Helen McNicol Sheldon

Helen McNicol Sheldon, Class of 1940, majored in Sociology. This was recorded at Sheldon\u27s home

The role of the dementia specialist nurse in acute care: a scoping review

Aims and objectivesTo identify the potential benefits of dementia specialist nursing and to inform the implementation of roles to support people with dementia during hospital admission.BackgroundExtended stays and adverse events mean that hospital admissions are costly for people with dementia, and patient experiences and outcomes can be poor. Specialist nurses have been identified as having potential to enhance care quality, reduce excess stays and reduce costs, but the evidence base for dementia specialist nurse roles has not previously been synthesised.DesignScoping review.Data sourcesCochrane Library, Campbell Collaboration, Clinical Evidence, Evidence-Based Medicine, York Centre for Reviews and Dissemination, PubMed, Medline, CINAHL and PsycInfo databases and internet searches and personal libraries/expert consultation to identify grey literature.MethodsInitial scoping searches were used to inform more focused systematic searches. Studies directly evaluating dementia nurse specialist roles or giving evidence of effectiveness of interventions/services that could be delivered by them to improve core outcomes were identified by one reviewer and verified by a second reviewer.ResultsWhile direct evidence for the effectiveness of these roles is lacking, a number of areas were identified in which a nurse specialist role could make a contribution, including preventing adverse events and improving patient experiences and outcomes. There is a considerable body of evidence for the effectiveness of these interventions although the volume of evidence for specific interventions is not always significant.ConclusionsThe evidence indicates that a skilled dementia specialist nurse, undertaking a clearly defined role, and working directly with people with dementia and their carers for a significant proportion of the time, could benefit people with dementia in hospitals and their family carers.Relevance to clinical practiceClear guidance for the development and implementation of dementia specialist nurse roles in acute hospital settings.<br/

Haemophilus influenzae type b reemergence after combination immunization

An increase in Haemophilus influenzae type b (Hib) in British children has been linked to the widespread use of a diphtheria/tetanus/acellular pertussis combination vaccine (DTaP-Hib). We measured anti-polyribosyl-ribitol phos- phate antibody concentration and avidity before and after a Hib booster in 176 children 2–4 years of age who had received 3 doses of DTP-Hib (either DT whole cell pertus- sis-Hib or DTaP-Hib) combination vaccine in infancy. We also measured pharyngeal carriage of Hib. Antibody con- centrations before and avidity indices after vaccination were low (geometric mean concentration 0.46μg/mL, 95% confidence interval [CI] 0.36–0.58; geometric mean avidity index 0.16, 95% CI 0.14–0.18) and inversely related to the number of previous doses of DTaP-Hib (p = 0.02 and p<0.001, respectively). Hib was found in 2.1% (95% CI 0.7%–6.0%) of study participants. Our data support an association between DTaP-Hib vaccine combinations and clinical Hib disease through an effect on antibody concen- tration and avidit

The Cross-Species Mycobacterial Growth Inhibition Assay (MGIA) Project, 2010-2014.

The development of a functional biomarker assay in the tuberculosis (TB) field would be widely recognized as a major advance in efforts to develop and to test novel TB vaccine candidates efficiently. We present preliminary studies using mycobacterial growth inhibition assays (MGIAs) to detect Mycobacterium bovis BCG vaccine responses across species, and we extend this work to determine whether a standardized MGIA can be applied in characterizing new TB vaccines. The comparative MGIA studies reviewed here aimed to evaluate robustness, reproducibility, and ability to reflect in vivo responses. In doing so, they have laid the foundation for the development of a MGIA that can be standardized and potentially qualified. A major challenge ahead lies in better understanding the relationships between in vivo protection, in vitro growth inhibition, and the immune mechanisms involved. The final outcome would be a MGIA that could be used with confidence in TB vaccine trials. We summarize data arising from this project, present a strategy to meet the goals of developing a functional assay for TB vaccine testing, and describe some of the challenges encountered in performing and transferring such assays

DLL4-Notch signaling mediates tumor resistance to anti-VEGF therapy in vivo.

Resistance to VEGF inhibitors is emerging as a major clinical problem. Notch signaling has been implicated in tumor angiogenesis. Therefore, to investigate mechanisms of resistance to angiogenesis inhibitors, we transduced human glioblastoma cells with retroviruses encoding Notch delta-like ligand 4 (DLL4), grew them as tumor xenografts and then treated the murine hosts with the VEGF-A inhibitor bevacizumab. We found that DLL4-mediated tumor resistance to bevacizumab in vivo. The large vessels induced by DLL4-Notch signaling increased tumor blood supply and were insensitive to bevacizumab. However, blockade of Notch signaling by dibenzazepine, a γ-secretase inhibitor, disrupted the large vessels and abolished the tumor resistance. Multiple molecular mechanisms of resistance were shown, including decreased levels of hypoxia-induced VEGF and increased levels of the VEGF receptor VEGFR1 in the tumor stroma, decreased levels of VEGFR2 in large blood vessels, and reduced levels of VEGFR3 overall. DLL4-expressing tumors were also resistant to a VEGFR targeting multikinase inhibitor. We also observed activation of other pathways of tumor resistance driven by DLL4-Notch signaling, including the FGF2-FGFR and EphB4-EprinB2 pathways, the inhibition of which reversed tumor resistance partially. Taken together, our findings show the importance of classifying mechanisms involved in angiogenesis in tumors, and how combination therapy to block DLL4-Notch signaling may enhance the efficacy of VEGF inhibitors, particularly in DLL4-upregulated tumors, and thus provide a rational base for the development of novel strategies to overcome antiangiogenic resistance in the clinic

The Iowa Homemaker vol.3, no.3-4

Table of Contents The Architectural Design of a Home by Allen Holmes Kimball, page 1 “For a Man’s House Is His Castle” by Alda Wilson, page 2 The Economics of Consumption compiled by John E. Brindley, page 3 Sunfast and Tubfast Materials by Pearl Apland, page 5 On Our Street by Juanita J. Beard, page 6 Who Is Responsible for the Child? by Orange H. Cessna, page 7 Summer Suppers by N. Beth Bailey, page 8 Vacation First Aid by Dr. Mary Sheldon, page 9 Episodes Concerning Evolution of Home Economics by Ruth Elaine Wilson, page 10 Extravagant Economics by Blanche Ingersoll, page 11 Breakfast Bridge by Eleanor Murray, page 12 Veishea Celebrates First Birthday by Helen G. Lamb, page 1

Single cell tracking of gadolinium labeled CD4(+) T cells by laser ablation inductively coupled plasma mass spectrometry

Cellular therapy is emerging as a promising alternative to conventional immunosuppression in the fields of haematopoietic stem cell (HSC) transplantation, autoimmune disease and solid organ transplantation. Determining the persistence of cell-based therapies in vivo is crucial to understanding their regulatory function and requires the combination of an extremely sensitive detection technique and a stable, long-lifetime cell labelling agent. This paper reports the first application of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to perform single cell detection of T cell populations relevant to cellular immunotherapy. Purified human CD4+ T cells were labelled with commercially available Gd-based MRI contrast agents, Omniscan® and Dotarem®, which enabled passive loading of up to 108 Gd atoms per cell. In mixed preparations of labelled and unlabelled cells, LA-ICP-MS was capable of enumerating labelled cells at close to the predicted ratio. More importantly, LA-ICP-MS single cell analysis demonstrated that the cells retained sufficient label to remain detectable for up to 10 days post-labelling both in vitro and in vivo in an immunodeficient mouse model

Elevated expression of the adhesion GPCR ADGRL4/ELTD1 promotes endothelial sprouting angiogenesis without activating canonical GPCR signalling.

Funder: Rhodes Scholarships; doi: http://dx.doi.org/10.13039/501100000697Funder: Clarendon ScholarshipFunder: Ernest Oppenheimer Memorial Trust; doi: http://dx.doi.org/10.13039/501100009978Funder: European Union (European Social Fund)Funder: Free State of SaxonyFunder: Cancer Research UK; doi: http://dx.doi.org/10.13039/501100000289Funder: Breast Cancer Research Foundation; doi: http://dx.doi.org/10.13039/100001006ADGRL4/ELTD1 is an orphan adhesion GPCR (aGPCR) expressed in endothelial cells that regulates tumour angiogenesis. The majority of aGPCRs are orphan receptors. The Stachel Hypothesis proposes a mechanism for aGPCR activation, in which aGPCRs contain a tethered agonist (termed Stachel) C-terminal to the GPCR-proteolytic site (GPS) cleavage point which, when exposed, initiates canonical GPCR signalling. This has been shown in a growing number of aGPCRs. We tested this hypothesis on ADGRL4/ELTD1 by designing full length (FL) and C-terminal fragment (CTF) ADGRL4/ELTD1 constructs, and a range of potential Stachel peptides. Constructs were transfected into HEK293T cells and HTRF FRET, luciferase-reporter and Alphascreen GPCR signalling assays were performed. A stable ADGRL4/ELTD1 overexpressing HUVEC line was additionally generated and angiogenesis assays, signalling assays and transcriptional profiling were performed. ADGRL4/ELTD1 has the lowest GC content in the aGPCR family and codon optimisation significantly increased its expression. FL and CTF ADGRL4/ELTD1 constructs, as well as Stachel peptides, did not activate canonical GPCR signalling. Furthermore, stable overexpression of ADGRL4/ELTD1 in HUVECs induced sprouting angiogenesis, lowered in vitro anastomoses, and decreased proliferation, without activating canonical GPCR signalling or MAPK/ERK, PI3K/AKT, JNK, JAK/HIF-1α, beta catenin or STAT3 pathways. Overexpression upregulated ANTXR1, SLC39A6, HBB, CHRNA, ELMOD1, JAG1 and downregulated DLL4, KIT, CCL15, CYP26B1. ADGRL4/ELTD1 specifically regulates the endothelial tip-cell phenotype through yet undefined signalling pathways

The ELT-2 GATA-factor and the global regulation of transcription in the C. elegans intestine

AbstractA SAGE library was prepared from hand-dissected intestines from adult Caenorhabditis elegans, allowing the identification of >4000 intestinally-expressed genes; this gene inventory provides fundamental information for understanding intestine function, structure and development. Intestinally-expressed genes fall into two broad classes: widely-expressed “housekeeping” genes and genes that are either intestine-specific or significantly intestine-enriched. Within this latter class of genes, we identified a subset of highly-expressed highly-validated genes that are expressed either exclusively or primarily in the intestine. Over half of the encoded proteins are candidates for secretion into the intestinal lumen to hydrolyze the bacterial food (e.g. lysozymes, amoebapores, lipases and especially proteases). The promoters of this subset of intestine-specific/intestine-enriched genes were analyzed computationally, using both a word-counting method (RSAT oligo-analysis) and a method based on Gibbs sampling (MotifSampler). Both methods returned the same over-represented site, namely an extended GATA-related sequence of the general form AHTGATAARR, which agrees with experimentally determined cis-acting control sequences found in intestine genes over the past 20 years. All promoters in the subset contain such a site, compared to <5% for control promoters; moreover, our analysis suggests that the majority (perhaps all) of genes expressed exclusively or primarily in the worm intestine are likely to contain such a site in their promoters. There are three zinc-finger GATA-type factors that are candidates to bind this extended GATA site in the differentiating C. elegans intestine: ELT-2, ELT-4 and ELT-7. All evidence points to ELT-2 being the most important of the three. We show that worms in which both the elt-4 and the elt-7 genes have been deleted from the genome are essentially wildtype, demonstrating that ELT-2 provides all essential GATA-factor functions in the intestine. The SAGE analysis also identifies more than a hundred other transcription factors in the adult intestine but few show an RNAi-induced loss-of-function phenotype and none (other than ELT-2) show a phenotype primarily in the intestine. We thus propose a simple model in which the ELT-2 GATA factor directly participates in the transcription of all intestine-specific/intestine-enriched genes, from the early embryo through to the dying adult. Other intestinal transcription factors would thus modulate the action of ELT-2, depending on the worm's nutritional and physiological needs

Ex vivo mycobacterial growth inhibition assay (MGIA) for tuberculosis vaccine testing - a protocol for mouse splenocytes

The testing of vaccines for tuberculosis is costly and time-consuming, and dependent on preclinical animal challenge models and clinical trials. We have recently developed a mycobacterial growth inhibition assay (MGIA) to test vaccine efficacy ex vivo. This assay measures the summative effect of the host immune response and may serve as a novel tool to facilitate vaccine testing. It has generated much interest recently, and to facilitate technology transfer and reproducibility between laboratories, we here describe a detailed protocol for an ex vivo MGIA in mouse splenocytes.</jats:p