Social Support, Basic Psychological Needs, and Social Well-Being Among Older Cancer Survivors.

This study examined the contribution of social support and satisfaction of basic psychological needs in predicting social well-being among older cancer survivors, from the perspective of self-determination theory. The sample for this study derived from the third wave of the National Survey of Midlife Development in the United States. Participants consisted of 376 cancer survivors who had completed cancer treatment. The results of this study suggested that social support from family members and friends was a significant predictor of social well-being. Satisfaction of the basic psychological needs (autonomy, competence, and relatedness) was a significant predictor of social well-being. The fulfillment of basic psychological needs among older cancer survivors is important to the experience of greater social well-being, a finding that contributes to the development of a dynamic model of motivation, engagement in social activity, and successful reintegration into one's community.

Two Generations of Mother-Child Relationships: A Self-determination Theory Analysis of the Social Situation of Development.

Background: This study used self-determination theory to examine the intergenerational continuity of the social situation of development with a focus on what determines a woman's basic psychological need support for her child. Objective: To assess the relationship between the basic need support a woman received from her own mother, the woman's basic need support toward her own child, and the quality of the woman-child interaction. Design: The scales, "Parent-child interaction" and "Basic Psychological Needs," were administered. Eighty-seven women (29-40 years old) with children age 4-5 years assessed the basic need support provided for them by their mother in childhood and at present, and her estimate of the basic need support she herself provides to her own child. Analyses included descriptive statistics, Wilcoxon signed-rank tests, factor analysis, and multiple linear regression. Results: The ratio of levels of basic need support demonstrated continuity across generations. Intergenerational continuity in the child's basic need support mainly concerns the needs for competence and relatedness: the more they were supported in childhood and are now supported by the woman's mother, the more the woman supports them in her own child today. Such continuity was not found for autonomy support. A woman's own basic need support by her mother, in childhood and currently, and the woman's provision of basic need support for her child predicted most of the woman-child interaction parameters. Conclusion: Intergenerational continuity with respect to provision of basic need support was shown. The woman-child interaction was predicted by basic need support across intergenerational relations.

In-Plate Cryopreservation of 2D and 3D Cell Models: Innovative Tools for Biomedical Research and Preclinical Drug Discovery.

Cell-based assays performed in multiwell plates are utilized in basic and translational research in a variety of cell models. The assembly of these multiwell platforms and their use is often laboratory specific, preventing the standardization of methods and the comparison of outputs across different analytical sites. Moreover, when cell models are based on primary cells with specialized culture requirements, including three-dimensional (3D) cell culture, their complexity and the need for manipulation by experienced operators can add significant cost and introduce long lead times to analysis, both of which are undesirable in any preclinical situation. To address this issue, we explored adaptations of cryopreservation technology that allow cells to be cryopreserved in-plate, ready for use in analysis, and have developed a method applicable to cells from different origins and different culture formats. Here we describe the application of this technology to conventional two-dimensional (2D) monolayers of human mesenchymal stem cells (MSCs) and human macrophages derived from primary monocytes, and to 3D cultures of hepatic organoids, colon organoids, and colon tumor organoids, each presented for cryopreservation in their obligate extracellular matrix. We demonstrated that cell viability, cell physiology, and cytotoxic sensitivity were maintained after cryopreservation, such that the models offer the means to uncouple model assembly from analytical use and to standardize cell models in product form for distribution to end users.

Testing satisfaction of basic psychological needs as a mediator of the relationship between socioeconomic status and physical and mental health.

This research applied self-determination theory to examine the degree to which satisfaction of basic psychological needs for autonomy, relatedness, and competence explained the association between socioeconomic status and physical and mental health outcomes, while controlling for age, exercise, and smoking status. This was a survey research study with 513 full-time employees in professions representative of a hierarchal organization. The results of the structural equation model verify that psychological need satisfaction mediates the inverse association between socioeconomic status and physical and mental health. Self-determination theory contributes to understanding the psychosocial roots of the uneven distribution of health across the socioeconomic gradient.

Predictors of older adults' technology use and its relationship to depressive symptoms and well-being.

OBJECTIVE: To extend the empirical evidence regarding the predictors of older adults' use of information and communications technology (ICT) and to further examine its relationship to depressive symptoms and well-being. METHOD: This cross-sectional study utilized a sample of community-dwelling older adults from the National Health and Aging Trends Study (N = 6,443). Structural equation modeling was used to estimate the effects of predictor variables on ICT use and the effects of use on depressive symptoms and well-being. Tests of moderation by demographic characteristics and level of ICT use were also performed. RESULTS: Socioeconomic status (SES), age, and cognitive function accounted for approximately 60% of the variance in ICT use. SES was a stronger predictor for Blacks/African Americans, whereas cognitive function was a stronger predictor for Whites. ICT use was unrelated to depressive symptoms or well-being. However, it acted as a moderator, such that limitations in activities of daily living (ADLs) was a stronger predictor of depressive symptoms for high ICT users, whereas ill-health was a stronger predictor for non/limited users. DISCUSSION: Findings do not support the claim that ICT use directly enhances mental health or well-being among older adults although it may protect against depressive symptoms for individuals coping with health conditions other than ADL impairments.

Patient evaluation of early discharge after hip arthroplasty: development of a measure and comparison of three centres with differing durations of stay.

OBJECTIVE: We compared patients' evaluation of care between a surgical unit with a rapid discharge policy and two comparison units to test the hypothesis that the centre with rapid discharge has outcomes that are not inferior to those of the comparison sites. DESIGN: Cross-sectional cohort study. SUBJECTS: Consecutive consenting patients undergoing primary hip arthroplasty during 12 months in: a unit that had reduced postoperative stay to median three days; a specialised orthopaedic surgery treatment centre with median stay of five days; a traditional unit with median stay of six days (N = 316, 125, 119, respectively). METHODS: Six weeks postoperatively, patients completed a specially developed questionnaire measuring their evaluation of care and recovery, together with measures of function and quality of life for validation purposes. RESULTS: Factor analysis of questionnaire responses identified two independent components of patients' evaluation: problems in staff care and problems in physical recovery. Neither component was impaired in the unit with rapid discharge: similar proportions of patients reported recovery problems in each site (odds radios (ORs) for the two comparators versus unit with rapid discharge: 0.96, 1.18); and more patients reported care problems in the two comparator sites (ORs 2.97, 2.16). CONCLUSION: Duration of stay after primary hip arthroplasty can be reduced to three days without intensive pre- or postoperative care, without detriment to patient evaluation.

The ideal self at play: the appeal of video games that let you be all you can be.

Video games constitute a popular form of entertainment that allows millions of people to adopt virtual identities. In our research, we explored the idea that the appeal of games is due in part to their ability to provide players with novel experiences that let them "try on" ideal aspects of their selves that might not find expression in everyday life. We found that video games were most intrinsically motivating and had the greatest influence on emotions when players' experiences of themselves during play were congruent with players' conceptions of their ideal selves. Additionally, we found that high levels of immersion in gaming environments, as well as large discrepancies between players' actual-self and ideal-self characteristics, magnified the link between intrinsic motivation and the experience of ideal-self characteristics during play.

Cyclic AMP phosphodiesterase 4D (PDE4D) Tethers EPAC1 in a vascular endothelial cadherin (VE-Cad)-based signaling complex and controls cAMP-mediated vascular permeability.

Vascular endothelial cell (VEC) permeability is largely dependent on the integrity of vascular endothelial cadherin (VE-cadherin or VE-Cad)-based intercellular adhesions. Activators of protein kinase A (PKA) or of exchange protein activated by cAMP (EPAC) reduce VEC permeability largely by stabilizing VE-Cad-based intercellular adhesions. Currently, little is known concerning the nature and composition of the signaling complexes that allow PKA or EPAC to regulate VE-Cad-based structures and through these actions control permeability. Using pharmacological, biochemical, and cell biological approaches we identified and determined the composition and functionality of a signaling complex that coordinates cAMP-mediated control of VE-Cad-based adhesions and VEC permeability. Thus, we report that PKA, EPAC1, and cyclic nucleotide phosphodiesterase 4D (PDE4D) enzymes integrate into VE-Cad-based signaling complexes in human arterial endothelial cells. Importantly, we show that protein-protein interactions between EPAC1 and PDE4D serve to foster their integration into VE-Cad-based complexes and allow robust local regulation of EPAC1-based stabilization of VE-Cad-based adhesions. Of potential translational importance, we mapped the EPAC1 peptide motif involved in binding PDE4D and show that a cell-permeable variant of this peptide antagonizes EPAC1-PDE4D binding and directly alters VEC permeability. Collectively, our data indicate that PDE4D regulates both the activity and subcellular localization of EPAC1 and identify a novel mechanism for regulated EPAC1 signaling in these cells.

Living history in current orthopaedic hip surgery: intrapelvic teflon granuloma after total hip replacement.

The teflon hip arthroplasty design was used by Sir John Charnley in the early 60's but was taken off the market due to high complication rates. A case is reported of an intrapelvic granuloma after total hip arthroplasty following the use of a teflon socket. This appears to be the last surviving patient treated by Sir John Charnley using a Teflon hip socket design.

Using online simulation in child health nurse education.

It is easy to underestimate the complexity of nursing care. Child health nursing students are expected to apply theory to practice and gain competence in a variety of settings. The development of a virtual ward allows the nursing student to practise caring for a child with a fever in the safety of the student's home environment or computer laboratory using learning techniques that help them question their own awareness and the care they have witnessed in the clinical environment. This article explores the development of this simulation and the results of the student evaluation.

The consequences of early discharge after hip arthroplasty for patient outcomes and health care costs: comparison of three centres with differing durations of stay.

OBJECTIVE: To compare outcomes from hip arthroplasty between a surgical unit with a rapid discharge policy and two comparison units to test the hypothesis that the centre with rapid discharge has outcomes that are not inferior to the comparison sites. DESIGN: Prospective cohort study. SUBJECTS: Consecutive consenting patients receiving primary hip arthroplasty during 12 months beginning July 2006 in three UK National Health Service surgical units. One has shortened postoperative stay to median three days; one was a new treatment centre with median stay of five days; the third was a traditional unit with median stay of six days (N = 316, 119, 87, respectively). METHODS: Patients were assessed preoperatively and six weeks postoperatively. The primary indicator of function was the Oxford Hip Score. Additional secondary measures included further self-report indicators of function and quality of life and health service costs. RESULTS: Patient outcome in the unit with rapid discharge was not impaired by comparison with the other sites on any measure: Oxford Hip Score decreased from 49 to 27 in the short-stay unit, from 40 to 30 in the treatment centre and from 43 to 32 in the traditional unit. Cost of arthroplasty was least in the short-stay unit, although there was potential for cost savings in each. CONCLUSION: Short postoperative stay after hip arthroplasty can be achieved without intensive patient preparation or post-discharge care and without compromising short-term patient outcome or increasing health care costs. Longer term follow-up is needed.

Early discharge following hip arthroplasty: patients' acceptance masks doubts and concerns.

OBJECTIVE: To describe patients' experience of accelerated discharge after hip arthroplasty in order to test the acceptability to patients of economically driven shortening of post-operative stay. METHODS: Patients (n = 35) who had received primary total hip replacement up to 12 weeks previously were recruited from two UK orthopaedic units, one of which has pioneered short post-operative stay (3-4 days), and another one of which retains a traditional regimen of discharge after 6-7 days. Patients were interviewed about their experience of care, focusing particularly on their views related to length of stay and with particular attention to patients' well-known tendency to mask critical views of their care. Transcripts were analysed thematically to identify the ways that patients evaluated their care and whether these differed between sites. RESULTS: Patients were primarily concerned with how attentive and informative hospital staff had been and did not refer to length of stay spontaneously. When prompted about this, they did not question their discharge time, although those in the more traditional unit could not countenance more rapid discharge. Patients in the unit with accelerated discharge described concerns about the consequences of early discharge for them or their family, particularly managing pain and mobility problems at home and needing more support. CONCLUSIONS: Patients' traditional beliefs about the necessity of prolonged convalescence are not a barrier to early discharge after hip arthroplasty. Nevertheless, some patients' acceptance of early discharge masks doubts and concerns. More intensive post-operative management may be needed if clinical care is not to suffer.

MEK1 binds directly to betaarrestin1, influencing both its phosphorylation by ERK and the timing of its isoprenaline-stimulated internalization.

betaArrestin is a multifunctional signal scaffold protein. Using SPOT immobilized peptide arrays, coupled with scanning alanine substitution and mutagenesis, we show that the MAPK kinase, MEK1, interacts directly with betaarrestin1. Asp(26) and Asp(29) in the N-terminal domain of betaarrestin1 are critical for its binding to MEK1, whereas Arg(47) and Arg(49) in the N-terminal domain of MEK1 are critical for its binding to betaarrestin1. Wild-type FLAG-tagged betaarrestin1 co-immunopurifies with MEK1 in HEKB2 cells, whereas the D26A/D29A mutant does not. ERK-dependent phosphorylation at Ser(412) was compromised in the D26A/D29A-betaarrestin1 mutant. A cell-permeable, 25-mer N-stearoylated betaarrestin1 peptide that encompassed the N-domain MEK1 binding site blocked betaarrestin1/MEK1 association in HEK cells and recapitulated the altered phenotype seen with the D26A/D29A-betaarrestin1 in compromising the ERK-dependent phosphorylation of betaarrestin1. In addition, the MEK disruptor peptide promoted the ability of betaarrestin1 to co-immunoprecipitate with endogenous c-Src and clathrin, facilitating the isoprenaline-stimulated internalization of the beta(2)-adrenergic receptor.

EPAC and PKA allow cAMP dual control over DNA-PK nuclear translocation.

We identify a compartmentalized signaling system that identifies a functional role for the GTP exchange factor, exchange protein activated by cAMP (EPAC) coupled to Rap2 in the nucleus. In this system, cAMP regulates the nuclear/cytoplasmic trafficking of DNA-dependent protein kinase (DNA-PK), a critical kinase that acts to repair double-stranded breaks (DSBs) in damaged DNA and to phosphorylate the cell survival kinase, PKB/Akt. Intersecting regulatory inputs for cAMP employ EPAC to transduce positive effects, namely the Rap2-dependent nuclear exit and activation of DNA-PK, whereas protein kinase A (PKA) provides the negative input by antagonizing these actions. We identify this as a compartmentalized regulatory system where modulation of cAMP input into the stimulatory, EPAC and inhibitory, PKA intersecting arms is provided by spatially discrete, cAMP degradation systems. The distribution of DNA-PK between nuclear and cytoplasmic compartments can thus potentially be influenced by relative inputs of cAMP signaling through the EPAC and PKA pathways. Through this signaling system EPAC activation can thereby impact on the Ser-473 phosphorylation status of PKB/Akt and the repair of etoposide-induced DSBs.

In cardiac myocytes, cAMP elevation triggers the down-regulation of transcripts and promoter activity for cyclic AMP phosphodiesterase-4A10 (PDE4A10).

Transcripts for the PDE4A10 cyclic AMP phosphodiesterase isoform are present in a wide variety of rat tissues including the heart. Sequence comparisons between the putative human and mouse promoters revealed a number of conserved regions including both an Sp1 and a CREB-binding site. The putative mouse PDE4A10 promoter was amplified from genomic DNA and sub-cloned into a luciferase reporter vector for investigation of activity in neonatal cardiac myocytes. Transfection with this construct identified a high level of luciferase expression in neonatal cardiac myocytes. Surprisingly, this activity was down-regulated by elevation of intracellular cAMP through a process involving PKA, but not EPAC, signalling. Such inhibition of the rodent PDE4A10 promoter activity in response to elevated cAMP levels is in contrast to the PDE4 promoters so far described. Site-directed mutagenesis revealed that the Sp1 binding site at promoter position -348 to -336 is responsible for the basal constitutive expression of murine PDE4A10. The conserved CREB-binding motif at position -370 to -363 also contributes to basal promoter activity but does not in itself confer cAMP inhibition upon the PDE4A10 promoter. EMSA analysis confirmed the authenticity of CREB and Sp1 binding sites. The transcriptional start site was identified to be an adenine residue at position -55 in the mouse PDE4A10 promoter. We present evidence that this novel down-regulation of PDE4A10 is mediated by the transcription factor ICER in a PKA dependent manner. The pool of cAMP in cardiac myocytes that down-regulates PDE4A10 is regulated by beta-adrenoceptor coupled adenylyl cyclase activity and via hydrolysis determined predominantly by the action of PDE4 (cAMP phosphodiesterase-4) and not PDE3 (cAMP phosphodiesterase-3). We suggest that increased cAMP may remodel cAMP-mediated signalling events by not only increasing the expression of specific PDE4 cAMP phosphodiesterases but also by down-regulating specific isoforms, such as is shown here for PDE4A10 in cardiac myocytes.

Tyrosine 302 in RACK1 is essential for insulin-like growth factor-I-mediated competitive binding of PP2A and beta1 integrin and for tumor cell proliferation and migration.

Insulin-like growth factor (IGF)-I regulates a mutually exclusive interaction of PP2A and beta1 integrin with the WD repeat scaffolding protein RACK1. This interaction is required for the integration of IGF-I receptor (IGF-IR) and adhesion signaling. Here we investigated the nature of the binding site for PP2A and beta1 integrin in RACK1. A WD7 deletion mutant of RACK1 did not associate with PP2A but retained some interaction with beta1 integrin, whereas a WD6/WD7 mutant lost the ability to bind to both PP2A and beta1 integrin. Using immobilized peptide arrays representing the entire RACK1 protein, we identified a common cluster of amino acids (FAGY) at positions 299-302 within WD7 of RACK1 which were essential for binding of both PP2A and beta1 integrin to RACK1. PP2A showed a higher level of association with a peptide in which Tyr-302 was phosphorylated compared with an unphosphorylated peptide, whereas beta1 integrin binding was not affected by phosphorylation. RACK1 mutants in which either the FAGY cluster or Tyr-302 were mutated to AAAF, or Phe, respectively, did not interact with either PP2A or beta1 integrin. These mutants were unable to rescue the decrease in PP2A activity caused by suppression of RACK1 in MCF-7 cells with small interfering RNA. MCF-7 cells and R+ (IGF-IR-overexpressing fibroblasts) expressing these mutants exhibited decreased proliferation and migration, whereas R- cells (IGF-IR null fibroblasts) were unaffected. Taken together, the data demonstrate that Tyr-302 in RACK1 is required for interaction with PP2A and beta1 integrin, for regulation of PP2A activity, and for IGF-I-mediated cell migration and proliferation.

Computer-assisted intervention improves patient-centered diabetes care by increasing autonomy support.

OBJECTIVE: To determine if a patient-centered, computer-assisted diabetes care intervention increased perceived autonomy support, perceived competence (from self-determination theory), and if these constructs mediated the effect of the intervention on ADA/NCQA recommended diabetes care outcomes. DESIGN: A randomized controlled trial of 866 adult type 2 diabetes patients in heterogeneous primary care settings in Colorado. MAIN OUTCOME MEASURES: Perceived autonomy support, perceived competence, patient satisfaction, glycemic control (HbA1c), ratio of total to HDL cholesterol, diabetes distress, and depressive symptoms. RESULTS: The computer-assisted intervention increased patient perception of autonomy support relative to a computer-based control condition ( p = .05). Change in perceived competence partially mediated the effects of increased autonomy support on the change in lipids, diabetes distress, and depressive symptoms. The construct of autonomy support was found to be separate from that of patient satisfaction. CONCLUSIONS: A patient-centered, computer-assisted intervention was effective in improving diabetes self-management outcomes, in part, because it increased patients' perception that their autonomy was supported which changed perceived competence. These findings support the self-determination model for health behavior change and the chronic care model and support the further study of the use of these technologies to motivate patients to improve their health outcomes.

Dynamic regulation, desensitization, and cross-talk in discrete subcellular microdomains during beta2-adrenoceptor and prostanoid receptor cAMP signaling.

Dynamic and localized actions of cAMP are central to the generation of discrete cellular events in response to a range of G(s)-coupled receptor agonists. In the present study we have employed a cyclic nucleotide-gated channel sensor to report acute changes in cAMP in the restricted cellular microdomains adjacent to two different G(s)-coupled receptor pathways, beta(2)-adrenoceptors and prostanoid receptors that are expressed endogenously in HEK293 cells. We probed by either selective small interference RNA-mediated knockdown or dominant negative overexpression the contribution of key signaling components in the rapid attenuation of the local cAMP signaling and subsequent desensitization of each of these G-protein-coupled receptor signaling pathways immediately following receptor activation. Direct measurements of cAMP changes just beneath the plasma membrane of single HEK293 cells reveal novel insights into key regulatory roles provided by protein kinase A-RII, beta-arrestin2, cAMP phosphodiesterase-4D3, and cAMP phosphodiesterase-4D5. We provide new evidence for distinct modes of cAMP down-regulation in these two G(s)-linked pathways and show that these distinct G-protein-coupled receptor signaling systems are subject to unidirectional, heterologous desensitization that allows for limited cross-talk between distinct, dynamically regulated pools of cAMP.

p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway.

Clearance of fibrin through proteolytic degradation is a critical step of matrix remodeling that contributes to tissue repair in a variety of pathological conditions, such as stroke, atherosclerosis, and pulmonary disease. However, the molecular mechanisms that regulate fibrin deposition are not known. Here, we report that the p75 neurotrophin receptor (p75(NTR)), a TNF receptor superfamily member up-regulated after tissue injury, blocks fibrinolysis by down-regulating the serine protease, tissue plasminogen activator (tPA), and up-regulating plasminogen activator inhibitor-1 (PAI-1). We have discovered a new mechanism in which phosphodiesterase PDE4A4/5 interacts with p75(NTR) to enhance cAMP degradation. The p75(NTR)-dependent down-regulation of cAMP results in a decrease in extracellular proteolytic activity. This mechanism is supported in vivo in p75(NTR)-deficient mice, which show increased proteolysis after sciatic nerve injury and lung fibrosis. Our results reveal a novel pathogenic mechanism by which p75(NTR) regulates degradation of cAMP and perpetuates scar formation after injury.

PGE(1) stimulation of HEK293 cells generates multiple contiguous domains with different [cAMP]: role of compartmentalized phosphodiesterases.

There is a growing appreciation that the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway is organized to form transduction units that function to deliver specific messages. Such organization results in the local activation of PKA subsets through the generation of confined intracellular gradients of cAMP, but the mechanisms responsible for limiting the diffusion of cAMP largely remain to be clarified. In this study, by performing real-time imaging of cAMP, we show that prostaglandin 1 stimulation generates multiple contiguous, intracellular domains with different cAMP concentration in human embryonic kidney 293 cells. By using pharmacological and genetic manipulation of phosphodiesterases (PDEs), we demonstrate that compartmentalized PDE4B and PDE4D are responsible for selectively modulating the concentration of cAMP in individual subcellular compartments. We propose a model whereby compartmentalized PDEs, rather than representing an enzymatic barrier to cAMP diffusion, act as a sink to drain the second messenger from discrete locations, resulting in multiple and simultaneous domains with different cAMP concentrations irrespective of their distance from the site of cAMP synthesis.