409 research outputs found

    The mediating effect of perceived organizational support on espoused safety attitudes: a field study

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    This research examined a proposed mediated model of safety attitudes and perceived organizational support in affecting safety outcomes in a population of nurses within a West Texas community hospital. Participants completed questionnaires pertaining to the aforementioned measures, and supervisors were solicited to complete a questionnaire pertaining to safety behaviors of subordinates within their respective departments. Data analysis revealed significant correlations among safety attitudes and perceived organizational support but failed to show support for a mediated model. Explanations as to why hypotheses were not supported are discussed, as well as avenues for future research

    Water Quality, nutrients and the European Union’s Water Framework Directive in a lowland agricultural region: Suffolk, south-east England.

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    The water quality of 13 rivers in the lowland, agricultural county of Suffolk is investigated using routine monitoring data for the period 1981 to 2006 collected by the Environment Agency of England and Wales (EA), and its predecessors, with particular emphasis on phosphorus (as total reactive phosphorus, TRP) and total (dissolved and particulate) oxidised nitrogen (TOxN – predominantly nitrate NO3). Major ion and flow data are used to outline fundamental hydrochemical characteristics related to the groundwater provenance of base-flow waters. Relative load contributions from point and diffuse sources are approximated using Load Apportionment Modelling for both TRP and TOxN where concurrent flow and concentration data are available. Analyses indicate a mixture of point and diffuse sources of TRP, with the former being dominant during low flow periods, while for TOxN diffuse sources dominate. Out of 59 sites considered, 53 (90%) were found to have annual average TRP concentrations greater than 0.05 mg P l-1, and 36 (61%) had average concentrations over 0.120 mg P l-1, the upper thresholds for ‘High’ and ‘Good’ ecological status, respectively. Correspondingly, for TOxN, most of the rivers are already within 70% of the 11.3 mg N l-1 threshold, with two rivers (Wang and Ore) being consistently greater than this. It is suggested that the major challenge is to characterise and control point-source TRP inputs which, being predominant during the late spring and summer low-flow period, coincide with the peak of primary biological production, thus presenting the major challenge to achieving ‘good’ ecological status under the Water Framework Directive. Results show that considerable effort is still required to ensure appropriate management and develop tools for decision-support

    Detección de efecto adverso a benzodiacepinas de vida media larga en paciente anciano, optimización de la farmacoterapia desde la farmacia comunitaria.

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    Pciente de 96 años que desde hace una semana sufre un desequilibrio en su estado de salud que alerta a sus familiares, sufre un cuadro de letárgia, pérdida del equilibrio y una caida la noche anterior al intentar ir al aseo. Se decide derivan a la apciente al servicio de seguimiento farmacoterapéutico de la oficina de fármacia. La paciente presenta un cuadro de hipotensión, pérdida del equilibrio, mareos y caidas posiblemente causados por el fármaco antihipertensivo que toma. Se recomienda valorar la necesidad de la benzodiacepina que toma la paciente y pensar en cambiarla por otra benzodiacepina de acción corta, como zolpidem o zoplicona, para evitar la sedación excesiva durante el día. El médico acepta nuestras sugerencias. Se le reduce la dosis del fármaco antihipertensivo y se le cambia a una benzodiacepina de acción corta. La paciente ya no sufre mareos, pérdidas del equilibrio ni caidas y las cifras de presión arterial están en rangos adecuados

    Detección de efecto adverso a benzodiacepinas de vida media larga en paciente anciano, optimización de la farmacoterapia desde la farmacia comunitaria.

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    Pciente de 96 años que desde hace una semana sufre un desequilibrio en su estado de salud que alerta a sus familiares, sufre un cuadro de letárgia, pérdida del equilibrio y una caida la noche anterior al intentar ir al aseo. Se decide derivan a la apciente al servicio de seguimiento farmacoterapéutico de la oficina de fármacia. La paciente presenta un cuadro de hipotensión, pérdida del equilibrio, mareos y caidas posiblemente causados por el fármaco antihipertensivo que toma. Se recomienda valorar la necesidad de la benzodiacepina que toma la paciente y pensar en cambiarla por otra benzodiacepina de acción corta, como zolpidem o zoplicona, para evitar la sedación excesiva durante el día. El médico acepta nuestras sugerencias. Se le reduce la dosis del fármaco antihipertensivo y se le cambia a una benzodiacepina de acción corta. La paciente ya no sufre mareos, pérdidas del equilibrio ni caidas y las cifras de presión arterial están en rangos adecuados

    The Epithelial Sodium Channel (ENaC) Establishes a Trafficking Vesicle Pool Responsible for Its Regulation

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    The epithelial sodium channel (ENaC) is the rate-limiting step for sodium reabsorption across tight epithelia. Cyclic-AMP (cAMP) stimulation promotes ENaC trafficking to the apical surface to increase channel number and transcellular Na+ transport. Removal of corticosteroid supplementation in a cultured cortical collecting duct cell line reduced ENaC expression. Concurrently, the number of vesicles trafficked in response to cAMP stimulation, as measured by a change in membrane capacitance, also decreased. Stimulation with aldosterone restored both the basal and cAMP-stimulated ENaC activity and increased the number of exocytosed vesicles. Knocking down ENaC directly decreased both the cAMP-stimulated short-circuit current and capacitance response in the presence of aldosterone. However, constitutive apical recycling of the Immunoglobulin A receptor was unaffected by alterations in ENaC expression or trafficking. Fischer Rat Thyroid cells, transfected with α,β,γ-mENaC had a significantly greater membrane capacitance response to cAMP stimulation compared to non-ENaC controls. Finally, immunofluorescent labeling and quantitation revealed a smaller number of vesicles in cells where ENaC expression was reduced. These findings indicate that ENaC is not a passive passenger in regulated epithelial vesicle trafficking, but plays a role in establishing and maintaining the pool of vesicles that respond to cAMP stimulation. © 2012 Edinger et al

    PIP5KIβ Selectively Modulates Apical Endocytosis in Polarized Renal Epithelial Cells

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    Localized synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] at clathrin coated pits (CCPs) is crucial for the recruitment of adaptors and other components of the internalization machinery, as well as for regulating actin dynamics during endocytosis. PtdIns(4,5)P2 is synthesized from phosphatidylinositol 4-phosphate by any of three phosphatidylinositol 5-kinase type I (PIP5KI) isoforms (α, β or γ). PIP5KIβ localizes almost exclusively to the apical surface in polarized mouse cortical collecting duct cells, whereas the other isoforms have a less polarized membrane distribution. We therefore investigated the role of PIP5KI isoforms in endocytosis at the apical and basolateral domains. Endocytosis at the apical surface is known to occur more slowly than at the basolateral surface. Apical endocytosis was selectively stimulated by overexpression of PIP5KIβ whereas the other isoforms had no effect on either apical or basolateral internalization. We found no difference in the affinity for PtdIns(4,5)P2-containing liposomes of the PtdIns(4,5)P2 binding domains of epsin and Dab2, consistent with a generic effect of elevated PtdIns(4,5)P2 on apical endocytosis. Additionally, using apical total internal reflection fluorescence imaging and electron microscopy we found that cells overexpressing PIP5KIβ have fewer apical CCPs but more internalized coated structures than control cells, consistent with enhanced maturation of apical CCPs. Together, our results suggest that synthesis of PtdIns(4,5)P2 mediated by PIP5KIβ is rate limiting for apical but not basolateral endocytosis in polarized kidney cells. PtdIns(4,5)P2 may be required to overcome specific structural constraints that limit the efficiency of apical endocytosis. © 2013 Szalinski et al

    Human Nail Plate Modifications Induced by Onychomycosis : Implications for Topical Therapy

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    Open Access - This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are creditedConclusions: Onchomycotic nails presented a thicker but more porous barrier, and its eroded intracellular matrix rendered the tissue more permeable to topically applied chemicals when an aqueous vehicle was used.Purpose: Through the characterisation of the human onchomycotic nail plate this study aimed to inform the design of new topical ungual formulations.Methods: The mechanical properties of the human nail were characterised using a Lloyd tensile strength tester. The nail’s density was determined via pycnometry and the nail’s ultrastructure by electron microscopy. Raman spectroscopy analysed the keratin disulphide bonds within the nail and its permeability properties were assessed by quantifying water and rhodamine uptake.Results: Chronic in vivo nail plate infection increased human nailplate thickness (healthy 0.49 ± 0.15 mm; diseased 1.20 ± 0.67 mm), but reduced its tensile strength (healthy 63.7 ± 13.4 MPa; diseased 41.7 ± 5.0 MPa) and density (healthy 1.34 ± 0.01 g/cm3; diseased 1.29 ± 0.00 g/cm3). Onchomycosis caused cell-cell separation, without disrupting the nail disulfide bonds or desmosomes. The diseased and healthy nails showed equivalent water uptake profiles, but the rhodamine penetration was 4-fold higher in the diseased nails using a PBS vehicle and 3 -fold higher in an ethanol/PBS vehicle.Peer reviewe

    The effectiveness of problem solving therapy in deprived South African communities: results from a pilot study

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    <p>Abstract</p> <p>Background</p> <p>The majority of South Africans with a DSM-IV diagnosis receive no treatment for their mental health problems. There is a move to simplify treatment for common mental disorders (CMDs) in order to ease access. Brief problem solving therapy (PST) might fill the treatment gap for CMD's in deprived communities in South Africa. This pilot study evaluates the feasibility, acceptability and effectiveness of this PST program for CMD's in deprived communities around Cape Town.</p> <p>Methods</p> <p>A Dutch problem solving program was adapted and translated into English, Xhosa and Afrikaans and thereafter implemented in townships around Cape Town. An initial attempt to recruit participants for online PST proved difficult, and so the program was adapted to a booklet format. Volunteers experiencing psychological distress were invited to participate in the either individually or group delivered 5-week during self-help program. To evaluate the effectiveness, psychological distress was administered through self-report questionnaires. After completion of the intervention participants also rated the program on various acceptability aspects.</p> <p>Results</p> <p>Of 103 participants, 73 completed 5 weeks of brief PST in a booklet/workshop format. There were significantly more dropouts in those who used the booklet individually than in the group. Psychological distress measured on the K-10 and SRQ fell significantly and the program was evaluated positively.</p> <p>Conclusions</p> <p>The results suggest that brief problem solving in a booklet/workshop format may be an effective, feasible and acceptable short-term treatment for people with CMD's in deprived communities. In this setting, group delivery of PST had lower drop-out rates than individual delivery, and was more feasible and acceptable. Randomized controlled trials are needed to evaluate the effect of brief self-help PST more rigorously.</p

    Enhancement of Polymeric Immunoglobulin Receptor Transcytosis by Biparatopic VHH

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    The polymeric immunoglobulin receptor (pIgR) ensures the transport of dimeric immunoglobulin A (dIgA) and pentameric immunoglobulin M (pIgM) across epithelia to the mucosal layer of for example the intestines and the lungs via transcytosis. Per day the human pIgR mediates the excretion of 2 to 5 grams of dIgA into the mucosa of luminal organs. This system could prove useful for therapies aiming at excretion of compounds into the mucosa. Here we investigated the use of the variable domain of camelid derived heavy chain only antibodies, also known as VHHs or Nanobodies®, targeting the human pIgR, as a transport system across epithelial cells. We show that VHHs directed against the human pIgR are able to bind the receptor with high affinity (∼1 nM) and that they compete with the natural ligand, dIgA. In a transcytosis assay both native and phage-bound VHH were only able to get across polarized MDCK cells that express the human pIgR gene in a basolateral to apical fashion. Indicating that the VHHs are able to translocate across epithelia and to take along large particles of cargo. Furthermore, by making multivalent VHHs we were able to enhance the transport of the compounds both in a MDCK-hpIgR and Caco-2 cell system, probably by inducing receptor clustering. These results show that VHHs can be used as a carrier system to exploit the human pIgR transcytotic system and that multivalent compounds are able to significantly enhance the transport across epithelial monolayers
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