Nurses' models of spiritual care: A cross-sectional survey of American nurses.

OBJECTIVES: Despite there being many models for how spiritual care should be provided, the way nurses actually provide spiritual care often differs from these models. Based on the premise that the way a person enacts their work role is related to how they understand that role, this study aims to describe the qualitatively different ways that nurses understand their spiritual care role. METHODS: A convenience sample of 66 American nurses completed an anonymous, online questionnaire about what spiritual care means for them and what they generally do to provide spiritual care. Their responses were analyzed phenomenographically. RESULTS: Four qualitatively different ways of understanding emerged: active management of the patient's experience, responsive facilitation of patient's wishes, accompaniment on the patient's dying journey, and empowering co-action with the patient. Each understanding was found to demonstrate a specific combination of 5 attributes that described the spiritual care role: nurse directivity, the cues used for spiritual assessment, and the nurse's perception of intimacy, the patient, and the task. SIGNIFICANCE OF RESULTS: The findings of this study may explain why nurses vary in their spiritual care role and can be used to assess and develop competence in spiritual care.

Australian Patient Preferences for Discussing Spiritual Issues in the Hospital Setting: An Exploratory Mixed Methods Study.

While there is high patient acceptance for clinical staff discussing issues regarding spirituality with hospital inpatients, it is not clear which staff member patients prefer for these discussions. This unique exploratory study investigated inpatient preferences regarding which staff member should raise the topic of spirituality. A cross-sectional survey was conducted with inpatients at six hospitals in Sydney, Australia (n = 897), with a subset invited to participate in qualitative interviews (n = 41). Pastoral care staff (32.9%) were the preferred staff members with whom to discuss spiritual issues, followed by doctors (22.4%). Qualitative findings indicated that individual characteristics of the staff member are more important than their role.

Measurement of Spiritual Wellbeing in an Australian Hospital Population Using the Functional Assessment of Chronic Illness Therapy: Spiritual Wellbeing Scale (FACIT-Sp-12).

Spiritual wellbeing is known to be a predictor of increased patient coping in hospital settings. Therefore, access to a valid and reliable measure of spiritual wellbeing amongst general hospital patients is highly recommended. The aim of this study was to investigate the dimensionality, reliability, and validity of the Functional Assessment of Chronic Illness Therapy Spiritual Wellbeing scale (FACIT-Sp-12) in a heterogeneous cohort of hospital patients. A cross-sectional survey was administered to 897 adult patients across six hospitals in Sydney, Australia. Confirmatory factor analysis for the three-factor FACIT-12-Sp indicated a poor fit, but after removal of Item 12, the three-factor FACIT-11-Sp presented a good fit to the data. Reliability testing indicated acceptable to good internal consistency. Validity was supported by statistically significant differences between patients who considered themselves 'both spiritual and religious' and 'not religious or spiritual'. While some caution should be taken when using the FACIT-Sp due to several limitations, nevertheless, in a general hospital population in Australia, the three-factor FACIT-11-Sp indicated good dimensionality, reliability, and validity.

Australian Patient Preferences for the Introduction of Spirituality into their Healthcare Journey: A Mixed Methods Study.

While patients value engagement concerning their spirituality as a part of holistic healthcare, there is little evidence regarding the preferred way to engage in discussions about spirituality. This study investigated inpatient preferences regarding how they would like spirituality to be raised in the hospital setting. A cross-sectional survey was conducted with inpatients at six hospitals in Sydney, Australia (n = 897), with a subset invited to participate in qualitative interviews (n = 41). There was high approval for all proposed spiritual history prompts (94.0-99.8%). In interviews, the context dictated the appropriateness of discussions. Findings indicated a high level of patient acceptability for discussing spirituality in healthcare. Further research and more detailed analysis is required and proposed to be undertaken.

Factors influencing nurse spiritual care practices at the end of life: A systematic review.

OBJECTIVES: The aim was to identify determinants of nurse spiritual/existential care practices toward end-of-life patients. Nurses can play a significant role in providing spiritual/existential care, but they actually provide this care less frequently than desired by patients. METHODS: A systematic search was performed for peer-reviewed articles that reported factors that influenced nurses' spiritual/existential care practices toward adult end-of-life patients. RESULTS: The review identified 42 studies and included the views of 4,712 nurses across a range of hospital and community settings. The most frequently reported factors/domains that influenced nurse practice were patient-related social influence, skills, social/professional role and identity, intentions and goals, and environmental context and resources. SIGNIFICANCE OF RESULTS: A range of personal, organizational, and patient-related factors influence nurse provision of spiritual/existential care to end-of-life patients. This complete list of factors can be used to gauge a unit's conduciveness to nurse provision of spiritual/existential care and can be used as inputs to nurse competency frameworks.

Polarity of Hydrated Phosphatidylcholine Headgroups.

The headgroup (H) stratum (sometimes called the polar region) of membrane bilayers is a relevant yet poorly understood solvation phase for small molecules and macromolecules interacting with the membranes. Solvation of compounds in bilayer strata is characterized experimentally by wide- and small-angle X-ray scattering, neutron diffraction, and various NMR techniques. The quantification is tedious and only available for a limited set of small molecules. Our recently published model of liposome partitioning of small molecules shows that solvation of compounds in the H-stratum of fluid phosphatidylcholine (PC) bilayers correlates well with their solvation in hydrated diacetyl phosphatidylcholine (DAcPC), and solvation in the core (C) depends in a similar way on that in n-hexadecane. These two correlations became a basis for a model describing the location of compounds in the H- and C-strata and at the connecting interface as a nonlinear function of the fragment solvation characteristics of the compounds. In this study, refractivity of hydrated DAcPC phases with varying water contents was measured and polarity was determined using the steady-state fluorescence of indole and Nile Red. The results were compared with the published data obtained by other techniques for PC bilayers in liposomes or on solid supports. The demonstrated qualitative agreement, as well as the polarity and refractivity dependencies on the DAcPC concentration, supports the suitability of hydrated DAcPC as the H-stratum surrogate. Interestingly, depending on hydrations typical for the H-strata of fluid PC bilayers, the dielectric constant could decrease significantly from 31.0 to 7.3 for 16 and 8 water molecules per headgroup, respectively. Although additional experiments are needed for confirmation, this observation could help set proper dielectric constant magnitudes in continuum-based computational models of accumulation and crossing of the PC bilayers with varying hydration levels thanks to the temperature or the structure of fatty acid chains.

Structure-based prediction of drug distribution across the headgroup and core strata of a phospholipid bilayer using surrogate phases.

Solvation of drugs in the core (C) and headgroup (H) strata of phospholipid bilayers affects their physiological transport rates and accumulation. These characteristics, especially a complete drug distribution profile across the bilayer strata, are tedious to obtain experimentally, to the point that even simplified preferred locations are only available for a few dozen compounds. Recently, we showed that the partition coefficient (P) values in the system of hydrated diacetyl phosphatidylcholine (DAcPC) and n-hexadecane (C16), as surrogates of the H- and C-strata of the bilayer composed of the most abundant mammalian phospholipid, PC, agree well with the preferred bilayer location of compounds. High P values are typical for lipophiles accumulating in the core, and low P values are characteristic of cephalophiles preferring the headgroups. This simple pattern does not hold for most compounds, which usually have more even distribution and may also accumulate at the H/C interface. To model complete distribution, the correlates of solvation energies are needed for each drug state in the bilayer: (1) for the H-stratum it is the DAcPC/W P value, calculated as the ratio of the C16/W and C16/DAcPC (W for water) P values; (2) for the C-stratum, the C16/W P value; (3) for the H/C interface, the P values for all plausible molecular poses are characterized using the fragment DAcPC/W and C16/W solvation parameters for the parts of the molecule embedded in the H- and C-strata, respectively. The correlates, each scaled by two Collander coefficients, were used in a nonlinear, mass-balance based model of intrabilayer distribution, which was applied to the easily measurable overall P values of compounds in the DMPC (M = myristoyl) bilayers and monolayers as the dependent variables. The calibrated model for 107 neutral compounds explains 94% of experimental variance, achieves similar cross-validation levels, and agrees well with the nontrivial, experimentally determined bilayer locations for 27 compounds. The resulting structure-based prediction system for intrabilayer distribution will facilitate more realistic modeling of passive transport and drug interactions with those integral membrane proteins, which have the binding sites located in the bilayer, such as some enzymes, influx and efflux transporters, and receptors. If only overall bilayer accumulation is of interest, the 1-octanol/W P values suffice to model the studied set.

Giving Voice to Values: an undergraduate nursing curriculum project.

Among the competency standards stipulated by the Australian Nursing and Midwifery Council for graduating students are competencies in moral and ethical decision making and ethics education within professions such as nursing has traditionally focussed on these competencies, on raising ethical awareness and developing skills of analysis and reasoning. However, ethics education in tertiary settings places less emphasis on developing students' capacities to act on their values. This paper explains and explores the adoption of Dr. Mary Gentile's curriculum (the Giving Voice to Values curriculum).which specifically focuses on developing students' capacities to act on their values. The curriculum (Gentile, 2010) assists students and professionals to explore, script and rehearse responses which build upon their capacity to respond in accordance with their own values in complex workplace settings in which they face conflicts of value and belief. The paper firstly examines the theoretical underpinnings of the Giving Voice to Values (GVV) curriculum. It then presents the integration and evaluation phase of a Project inspired by the GVV methodology, using a case study approach within two areas of an undergraduate nursing curriculum. As a pilot project, this initiative has provided signposts to further curriculum development and to research pathways within the UNDA School of Nursing, by highlighting students' uncertainties regarding their own professional values, and their intense struggles to voice their values within health care contexts.

Structural determinants of drug partitioning in surrogates of phosphatidylcholine bilayer strata.

The knowledge of drug concentrations in bilayer headgroups, core, and at the interface between them is a prerequisite for quantitative modeling of drug interactions with many membrane-bound transporters, metabolizing enzymes and receptors, which have the binding sites located in the bilayer. This knowledge also helps understand the rates of trans-bilayer transport because balanced interactions of drugs with the bilayer strata lead to high rates, while excessive affinities for any stratum cause a slowdown. Experimental determination of bilayer location is so tedious and costly that the data are only available for some fifty compounds. To extrapolate these valuable results to more compounds at a higher throughput, surrogate phases have been used to obtain correlates of the drug affinities for individual strata. We introduced a novel system, consisting of a diacetyl phosphatidylcholine (DAcPC) solution with the water content of the fluid bilayer as the headgroup surrogate and n-hexadecane (C16) representing the core. The C16/DAcPC partition coefficients were measured for 113 selected compounds, containing structural fragments that are frequently occurring in approved drugs. The data were deconvoluted into the ClogP-based fragment solvation characteristics and processed using a solvatochromic correlation. Increased H-bond donor ability and excess molar refractivity of compounds promote solvation in the DAcPC phase as compared to bulk water, contrary to H-bond acceptor ability, dipolarity/polarizability, and volume. The results show that aromates have more balanced distribution in bilayer strata, and thus faster trans-bilayer transport, than similar alkanes. This observation is in accordance with the frequent occurrence of aromatic rings in approved drugs and with the role of rigidity of drug molecules in promoting intestinal absorption. Bilayer locations, predicted using the C16/DAcPC system, are in excellent agreement with available experimental data, in contrast to other surrogate systems.

Structural determinants of drug partitioning in n-hexadecane/water system.

Surrogate phases have been widely used as correlates for modeling transport and partitioning of drugs in biological systems, taking advantage of chemical similarity between the surrogate and the phospholipid bilayer as the elementary unit of biological phases, which is responsible for most of the transport and partitioning. Solvation in strata of the phospholipid bilayer is an important drug characteristic because it affects the rates of absorption and distribution, as well as the interactions with the membrane proteins having the binding sites located inside the bilayer. The bilayer core can be emulated by n-hexadecane (C16), and the headgroup stratum is often considered a hydrophilic phase because of the high water content. Therefore, we tested the hypothesis that the C16/water partition coefficients (P) can predict the bilayer locations of drugs and other small molecules better than other surrogate systems. Altogether 514 PC16/W values for nonionizable (458) and completely ionized (56) compounds were collected from the literature or measured, when necessary. With the intent to create a fragment-based prediction system, the PC16/W values were factorized into the fragment solvation parameters (f) and correction factors based on the ClogP fragmentation scheme. A script for the PC16/W prediction using the ClogP output is provided. To further expand the prediction system and reveal solvation differences, the fC16/W values were correlated with their more widely available counterparts for the 1-octanol/water system (O/W) using solvatochromic parameters. The analysis for 50 compounds with known bilayer location shows that the available and predicted PC16/W and PO/W values alone or the PC16/O values representing their ratio do not satisfactorily predict the preference for drug accumulation in bilayer strata. These observations indicate that the headgroups stratum, albeit well hydrated, does not have solvation characteristics similar to water and is also poorly described by the O/W partition characteristics.

Personhood, harm and interest: a reply to Alberto Giubilini and Francesca Minerva.

In the article 'After-birth abortion: why should the baby live?' arguments are made in favour of the moral permissibility of intentionally killing newborn infants, under particular conditions. Here we argue that their arguments are based on an indefensible view of personhood, and we question the logic of harm and interest that informs their arguments. Furthermore, we argue that the conclusions here are so contrary to ordinary moral intuitions that the argument and conclusions based upon it-including those which defend more mainstream methods of abortion-should be treated with immediate suspicion.

Comparison of child and parent satisfaction ratings of ambulatory pediatric subspecialty care.

INTRODUCTION: Opinions about satisfaction with care are rarely solicited from children. This study's purpose was to compare children's ratings of patient satisfaction with outpatient care to ratings given by parents. METHOD: This descriptive and comparative survey study compared responses of a convenience sample of children and adolescents (n = 116) who received care at two metropolitan pediatric subspecialty clinics with their parents' responses (n = 115). Ratings were obtained using the "Satisfaction with Child Healthcare Survey," an instrument adapted with permission from the "Kids Count Survey" developed at McMaster Health Center in Ontario, Canada. Additionally, three open-ended questions were solicited and analyzed for major themes. RESULTS: There was moderate significant correlation between child-teen and parent scores. Parents rated care significantly higher than did the children. Children's responses to open-ended questions varied somewhat from their parents' opinions on various aspects of clinic visits. DISCUSSION: Findings suggested that having parents evaluate children's care may not accurately represent the views of children and teens. Findings supported children and teens' ability to provide valuable perceptions about care that can inform clinic improvement processes.

The effect of pH dependence of antibody-antigen interactions on subcellular trafficking dynamics.

A drawback of targeting soluble antigens such as cytokines or toxins with long-lived antibodies is that such antibodies can prolong the half-life of the target antigen by a "buffering" effect. This has motivated the design of antibodies that bind to target with higher affinity at near neutral pH relative to acidic endosomal pH (~pH 6.0). Such antibodies are expected to release antigen within endosomes following uptake into cells, whereas antibody will be recycled and exocytosed in FcRn-expressing cells. To understand how the pH dependence of antibody-antigen interactions affects intracellular trafficking, we generated three antibodies that bind IL-6 with different pH dependencies in the range pH 6.0-7.4. The behavior of antigen in the presence of these antibodies has been characterized using a combination of fixed and live cell fluorescence microscopy. As the affinity of the antibody:IL-6 interaction at pH 6.0 decreases, an increasing amount of antigen dissociates from FcRn-bound antibody in early and late endosomes, and then enters lysosomes. Segregation of antibody and FcRn from endosomes in tubulovesicular transport carriers (TCs) into the recycling pathway can also be observed in live cells, and the extent of IL-6 association with TCs correlates with increasing affinity of the antibody:IL-6 interaction at acidic pH. These analyses result in an understanding, in spatiotemporal terms, of the effect of pH dependence of antibody-antigen interactions on subcellular trafficking and inform the design of antibodies with optimized binding properties for antigen elimination.

Developing intrabodies for the therapeutic suppression of neurodegenerative pathology.

Many neurodegenerative diseases have misfolded proteins as a primary occurrence in pathogenesis. A combination of antibody and genetic engineering has emerged as a powerful tool for developing reagents that specifically target the misfolding process itself, and/or abnormal interactions of the misfolded protein species. This review focuses on the selection and testing of intracellular antibody fragments (intrabodies), with a particular focus on Huntington's disease (HD) and Parkinson's disease (PD), both of which show prominent intracellular protein aggregates in affected neurons. The most dramatic advances are in HD, where in vivo efficacy of intrabodies has been demonstrated. Targets in other neurodegenerative disorders, including Alzheimer's disease and prion diseases, are noted more briefly, with an emphasis on the potential for intracellular manipulations. Given the specificity and versatility of antibody-based reagents, the wide range of options for conformational and post-translationally-modified targets, and the recent improvement in gene delivery, this should be a fertile field for 21(st) century pharmacology.

An scFv intrabody against the nonamyloid component of alpha-synuclein reduces intracellular aggregation and toxicity.

Prevention of abnormal misfolding and aggregation of alpha synuclein (syn) protein in vulnerable neurons should be viable therapeutic strategies for reducing pathogenesis in Parkinson's disease. The nonamyloid component (NAC) region of alpha-syn shows strong tendencies to form beta-sheet structures, and deletion of this region has been shown to reduce aggregation and toxicity in vitro and in vivo. The binding of a molecular species to this region may mimic the effects of such deletions. Single-chain variable fragment (scFv) antibodies retain the binding specificity of antibodies and, when genetically manipulated to create high-diversity libraries, allow in vitro selection against peptides. Accordingly, we used a yeast surface display library of an entire naive repertoire of human scFv antibodies to select for binding to a NAC peptide. Candidate scFv antibodies (after transfer to mammalian expression vectors) were screened for viability in a neuronal cell line by transient cotransfection with A53T mutant alpha-syn. This provided a ranking of the protective efficacies of the initial panel of intracellular antibodies (intrabodies). High steady-state expression levels and apparent conformational epitope binding appeared more important than in vitro affinity in these assays. None of the scFv antibodies selected matched the sequences of previously reported anti-alpha-syn scFv antibodies. A stable cell line expressing the most effective intrabody, NAC32, showed highly significant reductions in abnormal aggregation in two separate models. Recently, intrabodies have shown promising antiaggregation and neuroprotective effects against misfolded mutant huntingtin protein. The NAC32 study extends such work significantly by utilizing information about the pathogenic capacity of a specific alpha-syn region to offer a new generation of in vitro-derived antibody fragments, both for further engineering as direct therapeutics and as a tool for rational drug design for Parkinson's disease.

Dominant role of copper in the kinetic stability of Cu/Zn superoxide dismutase.

Mutations in Cu/Zn superoxide dismutase (SOD) are involved in some cases of familial amyotrophic lateral sclerosis, and it appears that misfolding and aggregation, perhaps mediated by abnormal binding or loss of copper (Cu) and/or zinc (Zn), may play a pathological role. It is known that the absence of both metals kinetically destabilizes wild type and mutant SOD leading to a 60-fold increase in their rate of unfolding. Here, the individual contributions of Cu and Zn to the kinetic stability of SOD were investigated, and the results show that Cu plays a greater role. Thus, the deficiency of Cu or Zn, especially the former, will compromise the kinetic stability of SOD, thereby increasing the probability that pathogenic mutants and even the WT protein may misfold and self-assemble into toxic species.

Kinetic stability of Cu/Zn superoxide dismutase is dependent on its metal ligands: implications for ALS.

Over 100 mutants of the enzyme Cu/Zn superoxide dismutase (SOD) have been implicated in the neurodegenerative disease familial amyotrophic lateral sclerosis (FALS). Growing evidence suggests that the aggregation of SOD mutants may play a causative role in FALS and that aberrant copper chemistry, decreased thermodynamic stability, and decreased affinity for metals may contribute independently or synergistically to this process. Since the loss of the copper and zinc ions significantly decreases the thermodynamic stability of SOD, it is expected that this would also decrease its kinetic stability, thereby facilitating partial or global unfolding transitions that may lead to misfolding and aggregation. Here we used wild-type (WT) SOD and five FALS-related mutants (G37R, H46R, G85R, D90A, and L144F) to show that the metals contribute significantly to the kinetic stability of the protein, with demetalated (apo) SOD showing acid-induced unfolding rates about 60-fold greater than the metalated (holo) protein. However, the unfolding rates of SOD WT and mutants were similar to each other in both the holo and apo states, indicating that regardless of the effect of mutation on thermodynamic stability, the kinetic barrier toward SOD unfolding is dependent on the presence of metals. Thus, these results suggest that pathogenic SOD mutations that do not significantly alter the stability of the protein may still lead to SOD aggregation by compromising its ability to bind or retain its metals and thereby decrease its kinetic stability. Furthermore, the mutant-like decrease in the kinetic stability of apo WT SOD raises the possibility that the loss of metals in WT SOD may be involved in nonfamilial forms of ALS.