Heparan sulfate mimetics can efficiently mobilize long-term hematopoietic stem cells

Background

Although mobilization of hematopoietic stem cells and hematopoietic progenitor cells can be achieved with a combination of granulocyte colony-stimulating factor and plerixafor (AMD3100), improving approaches for hematopoietic progenitor cell mobilization is clinically important.

Design and Methods

Heparan sulfate proteoglycans are ubiquitous macromolecules associated with the extracellular matrix that regulates biology of hematopoietic stem cells. We studied the effects of a new family of synthetic oligosaccharides mimicking heparan sulfate on hematopoietic stem cell mobilization. These oligosaccharides were administered intravenously alone or in combination with granulocyte colony-stimulating factor and/or AMD3100 in mice. Mobilized hematopoietic cells were counted and phenotyped at different times and the ability of mobilized hematopoietic stem cells to reconstitute long-term hematopoiesis was determined by competitive transplantation into syngenic lethally irradiated mice followed by secondary transplantation.

Results

Mimetics of heparan sulfate induced rapid mobilization of B-lymphocytes, T-lymphocytes, hematopoietic stem cells and hematopoietic progenitor cells. They increased the mobilization of hematopoietic stem cells and hematopoietic progenitor cells more than 3-fold when added to the granulocyte colony-stimulating factor/AMD3100 association. Hematopoietic stem cells mobilized by mimetics of heparan sulfate or by the granulocyte colony-stimulating factor/AMD3100/mimetics association were as effective as hematopoietic stem cells mobilized by the granulocyte colony-stimulating factor/AMD3100 association for primary and secondary hematopoietic reconstitution of lethally irradiated mice.

Conclusions

This new family of mobilizing agents could alone or in combination with granulocyte colony-stimulating factor and/or AMD3100 mobilize a high number of hematopoietic stem cells that were able to maintain long-term hematopoiesis. These results strengthen the role of heparan sulfates in the retention of hematopoietic stem cells in bone marrow and support the use of small glyco-drugs based on heparan sulfate in combination with granulocyte colony-stimulating factor and AMD3100 to improve high stem cell mobilization, particularly in a prospect of use in human therapeutics.     

Self-tuning for job engagement: Ugandan nurses' self-care strategies in coping with work stress

This qualitative study explored self-care among 15 Ugandan nurses with reputations for thriving despite having difficult working conditions. The analysis revealed that in the face of potential threats to the nurses' job engagement, they engaged in ‘self-tuning’, a salutogenic process involving introspection, sensibility and reflection leading to coping in one or several of these ways: sharing of experiences, trusting in God's providence, engaging in other enjoyable activities, letting go, adapting based on experiences, guarding against workplace hazards, preserving quiet time or clearly separating work from personal life. This study supports previous research that self-tuning is a learnable skill, critical in helping nurses cope with work-related adversity; this should be emphasized both during nursing training and on the job.     

Chronic Social Stress in the Community and Associations with Psychological Distress: A Social Psychological Perspective

Chronic social stress is strongly related to psychological distress in vulnerable groups such as the frail elderly and ill people. Little, however, is known about these phenomena in the general population. The validity and reliability of a new brief measure, the Bergen Social Relationships Scale (BSRS), were investigated in a Norwegian county; the prevalence of chronic social stress was measured using the BSRS, and the associations of chronic social stress and social support with three measures of psychological distress were investigated. Respondents with high BSRS scores had experienced longstanding, important interpersonal relationship problems rather than fleeting stressful incidents. Women reported higher levels of chronic social stress, 60% reporting positively on at least one of the six BSRS items, compared with 50% among men. Social support was negatively and significantly associated with various measures of psychological distress. Chronic social stress was positively and significantly associated with psychological distress. These effects were independent of one another. No buffering effect of social support on social stress was observed. The present data support the importance of positive social ties to health, but suggest that social stress is an independent aspect of social environment with regard to health. If social support and social stress have direct and independent effects on mental health, as the present results indicate, intervention on the one will not necessarily modify the other. Intervention programmes may need to consider explicitly both the lighter and the darker sides of social relationships in building environments that support mental health.     

Preferences of AP position of the straight Caucasian facial profile

IntroductionSeveral investigators have compared the perception of profile attractiveness between professional and non-professional people, different groups of clinicians, and different ethnic groups. Our aim was to study preferences for facial protrusion in the lateral view for a straight Class I profile and to study the influence of gender, age, sex preference, and profession.Material and methodsPortrait images of one male and one female model with a Class I occlusal relationship were warped into nine different antero-posterior positions. An internet site was established to reach as many people as possible, and a request was sent by email to participate in a scientific experiment. Finally, 1707 Caucasion assessors could be grouped.ResultsThe preferred male profile is the straight full ante profile. For a feminine facial profile, the straight average and the straight 2/3 ante profiles were perceived as the most attractive. Surgeons tended to give significantly higher scores to attractive (ante) profiles, which correlated strongly with scores of the orthodontists.ConclusionWhenever possible with combined orthodontic/surgery treatment, straight ante profiles should be aimed for.     

An Investigation of Goodman's Addictive Disorder Criteria in Eating Disorders

The aim of this study was to examine how far Goodman's addictive disorder criteria were met by individuals with eating disorders according to subtypes. The study provided a cross‐sectional comparison among three samples of eating disorders [restricting anorexia nervosa (R‐AN), N = 68; purging anorexia nervosa (P‐AN), N = 42; and bulimia nervosa (BN), N = 66], a sample of substance‐related disorders (SRDs, N = 48) and a sample of matched controls (N = 201). Diagnosis of addictive disorder was made following Goodman's criteria. Addictive personality traits were assessed with the Addiction Potential Scale of the Minnesota Multiphasic Personality Inventory—2 and with the Zuckerman's Sensation Seeking Scale. Results showed that individuals with BN met Goodman's addictive disorder criteria in the same proportion as drug‐addicted individuals (65% vs 60%, p = NS). They both showed higher rates than R‐AN individuals (35%; R‐AN versus BN: F = 11.9, p < 0.001 and R‐AN versus SRD: F = 7.16, p < 0.01). Although BN and SRD showed higher rates of addictive disorders compared with P‐AN, differences were not significant. Scores on the Sensation Seeking and on the Addictive Potential scales paralleled the distribution of addictive disorders, with individuals with BN and with P‐AN showing higher levels than individuals with R‐AN. Results showed that a subgroup of individuals with an eating disorder experiences their disorder as an addiction and may deserve specific therapeutic attention. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.