Qualitative exploration of the views of healthy living champions from pharmacies in England.

BACKGROUND: In England, the 'Healthy Living Pharmacy (HLP)' initiative has been trialed; positive outcomes led to national roll-out across England to 20 pathfinder sites. A HLP provides health promotion/prevention services through a structured framework to meet local population need. Non-pharmacist staff receive additional training so that they can provide these services, and are known as Healthy Living Champions (HLCs). OBJECTIVES: To explore HLCs views on their role and to identify any barriers or facilitators in performing the role. METHODS: Fourteen semi-structured face-to-face interviews were conducted during February and March 2013 in NHS Dudley, and analysed using the principles of content analysis. RESULTS: Three themes emerged from the interviews; HLC job role; training; and public awareness. HLC staff showed high levels of motivation, a strong desire to help people and felt a sense of personal reward, resulting in increased levels of job satisfaction. Training had improved their confidence but they still had reservations in offering services such as alcohol intervention and weight management. All believed that public awareness was low despite advertising. CONCLUSION: HLCs were positive toward their new role and derived job satisfaction from helping people to improve their health, although on-going training and support was perceived as important

Democratizing HMO Regulation to Enforce the Rule of Rescue

Despite heightened public concern about HMOs, misguided regulatory measures have not guaranteed HMO patients access to the treatment options many consider vital. This Note recommends four changes to the current regulatory system that would preserve HMOs\u27 ability to control health care costs while allowing patients and doctors, rather than lawmakers or HMO administrators, to set health care priorities

Rfx6 Maintains the Functional Identity of Adult Pancreatic β Cells.

SummaryIncreasing evidence suggests that loss of β cell characteristics may cause insulin secretory deficiency in diabetes, but the underlying mechanisms remain unclear. Here, we show that Rfx6, whose mutation leads to neonatal diabetes in humans, is essential to maintain key features of functionally mature β cells in mice. Rfx6 loss in adult β cells leads to glucose intolerance, impaired β cell glucose sensing, and defective insulin secretion. This is associated with reduced expression of core components of the insulin secretion pathway, including glucokinase, the Abcc8/SUR1 subunit of KATP channels and voltage-gated Ca2+ channels, which are direct targets of Rfx6. Moreover, Rfx6 contributes to the silencing of the vast majority of “disallowed” genes, a group usually specifically repressed in adult β cells, and thus to the maintenance of β cell maturity. These findings raise the possibility that changes in Rfx6 expression or activity may contribute to β cell failure in humans

Cubic Augmentation of Planar Graphs

In this paper we study the problem of augmenting a planar graph such that it becomes 3-regular and remains planar. We show that it is NP-hard to decide whether such an augmentation exists. On the other hand, we give an efficient algorithm for the variant of the problem where the input graph has a fixed planar (topological) embedding that has to be preserved by the augmentation. We further generalize this algorithm to test efficiently whether a 3-regular planar augmentation exists that additionally makes the input graph connected or biconnected. If the input graph should become even triconnected, we show that the existence of a 3-regular planar augmentation is again NP-hard to decide.Comment: accepted at ISAAC 201

Replica-Immunogold Technique Applied to Studies on Measles Virus Morphogenesis

The replica technique was applied to studies on the dynamic process of measles virus budding on infected HeLa cells. Virus structures were identified by labeling with anti-measles antibodies and protein A-gold. The combination of these two methods enabled us (1) to characterize the sequence of virus budding at the plasma membrane, (2) to localize virus structures on cytoskeletons of infected cells, and (3) to study the influence of Ca2+ ions on virus structures at the plasma membrane. Studies on platinum carbon surface replicas suggest that the process of virus budding is similar to the genesis of cellular microvilli. Replicas prepared from cytoskeletons of infected cells reveal a close association of budding virus with actin filaments composing the outer parts of the networks. Replicas of apical plasma membranes isolated from infected cells show the attachment of viral nucleocapsids to the protoplasmic membrane face of infected cells. These nucleocapsids are not present on membranes prepared from cells treated with calcium and the ionophore A23187. In addition viral cell surface antigens become randomly distributed on these cells. The data suggest that measles virus morphogenesis at the plasma membrane of cultured cells is dependent on the function of the cytoskeleton and may be influenced by Ca2+ ions

Plasma Membrane Antigens Detected by Replica Techniques

Methods are introduced for in situ preparation of cell cultures grown on glass coverslips using the replica technique. Special equipment and handling procedures enabled us to prepare large-sized and stable replicas suitable for ultrastructural and immunocytochemical analysis of the different faces of the plasma membrane (PM): the extraplasmic surface (ES), the complementary extraplasmic (EF) and protoplasmic (PF) fracture face, and the protoplasmic surface (PS). Colloidal gold markers in combination with protein A and monospecific/monoclonal antibodies were used to identify virus-specific antigens at the ES of infected cells. Stereo replicas show a coincident location of gold-labeled virus antigens at the ES and structures visible at the EF as well as at the PS. In addition, the association of these antigens with cytoskeletal elements is demonstrated

Evaluation of Amino Acid Composition as a Geochronometer in Buried Soils on Mount Kenya, East Africa

A sequence of surface and buried paleosols from the slopes of Mount Kenya, East Africa, has been identified and dated by radiocarbon and amino acid dating techniques in order to elucidate the Quaternary history of the area. Buried paleosols vary in radiocarbon age from 900 to > 40,000 yrs BP. They have developed in glacial and periglacial deposits of variable texture, consisting of a high percentage of clasts of phonolite, basalt and syenite. All but two paleosols are located in the Afroalpine zone (above 3200 m). D/L ratios of amino acids in Ab horizons were determined in order to establish their reliability for relative age dating. Alanine, aspartic acid, glutamic acid, leucine, valine, and phenylalanine were routinely analyzed. Aspartic acid, as in other cases, proved reliable yielding remarkably consistent results, with higher ratios corresponding to increasing age. Other acids analyzed showed distinct trends, although not as convincing as aspartic acid. In most cases, the aspartic acid ratio/ age relationships were supported by radiocarbon dates. D/L ratios of aspartic acid varied from approximately 0.07 for modern samples, to approximately 0.45 in samples > 40,000 years old.On a identifié et daté, au radiocarbone et à l'aide de techniques de datations à l'acide aminé, des paléosols enfouis et de surface afin de comprendre l'évolution quaternaire de la région. Les datations au radiocarbone des paléosols enfouis varient de 900 à plus de 40 000 BP. Les sols se sont développés dans des dépôts glaciaires et périglaciaires de différentes textures, constitués de fragments de roches détritiques, de phonolite, de basalte et de syénite. Tous les paléosols, sauf deux, sont situés dans la zone afroalpine (au-dessus de 3200 m). On a déterminé par racémisation les rapports D/L des acides aminés dans les horizons Ab en vue d'évaluer leur fiabilité pour la datation des âges relatifs. On a fait l'analyse de l'alaline, de l'acide aspartique, de l'acide glutamique, de la leucine, de la valine et du phénylalaline. L'acide aspartique, comme dans d'autres cas, a donné des résultats particulièrement satisfaisants, les quotients plus élevés correspondant aux âges les plus anciens. D'autres acides montraient des tendances bien distinctes, mais moins convaincantes que dans le cas de l'acide aspartique. Ainsi, dans la plupart des cas, les relations quotients/âges de l'acide aspartique étaient corroborées par les datations au radiocarbone. Les rapports D/L de l'acide aspartique variaient d'environ 0,07 pour les échantillons modernes à environ 0,45 pour les échantillons de plus de 40 000 ans.Eine Série von an der Oberflâche Negenden und begrabenen Palàobôden von den Hàngen des Mount Kenya, Ost-Afrika, wurde mittels Radiokarbon- und Aminosâuredatierungs-techniken identifiziert und datiert, um die Geschichte dieses Gebiets im Quaternàr zu erhellen. Das durch Radiokarbon bestimmte Alter der begrabenen Palàobôden variiert von 900 bis > 40,000 Jahren v.u.Z. Dièse Bôden haben sich in glazialen und periglazialen Ablagerungen verschiedener Beschaffenheit entwickelt, welche zu einem hohen Prozentsatz aus Trùmmern von Phonolith, Basait und Syenit bestehen. AuBer zweien befinden sich aile Palàobôden in der afroalpinen Zone (oberhalb 3200 m). Die D/L Anteile der Aminosâuren in den Ab-Horizonten wurden bestimmt, um ihre Verlâpiichkeit bei der relativen Altersbestimmung festzustellen. Alamin, aspartische Sàure, Glutamin-Sàure, Leuzin, Valin und Phenylalanin wurden laufend analysiert. Wie in anderen Fallen erwies sich die aspartische Sàure als verlàpiich, indem sie bemerkenswert bestàndige Ergebnisse ergab, bei denen die hôheren Quotienten dem hôheren Alter entsprachen. Andere analysierte Sàuren zeigten ausgepràgte Trends, wenn auch nicht so ùberzeugend wie die aspartische Sàure. In den meisten Fallen wurden die Beziehungen Quotient/Alter der aspartischen Sàure durch Radiokarbondatierungen gestùtzt. Die D/L Anteile der aspartischen Sàure variierten von ungefâhr 0.07 fur moderne Proben bis ungefâhr 0.45 in Proben, die > 40,000 Jahre ait sind

An alternative polyadenylation signal in TCF7L2 generates isoforms that inhibit T cell factor/lymphoid-enhancer factor (TCF/LEF)-dependent target genes.

Journal ArticleResearch Support, Non-U.S. Gov't© The Author(s) 2011. This article is published with open access at Springerlink.comAIMS/HYPOTHESIS: Intronic single nucleotide polymorphisms within the transcription factor 7-like 2 (TCF7L2) gene are associated with risk of type 2 diabetes. It is widely hypothesised that the predisposing variation is involved in cis-regulation of TCF7L2 activity. The aim of this study was to seek evidence for the existence of novel TCF7L2 isoforms encoded within the type 2 diabetes-associated genomic region. METHODS: We searched expressed sequence tag (EST) databases for novel TCF7L2 transcripts and sought to validate the function and integrity of any isoforms found using a combination of RT-PCR, western blotting and reporter gene techniques. RESULTS: Analysis of EST databases suggested the presence of an alternative polyadenylation site located in intron 4 of TCF7L2. We used 3' rapid amplification of cDNA ends and real-time PCR to validate the integrity of this polyadenylation signal and show its wide use across human tissues. Western blotting results are consistent with the use of this polyadenylation signal to generate novel protein isoforms. The alternative polyadenylation signal results in the production of isoforms that retain the β-catenin binding domain but do not possess the high-mobility group box DNA-binding domain. Promoter-reporter gene assays suggest that these isoforms inhibit TCF7L2-dependent target genes by sequestering β-catenin. CONCLUSIONS/INTERPRETATION: We have identified a novel polyadenylation signal within TCF7L2 that can result in the production of isoforms that act to repress TCF/LEF-dependent target genes. These findings may provide new insights into the association of TCF7L2 with susceptibility to type 2 diabetes.Wellcome TrustMRCEuropean Community’s Seventh Framework Programm