Posttraumatic growth and adjustment to spinal cord injury: moderated by posttraumatic depreciation?

Objective: Findings on the relationship of posttraumatic growth (PTG) with adjustment to potentially traumatic events are inconsistent, whereupon posttraumatic depreciation (PTD) has been suggested as a possible moderator. The objective of this study is to investigate the associations between PTG and PTD on one side and life satisfaction and indicators of mental and physical health on the other side in individuals with spinal cord injury (SCI). The primary study aim is to test whether PTD moderates the relationships of PTG and different adjustment indicators. Method: A total of 141 patients administered to one of four Swiss SCI rehabilitation centers completed questionnaires assessing PTG and PTD, different indicators of mental and physical health as well as life satisfaction at discharge from first rehabilitation. Correlational and regression methods were used to examine the research question. Results: PTG and PTD were significantly positively correlated (rs = .47). PTD was significantly associated with lower mental and physical health and lower life satisfaction, with small to large effect sizes. PTD moderated the associations of PTG with symptoms of depression and life satisfaction (β of interaction term = -.18 and .24, respectively). PTG was significantly related to lower levels of symptoms of depression and higher life satisfaction in individuals experiencing moderate to high levels of PTD. In contrast, PTG was not significantly related to these outcomes in individuals with low PTD levels. Conclusion: The neglect of PTD in research partially explains mixed findings on the relationship of PTG and adjustment to potentially traumatic events. Keywords

Attentional and emotional mechanisms of pain processing and their related factors: a structural equations approach

BACKGROUND/OBJECTIVE: It is known that maladaptive attentional and emotional mechanisms of pain processing – as indicated by constructs such as pain hypervigilance, pain-related anxiety and pain catastrophizing – play an important role in the development and maintenance of chronic pain conditions. However, little is known to date about the potential risk factors for these forms of maladaptive processing. The aim of the present study was to shed more light on this issue. A very comprehensive set of predictor variables was examined in healthy pain-free subjects

Untersuchungen zur PDE-Ausstattung unterschiedlicher Zelllinien und Xenograft-Tumoren sowie zum Wirkmechanismus substituierter Pteridine

In der vorliegenden Arbeit wurde an einem kleinen Spektrum humaner Xenograft-Tumoren exemplarisch die cAMP-hydrolysierende PDE-Aktivität untersucht. Dabei konnte gezeigt werden, dass sich Tumoren unterschiedlichen Gewebeursprungs stark in ihrer cAMP-hydrolysierenden PDE-Aktivität unterscheiden können, aber dass auch bei verschiedenen Tumoren des gleichen Gewebes die PDE-Aktivität ebenfalls stark variiert. Gleichzeitig wurden große Unterschiede im prozentualen Anteil an PDE4 gefunden. In nahezu der Hälfte der untersuchten Xenografts stellen Isoenzyme der PDE4-Familie weniger als 50% an der Gesamt-PDE-Aktivität dar. Bei Untersuchungen des großzelligen humanen Lungenxenografts LXFL529, der verglichen mit allen anderen untersuchten Tumoren die höchste PDE-Aktivität aufweist, konnte gezeigt werden, dass dieses Tumorgewebe PDE4D3 zu enthalten scheint, die jedoch sehr leicht proteolytisch gespalten wird. Außerdem wurden kurze Formen des PDE4D-Gens detektiert. Dabei könnte es sich um PDE4D1, PDE4D2 oder die von Eyschen (1999) aus LXFL529-Tumorgewebe isolierte trunkierte PDE4D3 handeln. Möglicherweise wird in LXFL529-Xenograftgewebe auch eine kurze Form einer nicht zur PDE4D-Isoenzymfamilie gehörenden PDE exprimiert. Zur genauen Bestimmung müssen noch weitere Untersuchungen durchgeführt werden. Bislang wurden wirkmechanistische Untersuchungen mit PDE4-Hemmstoffen ausschließlich an Permanent-Zelllinien durchgeführt. Um Aussagen über die Übertragbarkeit der Ergebnisse in vitro auf die in vivo-Situation zu ermöglichen, wurde Tumorgewebe zweier unterschiedlicher Lungentumor-Xenografts, LXFL529 und das humane kleinzellige Lungenkarzinom LXFS650, bezüglich seiner cAMP-hydrolysierenden PDE-Aktivität und dem Gehalt an PDE4 mit den entsprechenden Permanent-Zelllinien verglichen. Dabei wiesen beide Zelllinien eine wesentlich niedrigere PDE-Gesamtaktivität als die entsprechenden soliden Xenograft-Tumoren auf. Der Anteil an PDE4 liegt in LXFL529L-Zellen und soliden Tumor in der gleichen Größenordnung. Auch im Cytosol von LXFS650 (Zelllinie und Tumor) wird der gleiche Prozentsatz PDE4 nachgewiesen, während er im Partikular der Zelllinie deutlich höher liegt im entsprechenden Tumor. Ein wesentlicher Bestandteil dieser Arbeit waren Untersuchungen zum Wirkmechanismus des potenten PDE4-Inhibitors DC-TA-46. Dieser Hemmstoff zeigt große Unterschiede in den IC50-Werten der Hemmung isolierter PDE4 aus LXFL529-Tumorgewebe (0,016 microM) bzw. der Wachstumshemmung von LXFL529L-Zellen (2,3 microM). Im Rahmen dieser Arbeit konnte gezeigt werden, dass die subzelluläre Verteilung des Hemmstoffs vermutlich eine wesentliche Rolle spielt. Die PDE-Aktivität von Proteinpräparationen aus LXFL529L-Zellen wird durch DC-TA-46 mit IC50-Werten von 0,22 microM (Cytosol) und 0,5 microM (Partikular) gehemmt und unterscheidet sich in der Sensitivität damit nicht von Proteinpräparationen aus solidem Tumorgewebe. Inkubiert man jedoch LXFL529L-Zellen mit der Substanz, so erreicht man erst bei Konzentrationen > 10 -6 M eine Hemmung der cytosolischen PDE-Aktivität. Im Partikular der Zellen zeigt sich hingegen durch die Anreicherung von DC-TA-46 in Membranstrukturen eine deutliche Erhöhung der Hemmwirkung im Vergleich zur entsprechenden isolierten Proteinpräparation. Die Hemmung der intrazellulären PDE-Aktivität scheint dabei auch zelltyp-spezifisch zu sein. Analoge Versuche mit LXFS650L-Zellen zeigten eine deutlich höhere Hemmung der cytosolischen PDE im Vergleich zu LXFL529L-Zellen. Dies scheint mit der höheren Sensitivität von LXFS650L-Zellen gegenüber der wachstumshemmenden Wirkung von DC-TA-46 im Sulforhodamin B-Test zu korrelieren. Diese Untersuchungen zeigten, dass die Bestimmung der intrazellulären Hemmwirkung eine wesentliche Messgröße zur Untersuchung potentieller PDE-Hemmstoffe darstellt. Deshalb wurde für die bislang in unserem Arbeitskreis zur Verfügung stehenden Pteridinderivate die Hemmung der intrazellulären PDE untersucht. Fluoreszenzmikroskopische Untersuchungen an LXFL529L-Zellen ergaben keine Anhaltspunkte für Unterschiede in der subzellulären Lokalisation der verschiedenen Derivate. Alle Substanzen scheinen sich ebenso wie DC-TA-46 in Membranstrukturen in der perinuklearen Region anzureichern. Die Derivate unterscheiden sich jedoch deutlich in ihrer Hemmung. Durch Variation der Substituenten in 4- und 7-Position bzw. an 6-Position konnte am ehesten eine gute PDE-Hemmung erreicht werden. Zwei an 7-Position substituierte Derivate mit basischem Stickstoff ohne H-Donorfunktion zeigten sogar eine bessere Inhibition der zellulären PDE als DC-TA-46. Durch Variationen der Substituenten in 2-Position des Grundgerüsts kann keine bzw. nur geringe Hemmung zellulärer PDE erreicht werden. Die meisten Veränderungen an 4 -Position konnten keine PDE-Hemmung erzielen. Für die Hemmung zellulärer PDE scheint also ein größerer Rest an 6-Position als Wasserstoff wichtig zu sein bzw. eine Wasserstoffdonorfunktion des basischen Stickstoffs in 4 -Position. Lediglich eine an 4 -Position mit einem Acetylrest substituierte Verbindung war in LXFL529L-Zellen ein potenter PDE-Hemmstoff, nicht jedoch am isolierten Enzym, was auf die Freisetzung der Leitsubstanz DC-TA-46 durch metabolische Prozesse in der Zelle zurückzuführen sein kann. Deshalb sollte bei zukünftigen biologischen Testungen nicht nur am isolierten Enzym, sondern auch in Zellen getestet werden sollte, da nur so pharmakologische Prozesse einbezogen werden. In vitro führt die Behandlung von Tumorzellen mit DC-TA-46 zu einem Zellzyklusarrest in der G1-Phase des und zur Induktion von Apoptose [Wagner, 1998; Marko et al., 1998]. Im Rahmen dieser Arbeit konnte gezeigt werden, dass dieser Zellzyklus-Arrest nicht durch die Wirkung des Pteridinderivats auf die Cyclin-abhängigen Kinase-Inhibitoren p21 cip1 und p27 kip1 zustande kommt. Der cAMP-Gehalt von Zellen kann während des Zellzyklus periodischen Schwankungen unterliegen [Millis et al., 1974]. In LXFL529L-Zellen konnte eine positive Korrelation zwischen der PDE-Aktivität im Cytosol und dem Anteil der Zellen in der G0/G1-Phase des Zellzyklus detektiert werden. Im Partikular hingegen ist ein deutlicher Zusammenhang zwischen der PDE-Aktivität und des Gehalts von G2/M-Phase-Zellen bzw. eine negative Korrelation zwischen partikulärer PDE-Aktivität und dem Anteil der G1-Phase-Zellen zu sehen. Da DC-TA-46 aufgrund seiner subzellulären Lokalisation hauptsächlich im Partikular wirksam ist, scheint v.a. die Hemmung der partikulären Isoenzyme für den G1-Arrest wesentlich zu sein. Im Rahmen dieser Arbeit konnte nun umgekehrt gezeigt werden, dass in LXFL529L-Zellen in der G1-Phase eine geringe partikuläre PDE-Aktivität vorliegt

Discovery of the cancer stem cell related determinants of radioresistance

AbstractTumors are known to be heterogeneous containing a dynamic mixture of phenotypically and functionally different tumor cells. The two concepts attempting to explain the origin of intratumor heterogeneity are the cancer stem cell hypothesis and the clonal evolution model. The stochastic model argues that tumors are biologically homogenous and all cancer cells within the tumor have equal ability to propagate the tumor growth depending on continuing mutations and selective pressure. By contrast, the stem cells model suggests that cancer heterogeneity is due to the hierarchy that originates from a small population of cancer stem cells (CSCs) which are biologically distinct from the bulk tumor and possesses self-renewal, tumorigenic and multilineage potential. Although these two hypotheses have been discussed for a long time as mutually exclusive explanations of tumor heterogeneity, they are easily reconciled serving as a driving force of cancer evolution and diversity. Recent discovery of the cancer cell plasticity and heterogeneity makes the CSC population a moving target that could be hard to track and eradicate. Understanding the signaling mechanisms regulating CSCs during the course of cancer treatment can be indispensable for the optimization of current treatment strategies

From dementia mindsets to emotions and behaviors:Predicting person-centered care in care professionals

Background and Objective: High-quality care standards for dementia care are increasingly based on person-centered care principles. To better understand facilitating factors of person-centered care this research focuses on individual characteristics of care professionals. Applying mindset theory to dementia care, we examined dementia mindsets (viewing dementia symptoms as either malleable or fixed) in care professionals. We tested whether there is a positive relationship between a malleable dementia mindset and person-centered care as well as a negative relationship between a fixed dementia mindset and person-centered care. Moreover, we examined whether care professionals’ emotional responses in care situations help explain associations between dementia mindsets and person-centered care. Research Design and Method: In two cross-sectional studies, care professionals of long-term care facilities (total N = 370) completed a measure of dementia mindsets and reported their emotional and behavioral responses to five care scenarios. Regression and mediation analyses were performed. Findings: The tested hypotheses were partially supported. A fixed dementia mindset predicted reported person-centered care negatively, while a malleable dementia mindset did not. Mediation analyses suggest that reduced negative emotions may underlie the association between a malleable mindset and reported person-centered care, while reduced positive emotions in care situations may underlie the association of a fixed mindset and reported person-centered care. Study 2 partially replicated these findings. A fixed mindset and positive emotional responses were the most robust predictors of reported person-centered care. Discussion and Implications: This study extends knowledge on facilitators (positive emotional responses to care situations) and barriers (fixed dementia mindset) to person-centered care in care professionals working with persons with dementia. We discuss how dementia mindsets and emotional responses to care situations may be a fruitful target for trainings for care professionals

Dementia as fixed or malleable:Development and validation of the dementia mindset scale

Background and Objectives Care professionals differ in how they experience and respond to dementia caregiving. To explain such differences, we developed a new measure: the Dementia Mindset Scale. This scale captures the extent to which care professionals view dementia as stable and fixed (akin to the biomedical perspective) or as flexible and malleable (akin to the person-centered approach). Research Design and Methods We conducted four studies to develop the scale. We tested items for comprehensibility, assessed the scale’s factorial structure and psychometric properties, and investigated its predictive validity for care professionals’ well-being. Results A new scale with a two-factor structure—distinguishing a malleable dementia mindset from a fixed dementia mindset—was developed. Results showed good convergent and divergent validity. Moreover, the dementia mindsets predicted aspects of job-related well-being in care professionals. Discussion and Implications The scale allows for the assessment of individual differences in how care professionals see dementia. This insight can be used to improve interventions aimed at enhancing care professionals’ well-being and quality of care

Postoperative Anaemia Might Be a Risk Factor for Postoperative Delirium and Prolonged Hospital Stay: A Secondary Analysis of a Prospective Cohort Study

Background: Postoperative anaemia is a frequent surgical complication and in contrast to preoperative anaemia has not been validated in relation to mortality, morbidity and its associated health economic effect. Postoperative anaemia can predispose postoperative delirium through impairment of cerebral oxygenation. The aim of this secondary analysis is to investigate the association of postoperative anaemia in accordance with the sex specific World Health Organization definition of anaemia to postoperative delirium and its impact on the duration of hospital stay. Methods: A secondary analysis of the prospective multicentric observational CESARO-study was conducted. 800 adult patients undergoing elective surgery were enrolled from various operative disciplines across seven hospitals ranging from university hospitals, district general hospitals to specialist clinics of minimally invasive surgery in Germany. Patients were classified as anaemic according to the World Health Organization parameters, setting the haemoglobin level cut off below 12g/dl for females and below 13g/dl for males. Focus of the investigation were patients with acute anaemia. Patients with present preoperative anaemia or missing haemoglobin measurement were excluded from the sample set. Delirium screening was established postoperatively for at least 24 hours and up to three days, applying the validated Nursing Delirium Screening Scale. Results: The initial sample set contained 800 patients of which 183 were suitable for analysis in the study. Ninety out of 183 (49.2%) suffered from postoperative anaemia. Ten out of 93 (10.9%) patients without postoperative anaemia developed a postoperative delirium. In the group with postoperative anaemia, 28 (38.4%) out of 90 patients suffered from postoperative delirium (odds ratio 3.949, 95% confidence interval, (1.358-11.480)) after adjustment for NYHA-stadium, severity of surgery, cutting/suture time, duration of anaesthesia, transfusion of packed red cells and sedation status with Richmond Agitation Scale after surgery. Additionally, patients who suffered from postoperative anaemia showed a significantly longer duration of hospitalisation (7.75 vs. 12.42 days, odds ratio = 1.186, 95% confidence interval, 1.083-1.299, after adjustments). Conclusion: The study results reveal that postoperative anaemia is not only a frequent postsurgical complication with an incidence probability of almost 50%, but could also be associated with a postoperative delirium and a prolonged hospitalisation

Promoting Students’ Health at University: Key Stakeholders, Cooperation, and Network Development

Background: Cooperation among university units is considered a cornerstone for the promotion of students\u27 health. The underlying mechanisms of health-promoting networks at universities have rarely been examined so far. Shedding light on partnerships is generally limited to the naming of allied actors in a network. Objectives and Methods: In this study, we used network analysis intending to visualize and describe the positions and characteristics of the network actors, and examine organizational relationships to determine the characteristics of the complete network. Results: The network analysis at hand provides in-depth insights into university structures promoting students\u27 health comprising 33 organizational units and hundreds of ties. Both cooperation and communication network show a flat, non-hierarchical structure, which is reflected by its low centralization indices (39–43%) and short average distances (1.43–1.47) with low standard deviations (0.499–0.507), small diameter (3), and the non-existence of subgroups. Density lies between 0.53 and 0.57. According to the respondents, the University Sports Center is considered the most important actor in the context of students\u27 health. Presidium and Institute of Sport and Sports Science play an integral role in terms of network functionality. Conclusion: In the health-promoting network, numerous opportunities for further integration and interaction of actors exist. Indications for transferring results to other universities are discussed. Network analysis enables universities to profoundly analyze their health-promoting structures, which is the basis for sustained network governance and development

Night-time activity forecast by season and weather in a longitudinal design:natural light effects on three years' rest-activity cycles in nursing home residents with dementia

Backround: Night-time agitation is a frequent symptom of dementia. It often causes nursing home admission and has been linked to circadian rhythm disturbances. A positive influence of light interventions on night-time agitation was shown in several studies. The aim of our study was to investigate whether there is a long-term association between regional weather data (as indicator for daylight availability) and 24-hour variations of motor activity. Methods: Motor activity of 20 elderly nursing home residents living with dementia was analyzed using recordings of continuously worn wrist activity monitors over a three-year period. The average recording duration was 479 206 days per participant (mean SD). Regional cloud amount and day length data from the local weather station (latitude: 52 degrees 56N) were included in the analysis to investigate their effects on several activity variables. Results: Nocturnal rest, here defined as the five consecutive hours with the least motor activity during 24 hours (L5), was the most predictable activity variable per participant. There was a significant interaction of night-time activity with day length and cloud amount (F-1,F-1174 = 4.39; p = 0.036). Night-time activity was higher on cloudy short days than on clear short days (p = 0.007), and it was also higher on cloudy short days than on cloudy long days (p = 0.032). Conclusions: The need for sufficient zeitgeber (time cue) strength during winter time, especially when days are short and skies are cloudy, is crucial for elderly people living with dementia. Activity forecast by season and weather might be a valuable approach to anticipate adequately complementary use of electrical light and thereby foster lower night-time activity