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1.
Psychol Health ; : 1-16, 2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37415316

ABSTRACT

OBJECTIVES: Haemodialysis extends life for people with end-stage kidney disease (ESKD) worldwide, but it imposes significant psychosocial burdens and there is little evidence about successful adjustment. This study aimed to improve understanding of successful psychosocial adjustment to in-centre haemodialysis (ICHD; dialysis in a hospital or satellite unit). METHODS: Individual semi-structured interviews were conducted with a purposive sample of 18 people with ESKD who had all received in-centre haemodialysis in the UK for at least 90 days in the last two years. An inductive thematic analysis was employed to identify themes from the verbatim interview transcripts. RESULTS: There were four themes: 1) reaching a state of acceptance, which described the importance of accepting the necessity of dialysis; 2) taking an active role in treatment, which described how being actively involved in treatment gave participants greater feelings of autonomy and control; 3) utilising social support networks, which described the benefits of instrumental and emotional support; and 4) building emotional resilience, which described the importance of optimism and positivity. CONCLUSIONS: The themes demonstrated elements of successful adjustment that could be targeted by interventions to promote psychological flexibility and positive adjustment among people receiving in-centre haemodialysis worldwide.

2.
BMC Urol ; 21(1): 157, 2021 Nov 15.
Article in English | MEDLINE | ID: mdl-34775953

ABSTRACT

BACKGROUND: Theory-based intervention materials must be carefully adapted to meet the needs of users with specific physical conditions. Acceptance and Commitment Therapy (ACT) has been adapted successfully for cancer, chronic pain, diabetes, irritable bowel syndrome, multiple sclerosis, and a range of other conditions, but not so far for people receiving renal haemodialysis. This paper presents findings from a study to adapt ACT-based intervention materials specifically for renal dialysis. METHODS: Draft written materials consisting of four stories depicting fictitious individuals who used ACT-related techniques to help overcome different challenges and difficulties related to dialysis were adapted using a systematic patient consultation process. The participants were 18 people aged 19-80 years, with chronic kidney disease and receiving renal dialysis. Individual, semi-structured interviews were conducted to elicit participants' views about how the content of the draft materials should be adapted to make them more realistic and relevant for people receiving renal dialysis and about how the materials should be presented and delivered to people receiving renal dialysis. The interview transcripts were analysed using a qualitative adaptation of the Delphi method in which themes are used as a framework for translating feedback into proposals for modifications. RESULTS: The analysis of patient feedback supported the use of patient stories but suggested they should be presented by video and narrated by real dialysis patients. They also indicated specific adaptations to make the stories more credible and realistic. Participant feedback was translated into proposals for change that were considered along with clinical, ethical and theoretical factors. The outcome was a design for a video-based intervention that separated the stories about individuals from the explanations of the specific ACT techniques and provided greater structure, with material organised into smaller chunks. This intervention is adapted specifically for people receiving renal dialysis while retaining the distinctive theoretical principles of ACT. CONCLUSIONS: The study shows the value of consulting patients in the development of intervention materials and illustrates a process for integrating patient feedback with theoretical, clinical and practical considerations in intervention design.


Subject(s)
Acceptance and Commitment Therapy , Attitude to Health , Patient Education as Topic/methods , Renal Dialysis , Renal Insufficiency, Chronic/therapy , Adult , Aged , Aged, 80 and over , Feedback , Female , Humans , Interviews as Topic , Male , Middle Aged
3.
Br J Nurs ; 30(11): 656-659, 2021 Jun 10.
Article in English | MEDLINE | ID: mdl-34109817

ABSTRACT

This article considers the potential development of advanced clinical practitioners (ACPs) and consultant practitioners, beyond the 'expert' status as defined by Pat Benner in 1984. The suggested Derby Model: 7 Levels of Practice Advancement, adapted from Benner's From Novice to Expert, recognises Health Education England's four pillars of advanced practice and how they can be implemented and enhanced within these senior roles, and what that means in a 21st century healthcare system.


Subject(s)
Clinical Competence , Nurse Practitioners , Consultants , Humans
5.
Psychol Trauma ; 12(1): 101-109, 2020 Jan.
Article in English | MEDLINE | ID: mdl-30816771

ABSTRACT

OBJECTIVE: Rumination is important in adjusting to traumatic events. Evidence suggests that deliberate rumination predicts posttraumatic growth (PTG), and mediates the relationship between coping and PTG. This study examined the relationship between rumination and psychological adjustment following pregnancy termination for fetal abnormality (TFA). METHOD: A cross-sectional, online study was conducted with women who had undergone TFA. Women were recruited from a support organization; 161 women completed the Brief COPE, the Perinatal Grief Scale, the Event-Related Rumination Inventory, and the Posttraumatic Growth Inventory. Data were analyzed using regression and mediation analyses. RESULTS: The results show that women engaged in high levels of intrusive and deliberate rumination post-TFA and that intrusive rumination predicted grief. Intrusive and deliberate rumination predicted PTG, although intrusive rumination was a negative predictor of growth. Deliberate rumination mediated the relationship between grief and PTG. It also mediated the path between positive reframing and PTG, and religious coping and PTG, although the mediation effect depended upon the inclusion of the grief variable in the models. CONCLUSIONS: The results confirm the applicability of the PTG model to TFA and support the relevance of rumination to the PTG experience. The results also have clinical implications. Given the positive relationship between deliberate rumination and PTG, promoting interventions that encourage reflective thinking and narrative construction would benefit women post-TFA, particularly those experiencing high levels of distress and/or at risk of complicated grief. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Subject(s)
Abortion, Induced/psychology , Congenital Abnormalities , Emotional Adjustment , Posttraumatic Growth, Psychological , Psychological Trauma/physiopathology , Psychological Trauma/psychology , Rumination, Cognitive/physiology , Adult , Cross-Sectional Studies , Female , Grief , Humans , Pregnancy
6.
Int J MS Care ; 20(5): 231-237, 2018.
Article in English | MEDLINE | ID: mdl-30374253

ABSTRACT

BACKGROUND: Individuals with multiple sclerosis (MS) have balance deficits that result in falls. Balance tests developed for older adults do not discriminate between fallers and nonfallers with MS. The Balance Evaluation Systems Test (BESTest) identifies body systems contributing to imbalance/fall risk. This study evaluated the test-retest reliability and construct validity of the BESTest to assess balance in individuals with MS, compared the diagnostic accuracy of the BESTest and Berg Balance Scale (BBS), and investigated the minimal detectable change of the BESTest in this population. METHODS: Twenty individuals with MS were recruited. Age, onset of disease, and fall history were obtained. The following measures were used: Expanded Disability Status Scale, University of Illinois at Chicago Fear of Falling Measure, BESTest, and BBS. Twelve participants were retested to determine test-retest reliability of the BESTest. RESULTS: The BESTest demonstrated strong test-retest reliability (intraclass correlation coefficient [3,1] = 0.98 [95% CI, 0.91-0.99], P = .01) and was highly correlated with the BBS (r = 0.94, P = .01). The BBS had poor accuracy to identify fallers. Using a score of 81%, the BESTest had moderate sensitivity (0.89) to identify fallers. The standard error of the measurement for the BESTest was 4.16 points, which translates into a minimal detectable change of 9.7% [90% CI] to 11.5% [95% CI]. CONCLUSIONS: The BESTest demonstrates excellent test-retest reliability and diagnostic utility as a measure of functional balance in persons with moderate MS. A change in BESTest score of at least 10% may indicate a true change in balance performance in this population.

7.
BMC Pregnancy Childbirth ; 17(1): 60, 2017 02 08.
Article in English | MEDLINE | ID: mdl-28178933

ABSTRACT

BACKGROUND: Pregnancy termination for fetal abnormality (TFA) may have profound psychological consequences for those involved. Evidence suggests that women's experience of care influences their psychological adjustment to TFA and that they greatly value compassionate healthcare. Caring for women in these circumstances presents challenges for health professionals, which may relate to their understanding of women's experience. This qualitative study examined health professionals' perceptions of women's coping with TFA and assessed to what extent these perceptions are congruent with women's accounts. METHODS: Fifteen semi-structured interviews were carried out with health professionals in three hospitals in England. Data were analysed using thematic analysis and compared with women's accounts of their own coping processes to identify similarities and differences. RESULTS: Health professionals' perceptions of women's coping processes were congruent with women's accounts in identifying the roles of support, acceptance, problem-solving, avoidance, another pregnancy and meaning attribution as key coping strategies. Health professionals regarded coping with TFA as a unique grieving process and were cognisant of women's idiosyncrasies in coping. They also considered their role as information providers as essential in helping women cope with TFA. The findings also indicate that health professionals lacked insight into women's long-term coping processes and the potential for positive growth following TFA, which is consistent with a lack of aftercare following TFA reported by women. CONCLUSIONS: Health professionals' perceptions of women's coping with TFA closely matched women's accounts, suggesting a high level of understanding. However, the lack of insight into women's long-term coping processes has important clinical implications, as research suggests that coping with TFA is a long-term process and that the provision of aftercare is beneficial to women. Together, these findings call for further research into the most appropriate ways to support women post-TFA, with a view to developing a psychological intervention to better support women in the future.


Subject(s)
Abortion, Induced/psychology , Adaptation, Psychological , Attitude of Health Personnel , Empathy , Fetus/abnormalities , Health Personnel/psychology , Adult , England , Female , Grief , Humans , Male , Middle Aged , Perception , Postnatal Care/psychology , Pregnancy , Qualitative Research
8.
Anxiety Stress Coping ; 30(5): 536-550, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28079405

ABSTRACT

BACKGROUND: Research about termination for fetal abnormality (TFA) suggests that it is a traumatic event with potential negative psychological consequences. However, evidence also indicates that following traumatic events individuals may experience growth. Although TFA's negative psychological outcomes are well documented, little is known of the potential for growth following this event. Therefore, the study's objectives were to measure posttraumatic growth (PTG) post-TFA, examine the relationship between PTG, perinatal grief and coping, and determine the predictors of PTG. DESIGN: An online, retrospective survey was conducted with 161 women. METHODS: Eligible participants were women over 18 who had undergone TFA. Participants were recruited from a support organisation. They completed the Brief COPE, Short Perinatal Grief Scale and Posttraumatic Growth Inventory. Data were analysed using regression analyses. RESULTS: Moderate levels of PTG were observed for "relating to others," "personal strengths" and "appreciation of life." "Positive reframing" was a significant predictor of PTG. Despite using mainly "adaptive" coping strategies, women's grief levels were high. CONCLUSIONS: "Adaptive" coping strategies such as, "positive reframing" are relevant to TFA. They may act as protective factors against distress and as foundations for growth, implicating that interventions such as Cognitive Behavioural Therapy, which aim to reframe women's experience, may be beneficial.


Subject(s)
Abortion, Induced/psychology , Adaptation, Psychological , Fetus/abnormalities , Grief , Adult , Female , Humans , Middle Aged , Prenatal Diagnosis/psychology , Psychiatric Status Rating Scales , Young Adult
9.
J Addict Nurs ; 27(3): 160-79, 2016.
Article in English | MEDLINE | ID: mdl-27580190

ABSTRACT

PURPOSE: Opioid overdose deaths have become an escalating epidemic in the United States. To combat this complex issue, naloxone distribution to the public has been initiated in many states as a harm reduction strategy. While supportive legislation develops and community programs expand, research- and policy-focused literature surrounding this timely topic require exploration, compilation, and analysis. The purpose of this systematic review is to identify trends in the current literature, gaps in the findings, nursing implications, and opportunities for further exploration. METHODS: Following a systematic approach, the keywords "naloxone" and "opioid overdose" were used to retrieve articles through the search engines Academic Search Premier, CINAHL Complete, MEDLINE Complete, PubMed, and Psychology and Behavior Sciences Collection. FINDINGS: In the 38 articles selected for the final review, six categories were discussed: global trends, U.S. overdose education programs with naloxone distribution, barriers to public access of naloxone, political opposition and support, financial impact, and recommendations. After reviewing the findings, gaps in the literature were examined, and nursing implications were acknowledged. ORIGINALITY AND VALUE: Although many authors have researched and discussed public naloxone distribution, a comprehensive review of the current evidence is useful and necessary to enhance future research, practice, and policy efforts. By discovering significant gaps in the literature and by recognizing opportunities for nursing practice, this literature review provides valuable input for healthcare professionals, public health officials, policymakers, and laypersons to better understand an ethically, politically, and socially complicated public health initiative.


Subject(s)
Naloxone/administration & dosage , Narcotic Antagonists/administration & dosage , Opioid-Related Disorders/prevention & control , Analgesics, Opioid , Drug Overdose/nursing , Drug Overdose/prevention & control , Humans , Opioid-Related Disorders/nursing , Public Health , United States
10.
PeerJ ; 4: e1575, 2016.
Article in English | MEDLINE | ID: mdl-26793427

ABSTRACT

Background. Osteoporosis is "a pediatric disease with geriatric consequences." Bone morphology and tissue quality co-adapt during ontogeny for sufficient bone stiffness. Altered bone morphology from hypothalamic amenorrhea, a risk factor for low bone mass in women, may affect bone strength later in life. Our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume (BV/TV) at maturity. Methods. Female rats (25 days old) were assigned to a control (C) group (n = 45) that received saline injections (.2 cc) or an experimental group (GnRH-a) (n = 45) that received gonadotropin releasing hormone antagonist injections (.24 mg per dose) for 25 days. Fifteen animals from each group were sacrificed immediately after the injection protocol at Day 50 (C, GnRH-a). The remaining animals recovered for 135 days and a subset of each group was sacrificed at Day 185 ((C-R) (n = 15) and (G-R) (n = 15)). The remaining animals had an ovariectomy surgery (OVX) at 185 days of age and were sacrificed 40 days later (C-OVX) (n = 15) and (G-OVX) (n = 15). After sacrifice femurs were mechanically tested and scanned using micro CT. Serum C-terminal telopeptides (CTX) and insulin-like growth factor 1 (IGF-1) were measured. Two-way ANOVA (2 groups (GnRH-a and Control) X 3 time points (Injection Protocol, Recovery, post-OVX)) was computed. Results. GnRH-a injections suppressed uterine weights (72%) and increased CTX levels by 59%. Bone stiffness was greater in the GnRH-a groups compared to C. Ash content and cortical bone area were similar between groups at all time points. Polar moment of inertia, a measure of bone architecture, was 15% larger in the GnRH-a group and remained larger than C (19%) following recovery. Both the polar moment of inertia and cortical area increased linearly with the increases in body weight. Following the injection protocol, trabecular BV/TV was 31% lower in the GnRH-a group compared to C, a similar deficit in BV/TV was also measured following recovery and post-OVX. The trabecular number and thickness were lower in the GnRH-a group compared to control. Conclusion. These data suggest that following a transient delay in pubertal onset, trabecular bone volume was significantly lower and no restoration of bone volume occurred following recovery or post-OVX surgery. However, cortical bone strength was maintained through architectural adaptations in the cortical bone envelope. An increase in the polar moment of inertia offset increased bone resorption. The current data are the first to suppress trabecular bone during growth, and then add an OVX protocol at maturity. Trabecular bone and cortical bone differed in their response to hypothalamic suppression during development; trabecular bone was more sensitive to the negative effects of hypothalamic suppression.

11.
Circ Res ; 116(10): e81-94, 2015 May 08.
Article in English | MEDLINE | ID: mdl-25801898

ABSTRACT

RATIONALE: Optimization of cell therapy for cardiac repair may require the association of different cell populations with complementary activities. OBJECTIVE: Compare the reparative potential of saphenous vein-derived pericytes (SVPs) with that of cardiac stem cells (CSCs) in a model of myocardial infarction, and investigate whether combined cell transplantation provides further improvements. METHODS AND RESULTS: SVPs and CSCs were isolated from vein leftovers of coronary artery bypass graft surgery and discarded atrial specimens of transplanted hearts, respectively. Single or dual cell therapy (300 000 cells of each type per heart) was tested in infarcted SCID (severe combined immunodeficiency)-Beige mice. SVPs and CSCs alone improved cardiac contractility as assessed by echocardiography at 14 days post myocardial infarction. The effect was maintained, although attenuated at 42 days. At histological level, SVPs and CSCs similarly inhibited infarct size and interstitial fibrosis, SVPs were superior in inducing angiogenesis and CSCs in promoting cardiomyocyte proliferation and recruitment of endogenous stem cells. The combination of cells additively reduced the infarct size and promoted vascular proliferation and arteriogenesis, but did not surpass single therapies with regard to contractility indexes. SVPs and CSCs secrete similar amounts of hepatocyte growth factor, vascular endothelial growth factor, fibroblast growth factor, stem cell factor, and stromal cell-derived factor-1, whereas SVPs release higher quantities of angiopoietins and microRNA-132. Coculture of the 2 cell populations results in competitive as well as enhancing paracrine activities. In particular, the release of stromal cell-derived factor-1 was synergistically augmented along with downregulation of stromal cell-derived factor-1-degrading enzyme dipeptidyl peptidase 4. CONCLUSIONS: Combinatory therapy with SVPs and CSCs may complementarily help the repair of infarcted hearts.


Subject(s)
Myocardial Infarction/surgery , Myocardium/pathology , Myocytes, Cardiac/transplantation , Neovascularization, Physiologic , Pericytes/transplantation , Regeneration , Stem Cell Transplantation , Angiogenic Proteins/metabolism , Animals , Cell Differentiation , Cell Proliferation , Cell Survival , Cells, Cultured , Coculture Techniques , Disease Models, Animal , Fibrosis , Hemodynamics , Humans , Mice, SCID , Myocardial Contraction , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Myocardium/metabolism , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Paracrine Communication , Pericytes/metabolism , Phenotype , Recovery of Function , Saphenous Vein/cytology , Time Factors , Ventricular Remodeling
12.
Reprod Health Matters ; 22(44): 191-201, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25555776

ABSTRACT

Due to technological advances in antenatal diagnosis of fetal abnormalities, more women face the prospect of terminating pregnancies on these grounds. Much existing research focuses on women's psychological adaptation to this event. However, there is a lack of holistic understanding of women's experiences. This article reports a systematic review of qualitative studies into women's experiences of pregnancy termination for fetal abnormality. Eight databases were searched up to April 2014 for peer-reviewed studies, written in English, that reported primary or secondary data, used identifiable and interpretative qualitative methods, and offered a valuable contribution to the synthesis. Altogether, 4,281 records were screened; 14 met the inclusion criteria. The data were synthesised using meta-ethnography. Four themes were identified: a shattered world, losing and regaining control, the role of health professionals and the power of cultures. Pregnancy termination for fetal abnormality can be considered as a traumatic event that women experience as individuals, in their contact with the health professional community, and in the context of their politico-socio-legal environment. The range of emotions and experiences that pregnancy termination for fetal abnormality generates goes beyond the abortion paradigm and encompasses a bereavement model. Coordinated care pathways are needed that enable women to make their own decisions and receive supportive care.


Subject(s)
Abortion, Induced/psychology , Congenital Abnormalities/psychology , Self Concept , Anthropology, Cultural , Bereavement , Decision Making , Empathy , Female , Humans , Pregnancy , Professional-Patient Relations , Stereotyping
13.
Prenat Diagn ; 33(12): 1173-82, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23943597

ABSTRACT

OBJECTIVE: Pregnancy termination for foetal abnormality (TFA) can have significant psychological repercussions, but little is known about the coping strategies involved in dealing with TFA. This study examined the relationships between women's coping strategies and perinatal grief. METHOD: A total of 166 women completed a survey online. Coping and perinatal grief were measured using the Brief COPE and Short Perinatal Grief Scales. Data were analysed through multiple regression analyses. RESULTS: Despite using mostly adaptive coping strategies, women's levels of grief were high and varied according to obstetric and termination variables. Grief was predicted by behavioural disengagement, venting, planning, religion, self-blame, being recently bereaved, being childless at the time of TFA, not having had children/being pregnant since TFA and uncertainty about the decision to terminate the pregnancy. Acceptance and positive reframing negatively predicted grief. CONCLUSION: Identifying women vulnerable to poor psychological adjustment and promoting coping strategies associated with lower levels of grief may be beneficial. This could be addressed through information provision and interventions such as Cognitive Behavioural Therapy or Acceptance and Commitment Therapy.


Subject(s)
Abortion, Induced/psychology , Adaptation, Psychological , Congenital Abnormalities , Grief , Adult , Cross-Sectional Studies , Female , Gestational Age , Humans , Middle Aged , Pregnancy , Surveys and Questionnaires
14.
Br J Educ Psychol ; 83(Pt 3): 452-66, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23822531

ABSTRACT

BACKGROUND: Development of socio-emotional competencies is key to children's successful social interaction at home and at school. AIMS: This study examines the efficacy of a UK primary school-based intervention, the Pyramid project, in strengthening children's socio-emotional competencies. SAMPLE: Participants were 385 children from seven schools in two UK cities. All children were aged 7-8 years and in school Year 3. Children were screened for socio-emotional difficulties through the Strengths and Difficulties Questionnaire (SDQ; Goodman, 1997) and a multi-agency meeting of relevant professionals before being allocated to attend a Pyramid Club intervention (n= 103) or a comparison group (n= 282). METHOD: A 2 × 2 mixed-model design was used: group (intervention group vs. comparison group) × 2 time points (pre- vs. 12 weeks post-intervention) with repeated measures on the time factor to investigate the impact of the Pyramid Year 3 intervention. Teachers completed the SDQ-T4-16 for all children pre- and post-intervention to measure participants' socio-emotional health status. RESULTS: As measured by the two SDQ difficulty sub-scales of Emotional and Peer problems and the SDQ strength sub-scale of Prosocial behaviour, post-intervention improvements in the Pyramid attendee group were of greater magnitude than those of the comparison group. CONCLUSIONS: The Pyramid project intervention improves the socio-emotional health of vulnerable children through promoting positive outcomes as well as reducing socio-emotional deficits. These findings further support the inclusion of a salutogenic approach in promoting children's socio-emotional well-being.


Subject(s)
Achievement , Emotions , Interpersonal Relations , Program Evaluation/methods , Analysis of Variance , Child , Female , Humans , Male , Peer Group , Schools , Surveys and Questionnaires , United Kingdom
15.
Qual Health Res ; 23(7): 924-36, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23558712

ABSTRACT

Pregnancy termination for fetal abnormality (TFA) can have significant psychological consequences. Most previous research has been focused on measuring the psychological outcomes of TFA, and little is known about the coping strategies involved. In this article, we report on women's coping strategies used during and after the procedure. Our account is based on experiences of 27 women who completed an online survey. We analyzed the data using interpretative phenomenological analysis. Coping comprised four structures, consistent across time points: support, acceptance, avoidance, and meaning attribution. Women mostly used adaptive coping strategies but reported inadequacies in aftercare, which challenged their resources. The study's findings indicate the need to provide sensitive, nondirective care rooted in the acknowledgment of the unique nature of TFA. Enabling women to reciprocate for emotional support, promoting adaptive coping strategies, highlighting the potential value of spending time with the baby, and providing long-term support (including during subsequent pregnancies) might promote psychological adjustment to TFA.


Subject(s)
Abortion, Eugenic/psychology , Adaptation, Psychological , Abortion, Eugenic/methods , Adult , Bereavement , Cross-Sectional Studies , Family Characteristics , Female , Gestational Age , Gravidity , Humans , Pregnancy , Retrospective Studies , Self Concept , Social Support , Socioeconomic Factors , United Kingdom
16.
EMBO Mol Med ; 5(4): 626-39, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23505062

ABSTRACT

HDAC inhibitors (HDACi) exert beneficial effects in mdx mice, by promoting endogenous regeneration; however, the cellular determinants of HDACi activity on dystrophic muscles have not been determined. We show that fibroadipogenic progenitors (FAP) influence the regeneration potential of satellite cells during disease progression in mdx mice and mediate HDACi ability to selectively promote regeneration at early stages of disease. FAPs from young mdx mice promote, while FAPs from old mdx mice repress, satellite cell-mediated formation of myotubes. In young mdx mice HDACi inhibited FAP adipogenic potential, while enhancing their ability to promote differentiation of adjacent satellite cells, through upregulation of the soluble factor follistatin. By contrast, FAPs from old mdx mice were resistant to HDACi-mediated inhibition of adipogenesis and constitutively repressed satellite cell-mediated formation of myotubes. We show that transplantation of FAPs from regenerating young muscles restored HDACi ability to increase myofibre size in old mdx mice. These results reveal that FAPs are key cellular determinants of disease progression in mdx mice and mediate a previously unappreciated stage-specific beneficial effect of HDACi in dystrophic muscles.


Subject(s)
Adipogenesis/drug effects , Histone Deacetylase Inhibitors/administration & dosage , Muscles/physiopathology , Muscular Dystrophies/drug therapy , Satellite Cells, Skeletal Muscle/cytology , Stem Cells/cytology , Age Factors , Animals , Cells, Cultured , Humans , Mice , Mice, Inbred C57BL , Mice, Inbred mdx , Mice, Knockout , Mice, SCID , Muscles/drug effects , Muscular Dystrophies/physiopathology , Satellite Cells, Skeletal Muscle/drug effects , Stem Cells/drug effects
17.
Eur Respir J ; 41(6): 1315-23, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23018911

ABSTRACT

A20 is a lipopolysaccharide (LPS)-inducible, cytoplasmic zinc finger protein, which inhibits Toll-like receptor-activated nuclear factor (NF)-κB signalling by deubiquitinating tumour necrosis factor receptor-associated factor (TRAF)-6. The action of A20 is facilitated by complex formation with ring finger protein (RNF)-11, Itch and TAX-1 binding protein-1 (TAX1BP1). This study investigated whether the expression of A20 is altered in the chronically inflamed cystic fibrosis (CF) airway epithelium. Nasal epithelial cells from CF patients (F508del homozygous), non-CF controls and immortalised epithelial cells (16HBE14o- and CFBE41o-) were stimulated with LPS. Cytoplasmic expression of A20 and expression of NF-κB subunits were analysed. Formation of the A20 ubiquitin editing complex was also investigated. In CFBE41o-, peak LPS-induced A20 expression was delayed compared with 16HBE14o- and fell significantly below basal levels 12-24 h after LPS stimulation. This was confirmed in primary CF airway cells. Additionally, a significant inverse relationship between A20 and p65 expression was observed. Inhibitor studies showed that A20 does not undergo proteasomal degradation in CFBE41o-. A20 interacted with TAX1BP1, RNF11 and TRAF6 in 16HBE14o- cells, but these interactions were not observed in CFBE41o-. The expression of A20 is significantly altered in CF, and important interactions with complex members and target proteins are lost, which may contribute to the state of chronic NF-κB-driven inflammation.


Subject(s)
Cystic Fibrosis/metabolism , DNA-Binding Proteins/metabolism , Epithelium/metabolism , Gene Expression Regulation , Intracellular Signaling Peptides and Proteins/metabolism , NF-kappa B/metabolism , Nuclear Proteins/metabolism , Bronchi/cytology , Cell Line , Epithelial Cells/cytology , Epithelial Cells/metabolism , Flow Cytometry , Humans , Inflammation , Interleukin-8/metabolism , Lipopolysaccharides/metabolism , Proteasome Endopeptidase Complex/metabolism , Protein Structure, Tertiary , Signal Transduction , Tumor Necrosis Factor alpha-Induced Protein 3
18.
Circ Res ; 109(8): 894-906, 2011 Sep 30.
Article in English | MEDLINE | ID: mdl-21868695

ABSTRACT

RATIONALE: Pericytes are key regulators of vascular maturation, but their value for cardiac repair remains unknown. OBJECTIVE: We investigated the therapeutic activity and mechanistic targets of saphenous vein-derived pericyte progenitor cells (SVPs) in a mouse myocardial infarction (MI) model. METHODS AND RESULTS: SVPs have a low immunogenic profile and are resistant to hypoxia/starvation (H/S). Transplantation of SVPs into the peri-infarct zone of immunodeficient CD1/Foxn-1(nu/nu) or immunocompetent CD1 mice attenuated left ventricular dilatation and improved ejection fraction compared to vehicle. Moreover, SVPs reduced myocardial scar, cardiomyocyte apoptosis and interstitial fibrosis, improved myocardial blood flow and neovascularization, and attenuated vascular permeability. SVPs secrete vascular endothelial growth factor A, angiopoietin-1, and chemokines and induce an endogenous angiocrine response by the host, through recruitment of vascular endothelial growth factor B expressing monocytes. The association of donor- and recipient-derived stimuli activates the proangiogenic and prosurvival Akt/eNOS/Bcl-2 signaling pathway. Moreover, microRNA-132 (miR-132) was constitutively expressed and secreted by SVPs and remarkably upregulated, together with its transcriptional activator cyclic AMP response element-binding protein, on stimulation by H/S or vascular endothelial growth factor B. We next investigated if SVP-secreted miR-132 acts as a paracrine activator of cardiac healing. In vitro studies showed that SVP conditioned medium stimulates endothelial tube formation and reduces myofibroblast differentiation, through inhibition of Ras-GTPase activating protein and methyl-CpG-binding protein 2, which are validated miR-132 targets. Furthermore, miR-132 inhibition by antimiR-132 decreased SVP capacity to improve contractility, reparative angiogenesis, and interstitial fibrosis in infarcted hearts. CONCLUSION: SVP transplantation produces long-term improvement of cardiac function through a novel paracrine mechanism involving the secretion of miR-132 and inhibition of its target genes.


Subject(s)
Mesenchymal Stem Cell Transplantation/methods , MicroRNAs/biosynthesis , Myocardial Infarction/surgery , Neovascularization, Physiologic/physiology , Pericytes/transplantation , Stem Cells , Animals , Cells, Cultured , Humans , Male , Mice , Mice, Nude , MicroRNAs/metabolism , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Pericytes/metabolism , Rats , Stem Cells/metabolism
19.
J Vet Diagn Invest ; 23(6): 1097-103, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22362788

ABSTRACT

Migration of Parelaphostrongylus spp. has been documented to cause central nervous system damage in a number of aberrant host species but appears to be uncommon in cattle. The current report describes the clinical and laboratory findings, antemortem and definitive diagnosis, and response to treatment of Parelaphostrongylus spp. infection in five 3-7- month-old Limousin calves from 2 farms. All calves had signs of acute (n = 2) and chronic (n = 3) progressive spinal cord dysfunction. Cerebrospinal fluid analysis revealed a marked eosinophilic (acute cases) or lymphocytic (chronic cases) pleocytosis and elevated protein in all calves. A necropsy and histopathologic evaluation was performed on 2 euthanized calves, and histopathology revealed lymphoplasmacytic and eosinophilic meningomyelitis with multiple intradural and intramedullary expansile hyperplastic lymphoid nodules containing germinal centers and nematode fragments. DNA sequencing was performed on nested polymerase chain reaction products amplified with parasite-specific primers obtained from formalin-fixed and frozen spinal cord; PCR products from these 2 calves were 100% identical to Parelaphostrongylus species on DNA sequencing, confirming the diagnosis. Surviving calves rapidly improved following treatment with anthelmintics and corticosteroids. This case series identified Parelaphostrongylus spp. (likely P. tenuis) as a cause of spinal cord disease in calves and highlights the need for vigilance against aberrant parasite migration in calves grazing wet, snail-infested pastures. Cerebrospinal fluid eosinophilia is useful for supporting an antemortem diagnosis of Parelaphostrongylus in calves with acute neurologic disease; however, a lymphocytosis is observed in chronic or treated cases.


Subject(s)
Cattle Diseases/parasitology , Myelitis/veterinary , Nematoda/classification , Nematode Infections/veterinary , Animals , Anthelmintics/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Cattle , Cattle Diseases/drug therapy , Cattle Diseases/pathology , Dexamethasone/therapeutic use , Female , Male , Myelitis/parasitology , Myelitis/pathology , Nematoda/physiology , Nematode Infections/drug therapy , Nematode Infections/parasitology , Nematode Infections/pathology , Spinal Cord/parasitology , Spinal Cord/pathology
20.
J Occup Health Psychol ; 15(3): 223-36, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20604630

ABSTRACT

This paper describes a method for taking a known prevention intervention and modifying it to suit young restaurant workers. Such workers are at high risk for alcohol and other drug (AOD) abuse according to national surveys. While evidence-based programs for AOD prevention exist, they have not been delivered to restaurants. Accordingly, an adaptation methodology was developed by integrating curricula from a previous evidence-based program with research on resilience and input from stakeholders, such as young restaurant workers, their managers, trainers, and subject matter experts. A new curriculum (Team Resilience) maintained fidelity to the original program while incorporating stakeholder insights. At the end of each of three training sessions, participants (n = 124) rated their awareness of AOD risks, help-seeking orientation, and personal resilience. Ratings tended to increase across sessions, showing participants perceived benefits from Team Resilience. Discussion highlights the need for research-to-practice protocols in occupational health psychology.


Subject(s)
Cooperative Behavior , Resilience, Psychological , Restaurants , Adolescent , Adult , Alcoholism/prevention & control , Female , Humans , Male , Occupational Health , Substance-Related Disorders/prevention & control , Surveys and Questionnaires , United States , Workforce , Young Adult
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