Posttraumatic growth in family members living with a relative diagnosed with schizophrenia

Family members living with a relative diagnosed with schizophrenia have reported challenges and traumatic stressors, as well as perceived benefits and personal growth. This study explored factors associated with posttraumatic growth (PTG) within such families. Personality, stress, coping, social support and PTG were assessed in 110 family members. Results revealed that a multiplicative mediational path model with social support and emotional or instrumental coping strategies as multi-mediators had a significant indirect effect on the relationship between extraversion and PTG. Clinically relevant concepts that map onto the multi-mediator model are discussed, translating these findings into clinical practice to facilitate naturally occurring PTG processes.

Bcl-X(L) translocation in renal tubular epithelial cells in vitro protects distal cells from oxidative stress

BACKGROUND: The molecular pathogenesis of different sensitivities of the renal proximal and distal tubular cell populations to ischemic injury, including ischemia-reperfusion (IR)-induced oxidative stress, is not well-defined. An in vitro model of oxidative stress was used to compare the survival of distal [Madin-Darby canine kidney (MDCK)] and proximal [human kidney-2 (HK-2)] renal tubular epithelial cells, and to analyze for links between induced cell death and expression and localization of selected members of the Bcl-2 gene family (anti-apoptotic Bcl-2 and Bcl-X(L), pro-apoptotic Bax and Bad). METHODS: Cells were treated with 1 mmol/L hydrogen peroxide (H2O2) or were grown in control medium for 24 hours. Cell death (apoptosis) was quantitated using defined morphological criteria. DNA gel electrophoresis was used for biochemical identification. Protein expression levels and cellular localization of the selected Bcl-2 family proteins were analyzed (Western immunoblots, densitometry, immunoelectron microscopy). RESULTS: Apoptosis was minimal in control cultures and was greatest in treated proximal cell cultures (16.93 +/- 4.18% apoptosis) compared with treated distal cell cultures (2.28 +/- 0.85% apoptosis, P < 0.001). Endogenous expression of Bcl-X(L) and Bax, but not Bcl-2 or Bad, was identified in control distal cells. Bcl-X(L) and Bax had nonsignificant increases (P> 0.05) in these cells. Bcl-2, Bax, and Bcl-X(L), but not Bad, were endogenously expressed in control proximal cells. Bcl-X(L) was significantly decreased in treated proximal cultures (P < 0.05), with Bax and Bcl-2 having nonsignificant increases (P> 0.05). Immunoelectron microscopy localization indicated that control and treated but surviving proximal cells had similar cytosolic and membrane localization of the Bcl-2 proteins. In comparison, surviving cells in the treated distal cultures showed translocation of Bcl-X(L) from cytosol to the mitochondria after treatment with H2O2, a result that was confirmed using cell fractionation and analysis of Bcl-X(L) expression levels of the membrane and cytosol proteins. Bax remained distributed evenly throughout the surviving distal cells, without particular attachment to any cellular organelle. CONCLUSION: The results indicate that in this in vitro model, the increased survival of distal compared with proximal tubular cells after oxidative stress is best explained by the decreased expression of anti-apoptotic Bcl-X(L) in proximal cells, as well as translocation of Bcl-X(L) protein to mitochondria within the surviving distal cells.

The Thoughts Questionnaire (TQ) for family caregivers of people with dementia

Objectives: To develop a new measure of dysfunctional thoughts for family caregivers of people living with dementia. These thoughts can contribute to negative outcomes, but they may be modifiable. Method: A stepwise process was used to develop the Thoughts Questionnaire, commencing with item generation, concept mapping, and pilot testing in a sample of professional and nonprofessional caregivers of people with dementia (n = 18). Next, an independent sample of 35 family caregivers of people with dementia (30 female; M age = 64.30, standard deviation = 10.65) completed: (a) the Thoughts Questionnaire; (b) an existing measure of dysfunctional thoughts, the Dementia Thoughts Caregivers Questionnaire; and (c) separate validated measures of depressive symptoms, caregiver stress, and coping, respectively. Results: The level of agreement with dysfunctional thought statements from the Dementia Thoughts Caregivers Questionnaire and Thoughts Questionnaire was low. However, a small number of Thoughts Questionnaire statements were strongly endorsed by over 85% of the sample. Both dysfunctional thought measures had adequate reliability, but total scores were not significantly intercorrelated (r = .287, p = .095). Only the Thoughts Questionnaire was significantly, positively correlated with most caregiver stress measures. Thoughts Questionnaire items required a much lower reading level than the Dementia Thoughts Caregivers Questionnaire items. Discussion: This study provides preliminary data on a tool for assessing the negative role-related thoughts that family caregivers of people with dementia may experience. Given that these thoughts are implicated in depression but they may be modified, the capacity to identify dysfunctional thoughts may prove useful in caregiver support programs.

“They are like family”: The emotional cost experienced by nurses when caring for haemodialysis patients

Background Haemodialysis (HD) nursing is characterised by frequent, intense interactions with patients over long periods of time resulting in a unique nurse-patient relationship. Due to the life-limiting nature of end-stage renal failure, nurses are likely to have repeated exposures to the death of patients with whom they have formed relationships. Repeated exposure to patient death translates into frequent grief experiences. There is scant literature on the psychological impact of patient death for nurses working in the HD setting. Aims To explore HD nurses experiences of patient death and coping mechanisms used. Methods A sequential mixed method study investigating job satisfaction, stress and burnout found that HD nurses had high levels of stress and burnout. These results were explored in more detail during 8 semi-structured interviews with HD nurses. Interviews were audio-recorded, transcribed verbatim and subjected to thematic analysis. Results Three themes were identified that highlight the stress experienced by nurses when a haemodialysis patient dies. The first theme, “quazi-family” describes the close relationship which forms between nurses and patients. The “complicated grief” theme outlines the impact of death on HD nurses, and the final theme, “remembrance” explains some of the coping mechanisms used in the grieving process. Conclusion Nurses develop individual coping mechanisms to accommodate the grief and loss experienced when a “close” patient dies. The grieving process caused by the death of patient’s needs to be recognised by nurses and nurse managers as causing psychological stress and strain.

Randomized clinical trial of the timing it right stroke family support program: Research protocol

Background Family caregivers provide invaluable support to stroke survivors during their recovery, rehabilitation, and community re-integration. Unfortunately, it is not standard clinical practice to prepare and support caregivers in this role and, as a result, many experience stress and poor health that can compromise stroke survivor recovery and threaten the sustainability of keeping the stroke survivor at home. We developed the Timing it Right Stroke Family Support Program (TIRSFSP) to guide the timing of delivering specific types of education and support to meet caregivers' evolving needs. The objective of this multi-site randomized controlled trial is to determine if delivering the TIRSFSP across the stroke care continuum improves caregivers' sense of being supported and emotional well-being. Methods/design Our multi-site single-blinded randomized controlled trial will recruit 300 family caregivers of stroke survivors from urban and rural acute care hospitals. After completing a baseline assessment, participants will be randomly allocated to one of three groups: 1) TIRSFSP guided by a stroke support person (health care professional with stroke care experience), delivered in-person during acute care and by telephone for approximately the first six to 12 months post-stroke; 2) caregiver self-directed TIRSFSP with an initial introduction to the program by a stroke support person, or; 3) standard care receiving the educational resource "Let's Talk about Stroke" prepared by the Heart and Stroke Foundation. Participants will complete three follow-up quantitative assessments 3, 6, and 12-months post-stroke. These include assessments of depression, social support, psychological well-being, stroke knowledge, mastery (sense of control over life), caregiving assistance provided, caregiving impact on everyday life, and indicators of stroke severity and disability. Qualitative methods will also be used to obtain information about caregivers' experiences with the education and support received and the impact on caregivers' perception of being supported and emotional well-being. Discussion This research will determine if the TIRSFSP benefits family caregivers by improving their perception of being supported and emotional well-being. If proven effective, it could be recommended as a model of stroke family education and support that meets the Canadian Stroke Best Practice Guideline recommendation for providing timely education and support to families through transitions.

Postprocedural effects of gastrointestinal endoscopy performed as a day case procedure in children : implications for patient and family education

A prospective design that included a survey tool, nursing care records, and telephone interview was used to determine postprocedural effects experienced by children and families following gastrointestinal endoscopy performed as a day procedure. One hundred twenty-one children attending a pediatric gastroenterology unit for endoscopy under general anesthesia participated in the study. Physical symptoms, day care/school attendance, behavioral issues, and economic factors in the 72 hours post procedure were identified. Over half the children (n = 69, 57%) experienced pain in the hospital post procedure. Pain was reported by 73 children (60%) at home on the day of the procedure, by 55 children (45%) on Day 1 post procedure, and by 37 children (31%) on Day 2 post procedure. The throat was the most common site of pain. Nausea or vomiting was experienced by 37 children (31%) at some time following their procedure but was not associated with procedure type, age, or fasting time. Over half the children (n = 53, 51%) who usually attended day care or school did not attend the day following their procedure. Twenty-four parents (40%) who would normally have worked on the day after the procedure did not attend employment. These findings have been used to improve the preprocedural information and discharge management of patients treated in a pediatric gastroenterology ambulatory setting. © The Society of Gastroenterology Nurses & Associates 2007. All Rights Reserved.

Haemodialysis work environment contributors to job satisfaction and stress: A sequential mixed methods study

Background: Haemodialysis nurses form long term relationships with patients in a technologically complex work environment. Previous studies have highlighted that haemodialysis nurses face stressors related to the nature of their work and also their work environments leading to reported high levels of burnout. Using Kanters (1997) Structural Empowerment Theory as a guiding framework, the aim of this study was to explore the factors contributing to satisfaction with the work environment, job satisfaction, job stress and burnout in haemodialysis nurses. Methods: Using a sequential mixed-methods design, the first phase involved an on-line survey comprising demographic and work characteristics, Brisbane Practice Environment Measure (B-PEM), Index of Work Satisfaction(IWS), Nursing Stress Scale (NSS) and the Maslach Burnout Inventory (MBI). The second phase involved conducting eight semi-structured interviews with data thematically analyzed. Results: From the 417 nurses surveyed the majority were female (90.9 %), aged over 41 years of age (74.3 %), and 47.4 % had worked in haemodialysis for more than 10 years. Overall the work environment was perceived positively and there was a moderate level of job satisfaction. However levels of stress and emotional exhaustion (burnout) were high. Two themes, ability to care and feeling successful as a nurse, provided clarity to the level of job satisfaction found in phase 1. While two further themes, patients as quasi-family and intense working teams, explained why working as a haemodialysis nurse was both satisfying and stressful. Conclusions: Nurse managers can use these results to identify issues being experienced by haemodialysis nurses working in the unit they are supervising.

Work Stress and Early Atherosclerosis: Do Genetic Background and Pre-Employment Risk Factors Explain Conflicting Findings?

According to the models conceptualizing work stress, increased risk of health problems arise when high job demands co-occur with low job control (the demand-control model) or the efforts invested by the employee are disproportionately high compared to the rewards received (effort-reward imbalance model). This study examined the association between work stress and early atherosclerosis with particular attention to the role of pre-employment risk factors and genetic background in this association. The subjects were young healthy adults aged 24-39 who were participating in the 21-year follow-up of the ongoing prospective "Cardiovascular Risk in Young Finns" study in 2001-2002. Work stress was evaluated with questionnaires on demand-control model and on effort-reward model. Atherosclerosis was assessed with ultrasound of carotid artery intima-media thickness (IMT). In addition, risk for enhanced atherosclerotic process was assessed by measuring with heart rate variability and heart rate. Pre-employment risk factors, measured at age 12 to 18, included such as body mass index, blood lipids, family history of coronary heart disease, and parental socioeconomic position. Variants of the neuregulin-1 were determined using genomic DNA. The results showed that higher work stress was associated with higher IMT in men. This association was not attenuated by traditional risk factors of atherosclerosis and coronary heart disease or by pre-employment risk factors measured in adolescence. Neuregulin-1 gene moderated the association between work stress and IMT in men. A significant association between work stress and IMT was found only for the T/T genotype of the neuregulin-1 gene but not for other genotypes. Among women an association was found between higher work stress and lower heart rate variability, suggesting higher risk for developing atherosclerosis. These associations could not be explained by demographic characteristics or coronary risk factors. The present findings provide evidence for an association between work stress and atherosclerosis in relatively young population. This association seems to be modified by genetic influences but it does not appear to be confounded by pre-employment adolescent risk factors.

Childhood and adolescent antecedents of work stress and early atherosclerosis

Work stress is after musculoskeletal disorders the second most common work-related health problem in the European Union, affecting 28% of EU employees. Furthermore, a 50% excessive cardiovascular disease risk among employees with work stress is reported. High job demands combined with low job control according to the Job Demands-Job Control model, or high effort combined with low rewards according to Effort-Reward Imbalance model, are likely to produce work stress in the majority of employees. Atherosclerotic wall thickening is a validated marker of an increased risk of cardiovascular disease. This study examined the role of childhood and adolescent factors as antecedents of work stress and early atherosclerosis, and in the relationship between them. The Cardiovascular Risk in Young Finns Study, (the CRYF project) started in 1980 when the participants were at the age of three to 18 years. Follow-ups have been conducted every three years until 1992, after that in 1997 and 2001, and the latest is ongoing in 2008. The participants parents reported their socioeconomic position in 1980 and 1983, and their life satisfaction in 1983. Biological risk factors were measured in 1980 and 2001. Type A behaviour was reported in 1986, 1989 and 2001. In the 2001 follow-up when the participants were aged 24 to 39, work stress was assessed from responses to questionnaires on job demands-job control and effort-reward imbalance, and education. Ultrasound measurement of the carotid intima-media thickness (CIMT) was used to assess atherosclerosis. There were 755, 746, 1014 and 494 participants in studies I-IV, respectively. The results showed that low parental socioeconomic position and parental life dissatisfaction during childhood and adolescence predicted higher levels of job strain 18 years later, and that education mediated the relationship between parental socioeconomic position and job strain. Childhood and adolescent family factors were not related to the effort-reward imbalance. Parental life satisfaction was associated with high rewards at work among the men, and high parental socioeconomic position was associated with high reward among the women. Among the men, the eagerness-energy component of Type A behaviour across different developmental periods predicted increased CIMT. Among the women, hard-driving component of Type A behaviour predicted decreased CIMT. Low leadership characteristic in adolescence and early adulthood was associated with both high job strain and increased CIMT, and attenuated the relationship between job strain and CIMT to non-significance in men. The current findings add to the literature on the relationship between job strain and health literature in adopting a developmental perspective. The results imply that work stress does not completely originate from work. There are childhood and adolescent environmental and dispositional effects on work stress and CIMT several years later, and these partly seem to operate through educational attainment.

Importance of non-conserved distal carboxyl terminal amino acids in two peptidases belonging to the M1 family: Thermoplasma acidophilum Tricorn interacting factor F2 and Escherichia coli Peptidase N

Enzymes belonging to the M1 family play important cellular roles and the key amino acids (aa) in the catalytic domain are conserved. However, C-terminal domain aa are highly variable and demonstrate distinct differences in organization. To address a functional role for the C-terminal domain, progressive deletions were generated in Tricorn interacting factor F2 from Thermoplasma acidophilum (F2) and Peptidase N from Escherichia coli (PepN). Catalytic activity was partially reduced in PepN lacking 4 C-terminal residues (PepNΔC4) whereas it was greatly reduced in F2 lacking 10 C-terminal residues (F2ΔC10) or PepN lacking eleven C-terminal residues (PepNΔC11). Notably, expression of PepNΔC4, but not PepNΔC11, in E. coliΔpepN increased its ability to resist nutritional and high temperature stress, demonstrating physiological significance. Purified C-terminal deleted proteins demonstrated greater sensitivity to trypsin and bound stronger to 8-amino 1-napthalene sulphonic acid (ANS), revealing greater numbers of surface exposed hydrophobic aa. Also, F2 or PepN containing large aa deletions in the C-termini, but not smaller deletions, were present in high amounts in the insoluble fraction of cell extracts probably due to reduced protein solubility. Modeling studies, using the crystal structure of E. coli PepN, demonstrated increase in hydrophobic surface area and change in accessibility of several aa from buried to exposed upon deletion of C-terminal aa. Together, these studies revealed that non-conserved distal C-terminal aa repress the surface exposure of apolar aa, enhance protein solubility, and catalytic activity in two soluble and distinct members of the M1 family.

Novel CDNF/MANF protein family : Molecular structure, expression and neurotrophic activity

Neurotrophic factors (NTFs) are secreted proteins which promote the survival of neurons, formation and maintenance of neuronal contacts and regulate synaptic plasticity. NTFs are also potential drug candidates for the treatment of neurodegenerative diseases. Parkinson’s disease (PD) is mainly caused by the degeneration of midbrain dopaminergic neurons. Current therapies for PD do not stop the neurodegeneration or repair the affected neurons. Thus, search of novel neurotrophic factors for midbrain dopaminergic neurons, which could also be used as therapeutic proteins, is highly warranted. In the present study, we identified and characterized a novel protein named conserved dopamine neurotrophic factor (CDNF), a homologous protein to mesencephalic astrocyte-derived neurotrophic factor (MANF). Others have shown that MANF supports the survival of embryonic midbrain dopaminergic neurons in vitro, and protects cultured cells against endoplasmic reticulum (ER) stress. CDNF and MANF form a novel evolutionary conserved protein family with characteristic eight conserved cysteine residues in their primary structure. The vertebrates have CDNF and MANF encoding genes, whereas the invertebrates, including Drosophila and Caenorhabditis have a single homologous CDNF/MANF gene. In this study we show that CDNF and MANF are secreted proteins. They are widely expressed in the mammalian brain, including the midbrain and striatum, and in several non-neuronal tissues. We expressed and purified recombinant human CDNF and MANF proteins, and tested the neurotrophic activity of CDNF on midbrain dopaminergic neurons using a 6-hydroxydopamine (6-OHDA) rat model of PD. In this model, a single intrastriatal injection of CDNF protected midbrain dopaminergic neurons and striatal dopaminergic fibers from the 6-OHDA toxicity. Importantly, an intrastriatal injection of CDNF also restored the functional activity of the nigrostriatal dopaminergic system when given after the striatal 6-OHDA lesion. Thus, our study shows that CDNF is a potential novel therapeutic protein for the treatment of PD. In order to elucidate the molecular mechanisms of CDNF and MANF activity, we resolved their crystal structure. CDNF and MANF proteins have two domains; an amino (N)-terminal saposin-like domain and a presumably unfolded carboxy (C)-terminal domain. The saposin-like domain, which is formed by five α-helices and stabilized by three intradomain disulphide bridges, may bind to lipids or membranes. The C-terminal domain contains an internal cysteine bridge in a CXXC motif similar to that of thiol/disulphide oxidoreductases and isomerases, and may thus facilitate protein folding in the ER. Our studies suggest that CDNF and MANF are novel potential therapeutic proteins for the treatment of neurodegenerative diseases. Future studies will reveal the neurotrophic and cytoprotective mechanisms of CDNF and MANF in more detail.

Arabidopsis thaliana J-class heat shock proteins: cellular stress sensors

Plants are sessile organisms that have evolved a variety of mechanisms to maintain their cellular homeostasis under stressful environmental conditions. Survival of plants under abiotic stress conditions requires specialized group of heat shock protein machinery, belonging to Hsp70:J-protein family. These heat shock proteins are most ubiquitous types of chaperone machineries involved in diverse cellular processes including protein folding, translocation across cell membranes, and protein degradation. They play a crucial role in maintaining the protein homeostasis by reestablishing functional native conformations under environmental stress conditions, thus providing protection to the cell. J-proteins are co-chaperones of Hsp70 machine, which play a critical role by stimulating Hsp70s ATPase activity, thereby stabilizing its interaction with client proteins. Using genome-wide analysis of Arabidopsis thaliana, here we have outlined identification and systematic classification of J-protein co-chaperones which are key regulators of Hsp70s function. In comparison with Saccharomyces cerevisiae model system, a comprehensive domain structural organization, cellular localization, and functional diversity of A. thaliana J-proteins have also been summarized. Electronic supplementary material The online version of this article (doi:10.1007/s10142-009-0132-0) contains supplementary material, which is available to authorized users.

Stress and developmental responses in Arabidopsis thaliana: regulation through the transcription factor-interacting protein RCD1

Plants constantly face adverse environmental conditions, such as drought or extreme temperatures that threaten their survival. They demonstrate astonishing metabolic flexibility in overcoming these challenges and one of the key responses to stresses is changes in gene expression leading to alterations in cellular functions. This is brought about by an intricate network of transcription factors and associated regulatory proteins. Protein-protein interactions and post-translational modifications are important steps in this control system along with carefully regulated degradation of signaling proteins. This work concentrates on the RADICAL-INDUCED CELL DEATH1 (RCD1) protein which is an important regulator of abiotic stress-related and developmental responses in Arabidopsis thaliana. Plants lacking this protein function display pleiotropic phenotypes including sensitivity to apoplastic reactive oxygen species (ROS) and salt, ultraviolet B (UV-B) and paraquat tolerance, early flowering and senescence. Additionally, the mutant plants overproduce nitric oxide, have alterations in their responses to several plant hormones and perturbations in gene expression profiles. The RCD1 gene is transcriptionally unresponsive to environmental signals and the regulation of the protein function is likely to happen post-translationally. RCD1 belongs to a small protein family and, together with its closest homolog SRO1, contains three distinguishable domains: In the N-terminus, there is a WWE domain followed by a poly(ADP-ribose) polymerase-like domain which, despite sequence conservation, does not seem to be functional. The C-terminus of RCD1 contains a novel domain called RST. It is present in RCD1-like proteins throughout the plant kingdom and is able to mediate physical interactions with multiple transcription factors. In conclusion, RCD1 is a key point of signal integration that links ROS-mediated cues to transcriptional regulation by yet unidentified means, which are likely to include post-translational mechanisms. The identification of RCD1-interacting transcription factors, most of whose functions are still unknown, opens new avenues for studies on plant stress as well as developmental responses.

Characterization of two M17 family members in Escherichia coli, Peptidase A and Peptidase B

Escherichia coil encodes two aminopeptidases belonging to the M17 family: Peptidase A (PepA) and Peptidase B (PepB). To gain insights into their substrate specificities, PepA or PepB were overexpressed in Delta pepN, which shows greatly reduced activity against the majority of amino acid substrates. Overexpression of PepA or PepB increases catalytic activity of several aminopeptidase substrates and partially rescues growth of Delta pepN during nutritional downshift and hightemperature stress. Purified PepA and PepB display broad substratespecificity and Leu, Lys, Met and Gly are preferred substrates. However, distinct differences are observed between these two paralogs: PepA is more stable at high temperature whereas PepB displays broader substrate specificity as it cleaves Asp and insulin B chain peptide. Importantly, this strategy, i.e. overexpression of peptidases in Delta pepN and screening a panel of substrates for cleavage, can be used to rapidly identify peptidases with novel substrate specificities encoded in genomes of different organisms. (C) 2010 Elsevier Inc. All rights reserved.

Catalytic activity of Peptidase N is required for adaptation of Escherichia coli to nutritional downshift and high temperature stress

Peptidase N (PepN), the sole M1 family member in Escherichia coli, displays broad substrate specificity and modulates stress responses: it lowers resistance to sodium salicylate (NaSal)-induced stress but is required during nutritional downshift and high temperature (NDHT) stress. The expression of PepN does not significantly change during different growth phases in LB or NaSal-induced stress; however, PepN amounts are lower during NDHT stress. To gain mechanistic insights on the roles of catalytic activity of PepN in modulating these two stress responses, alanine mutants of PepN replacing E264 (GAMEN motif) and E298 (HEXXH motif) were generated. There are no major structural changes between purified wild type (WT) and mutant proteins, which are catalytically inactive. Importantly, growth profiles of Delta pepN upon expression of WT or mutant proteins demonstrated the importance of catalytic activity during NDHT but not NaSal-induced stress. Further fluorescamine reactivity studies demonstrated that the catalytic activity of PepN is required to generate higher intracellular amounts of free N-terminal amino acids; consequently, the lower growth of Delta pepN during NDHT stress increases with high amounts of casamino acids. Together, this study sheds insights on the expression and functional roles of the catalytic activity of PepN during adaptation to NDHT stress. (C) 2012 Elsevier GmbH. All rights reserved.