Attaching NorA efflux pump inhibitors to methylene blue enhances antimicrobial photodynamic inactivation of Escherichia coli and Acinetobacter baumannii in vitro and in vivo

Resistance of bacteria to antibiotics is a public health concern worldwide due to the increasing failure of standard antibiotic therapies. Antimicrobial photodynamic inactivation (aPDI) is a promising non-antibiotic alternative for treating localized bacterial infections that uses non-toxic photosensitizers and harmless visible light to produce reactive oxygen species and kill microbes. Phenothiazinium photosensitizers like methylene blue (MB) and toluidine blue O are hydrophobic cations that are naturally expelled from bacterial cells by multidrug efflux pumps, which reduces their effectiveness. We recently reported the discovery of a NorA efflux pump inhibitor-methylene blue (EPI-MB) hybrid compound INF55-(Ac)en-MB that shows enhanced photodynamic inactivation of the Gram-positive bacterium methicillin-resistant Staphylococcus aureus (MRSA) relative to MB, both in vitro and in vivo. Here, we report the surprising observation that INF55-(Ac)en-MB and two related hybrids bearing the NorA efflux pump inhibitors INF55 and INF271 also show enhanced aPDI activity in vitro (relative to MB) against the Gram-negative bacteria Escherichia coli and Acinetobacter baumannii, despite neither species expressing the NorA pump. Two of the hybrids showed superior effects to MB in murine aPDI infection models. The findings motivate wider exploration of aPDI with EPI-MB hybrids against Gram-negative pathogens and more detailed studies into the molecular mechanisms underpinning their activity

Activity interventions to improve the experience of care in hospital for people living with dementia: a systematic review

Background: An increasingly high number of patients admitted to hospital have dementia. Hospital environments can be particularly confusing and challenging for people living with dementia (Plwd) impacting their wellbeing and the ability to optimize their care. Improving the experience of care in hospital has been recognized as a priority, and non-pharmacological interventions including activity interventions have been associated with improved wellbeing and behavioral outcomes for Plwd in other settings. This systematic review aimed at evaluating the effectiveness of activity interventions to improve experience of care for Plwd in hospital. Methods: Systematic searches were conducted in 16 electronic databases up to October 2019. Reference lists of included studies and forward citation searching were also conducted. Quantitative studies reporting comparative data for activity interventions delivered to Plwd aiming to improve their experience of care in hospital were included. Screening for inclusion, data extraction and quality appraisal were performed independently by two reviewers with discrepancies resolved by discussion with a third where necessary. Standardized mean differences (SMDs) were calculated where possible to support narrative statements and aid interpretation. Results: Six studies met the inclusion criteria (one randomized and five non-randomized uncontrolled studies) including 216 Plwd. Activity interventions evaluated music, art, social, psychotherapeutic, and combinations of tailored activities in relation to wellbeing outcomes. Although studies were generally underpowered, findings indicated beneficial effects of activity interventions with improved mood and engagement of Plwd while in hospital, and reduced levels of responsive behaviors. Calculated SMDs ranged from very small to large but were mostly statistically non-significant. Conclusions: The small number of identified studies indicate that activity-based interventions implemented in hospitals may be effective in improving aspects of the care experience for Plwd. Larger well-conducted studies are needed to fully evaluate the potential of this type of non-pharmacological intervention to improve experience of care in hospital settings, and whether any benefits extend to staff wellbeing and the wider ward environment.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.Funding was provided by the Health Services and Delivery Research programme of the National Institute for Health Research, and the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South West Peninsula, now recommissioned as NIHR Applied Research Collaboration (ARC) South West Peninsula. The funding body had no role in design of the study, analysis and interpretation of the data or writing of the manuscript.published version, accepted version, submitted versio

An Alternative Method to Obtain the Quark Polarization of the Nucleon

An alternate method is described to extract the quark contribution to the spin of the nucleon directly from the first moment of the deuteron structure function, $g^d_1$. It is obtained without recourse to the use of input on the nucleon wave function from hyperon decays involving the flavor symmetry parameters, F and D. The result for the quark polarization of the nucleon, $\Delta\Sigma_ N,$ is in good agreement with the values of the singlet axial current matrix element, $a_0$, obtained from recent next-to-leading order analyses of current proton, neutron and deuteron data.Comment: 7 pages, 1 figur

The experiences of hospital staff who provide care for people living with dementia: A systematic review and synthesis of qualitative studies

Aims and objectives: To systematically review and synthesise qualitative data from studies exploring the experiences of hospital staff who care for people living with dementia (Plwd). Background: In hospital, the number of Plwd continues to rise; however, their experiences of care remain problematic. Negative experiences of care are likely to contribute to poorer mental and physical health outcomes for Plwd while in hospital and after discharge. Experiences of the hospital staff who care for Plwd can also be poor or unrewarding. It is important to understand the experiences of staff in order to improve staff well-being and ultimately the experience of care for Plwd while in hospital. Design: Systematic review and evidence synthesis of qualitative research. Data sources: We searched 16 electronic databases in March 2018 and completed forward and backward citation chasing. Methods: Eligible studies explored the experiences of paid and unpaid staff providing care in hospital for Plwd. Study selection was undertaken independently by two reviewers, and quality appraisal was conducted. We prioritised included studies according to richness of text, methodological rigour and conceptual contribution. We adopted approaches of meta-ethnography to analyse study findings, creating a conceptual model to represent the line of argument. Findings: Forty-five studies reported in 58 papers met the inclusion criteria, and of these, we prioritised 19 studies reported in 24 papers. The line of argument was that Institutions can improve staff experiences of care for Plwd by fostering person-centred care (PCC). PCC aligned with staff perceptions of 'good care'; however, staff often felt prevented from providing PCC because of care cultures that prioritised tasks, routines and physical health. Staff experienced conflict over the care they wanted to give versus the care they were able to give, and this caused moral distress. When staff were able to provide PCC, this increased experiences of job satisfaction and emotional well-being. Conclusions: Person-centred care not only has the potential to improve the experience of care for Plwd and their carers, but can also improve the experiences of hospital staff caring for Plwd. However, without institutional-level changes, hospital staff are often unable to provide PCC even when they have the experience and knowledge to do so. Implications for practice: Institutional-level areas for change include the following: training; performance indicators and ward cultures that prioritise psychological needs alongside physical needs; adequate staffing levels; inclusive approaches to carers; physical environments that promote familiarisation, social interaction and occupation; systems of documentation about individual needs of Plwd; and cultures of sharing knowledge across hierarchies.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.HS&DR 14/19/16/Health Services and Delivery Research Programmepublished version, accepted version (12 month embargo), submitted versio

High Energy Hadron-Nucleus Cross Sections and Their Extrapolation to Cosmic Ray Energies

Old models of the scattering of composite systems based on the Glauber model of multiple diffraction are applied to hadron-nucleus scattering. We obtain an excellent fit with only two free parameters to the highest energy hadron-nucleus data available. Because of the quality of the fit and the simplicity of the model it is argued that it should continue to be reliable up to the highest cosmic ray energies. Logarithmic extrapolations of proton-proton and proton-antiproton data are used to calculate the proton-air cross sections at very high energy. Finally, it is observed that if the exponential behavior of the proton-antiproton diffraction peak continues into the few TeV energy range it will violate partial wave unitarity. We propose a simple modification that will guarantee unitarity throughout the cosmic ray energy region.Comment: 8 pages, 9 postscript figures. This manuscript replaces a partial manuscript incorrectly submitte

Valence Quark Spin Distribution Functions

The hyperfine interactions of the constituent quark model provide a natural explanation for many nucleon properties, including the Delta-N splitting, the charge radius of the neutron, and the observation that the proton's quark distribution function ratio d(x)/u(x)->0 as x->1. The hyperfine-perturbed quark model also makes predictions for the nucleon spin-dependent distribution functions. Precision measurements of the resulting asymmetries A_1^p(x) and A_1^n(x) in the valence region can test this model and thereby the hypothesis that the valence quark spin distributions are "normal".Comment: 16 pages, 2 Postscript figure

Reversal of graft-versus-host disease with infusion of autologous bone marrow

Graft-versus-host disease (GVHD) remains a major complication of bone marrow transplantation. This report describes reversal of GVHD by infusion of stored recipient bone marrow following combined liver-bone marrow allotransplantation. Graft-versus-host disease developed at the end of the first postoperative week. The skin involvement progressively spread to approximately 80% of the body surface and was not affected by modification of the immunosuppressive treatment. On the 42nd and 43rd postoperative day 1.23 × 108 and 1.6 × 108 autologous bone marrow cells per kg of recipient body weight were infused. The skin rush began to dramatically improve and resolved within 2 wk from the autologous marrow infusion. Autologous bone marrow storage previous to allogeneic bone marrow transplantation for tolerance induction could constitute a safety net in case of occurrence of GVHD. © 1994

Next-to-Leading Order Analysis of Inclusive and Semi-inclusive Polarized Data

We present a combined next-to-leading order QCD analysis to data on both inclusive and semi-inclusive polarized deep inelastic scattering asymmetries. Performing NLO QCD global fits with different sets of observables, we evaluate the impact of the very recent semi-inclusive results presented by SMC in the extraction of NLO polarized parton distributions.Comment: 22 pages, 4 figures include

Chiral Symmetry Breaking in Quenched Massive Strong-Coupling QED4_4

We present results from a study of subtractive renormalization of the fermion propagator Dyson-Schwinger equation (DSE) in massive strong-coupling quenched QED$_4$. Results are compared for three different fermion-photon proper vertex {\it Ans\"{a}tze\/}: bare $\gamma^\mu$, minimal Ball-Chiu, and Curtis-Pennington. The procedure is straightforward to implement and numerically stable. This is the first study in which this technique is used and it should prove useful in future DSE studies, whenever renormalization is required in numerical work.Comment: REVTEX 3.0, 15 pages plus 7 uuencoded PostScript figure

Spin-Dependent Twist-Four Matrix Elements from g_1 Data in the Resonance Region

Matrix elements of spin-dependent twist-four operators are extracted from recent data on the spin-dependent g_1 structure function of the proton and deuteron in the resonance region. We emphasize the need to include the elastic contributions to the first moments of the structure functions at Q^2 < 2 GeV^2. The coefficients of the 1/Q^2 corrections to the Ellis-Jaffe sum rules are found to be 0.04 \pm 0.02 and 0.03 \pm 0.04 GeV^2 for the proton and neutron, respectively.Comment: 10 pages REVTeX, 4 figure