidate fibroblast marker Thy1.1 decreased to zero. Culturing OECs at physiologically relevant oxygen tension (2–8%) had a negative impact on p75NTR expression and overall cell survival. Regarding cell potency, co-culture of OECs with NG108-15 neurons resulted in more neuronal growth and potential migration at atmospheric oxygen. Moreover, OECs behaved similarly to a Schwann cell line positive control. In conclusion, this work identified key bioprocessing fundamentals that will underpin future development of OEC-based cell therapies for potential use in spinal cord injury repair. However, there is still much work to do to create optimized isolation methods

The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision

Motile and non-motile cilia are associated with mutually-exclusive genetic disorders. Motile cilia propel sperm or extracellular fluids, and their dysfunction causes primary ciliary dyskinesia. Non-motile cilia serve as sensory/signalling antennae on most cell types, and their disruption causes single-organ ciliopathies such as retinopathies or multi-system syndromes. CFAP20 is a ciliopathy candidate known to modulate motile cilia in unicellular eukaryotes. We demonstrate that in zebrafish, cfap20 is required for motile cilia function, and in C. elegans, CFAP-20 maintains the structural integrity of non-motile cilia inner junctions, influencing sensory-dependent signalling and development. Human patients and zebrafish with CFAP20 mutations both exhibit retinal dystrophy. Hence, CFAP20 functions within a structural/functional hub centered on the inner junction that is shared between motile and non-motile cilia, and is distinct from other ciliopathy-associated domains or macromolecular complexes. Our findings suggest an uncharacterised pathomechanism for retinal dystrophy, and potentially for motile and non-motile ciliopathies in general

Identification of Anti-Malarial Compounds as Novel Antagonists to Chemokine Receptor CXCR4 in Pancreatic Cancer Cells

Despite recent advances in targeted therapies, patients with pancreatic adenocarcinoma continue to have poor survival highlighting the urgency to identify novel therapeutic targets. Our previous investigations have implicated chemokine receptor CXCR4 and its selective ligand CXCL12 in the pathogenesis and progression of pancreatic intraepithelial neoplasia and invasive pancreatic cancer; hence, CXCR4 is a promising target for suppression of pancreatic cancer growth. Here, we combined in silico structural modeling of CXCR4 to screen for candidate anti-CXCR4 compounds with in vitro cell line assays and identified NSC56612 from the National Cancer Institute's (NCI) Open Chemical Repository Collection as an inhibitor of activated CXCR4. Next, we identified that NSC56612 is structurally similar to the established anti-malarial drugs chloroquine and hydroxychloroquine. We evaluated these compounds in pancreatic cancer cells in vitro and observed specific antagonism of CXCR4-mediated signaling and cell proliferation. Recent in vivo therapeutic applications of chloroquine in pancreatic cancer mouse models have demonstrated decreased tumor growth and improved survival. Our results thus provide a molecular target and basis for further evaluation of chloroquine and hydroxychloroquine in pancreatic cancer. Historically safe in humans, chloroquine and hydroxychloroquine appear to be promising agents to safely and effectively target CXCR4 in patients with pancreatic cancer