Differentiation of neural stem cells in three-dimensional growth factor-immobilized chitosan hydrogel scaffolds

The adult central nervous system (CNS) contains adult neural stem/progenitor cells (NSPCs) that possess the ability to differentiate into the primary cell types found in the CNS and to regenerate lost or damaged tissue. The ability to specifically and spatially control differentiation is vital to enable cell-based CNS regenerative strategies. Here we describe the development of a protein-biomaterial system that allows rapid, stable and homogenous linking of a growth factor to a photocrosslinkable material. A bioactive recombinant fusion protein incorporating pro-neural rat interferon-γ (rIFN-γ) and the AviTag for biotinylation was successfully expressed in Escherichia coli and purified. The photocrosslinkable biopolymer, methacrylamide chitosan (MAC), was thiolated, allowing conjugation of maleimide-strepatavidin via Michael-type addition. We demonstrated that biotin-rIFN-γ binds specifically to MAC-streptavidin in stoichiometric yields at 100 and 200 ng/mL in photocrosslinked hydrogels. For cell studies, NSPCs were photo-encapsulated in 100 ng/mL biotin-rIFN-γ immobilized MAC based scaffolds and compared to similar NSPC-seeded scaffolds combining 100 ng/mL soluble biotin-rIFN-γ vs. no growth factor. Cells were cultured for 8 days after which differentiation was assayed using immunohistochemistry for lineage specific markers. Quantification showed that immobilized biotin-rIFN-γ promoted neuronal differentiation (72.8 ± 16.0%) similar to soluble biotin-rIFN-γ (71.8 ± 13.2%). The percentage of nestin-positive (stem/progenitor) cells as well as RIP-positive (oligodendrocyte) cells were significantly higher in scaffolds with soluble vs. immobilized biotin-rIFN-γ suggesting that 3-D immobilization results in a more committed lineage specification.     

The risk of postpartum hemorrhage in women using high dose of low-molecular-weight heparins during pregnancy

Background

Low-molecular-weight heparins (LMWH) are the most commonly used anticoagulant during pregnancy for prevention or treatment of VTE. However, the size of the associated risk of postpartum haemorrhage (PPH) is unknown.

Objective

To assess the bleeding risk of high dose LMWH, also in relation to time between last dose LMWH and delivery.

Material and methods

From 1999 to 2009, we followed 88 pregnant women who were started on therapeutic anticoagulation. Controls were pregnant women without LMWH, matched 1:4 for parity, mode of delivery, age, gestational age and delivery date. PPH was defined as > 500 ml blood loss for vaginal delivery (severe PPH in vaginal delivery as > 1000 ml) and > 1000 ml for cesarean section (CS). Women were divided into subgroups by the interval between last dose of anticoagulation and delivery (< 12, 12-24 hrs, > 24 hrs).

Results

Risk of PPH after vaginal delivery was 30% and 18% for LMWH-users and non-users, respectively (OR 1.9, 95%CI 1.1-3.5). Risk of severe PPH after vaginal delivery was not different (5.6 vs 5.0%; OR 1.1; 0.4-3.6). Risk of PPH after CS was 12% in LMWH-users and 4% in non-users (OR 2.9; 0.5-19.4). Both events of LMWH-users occurred after emergency CS. The risk of PPH associated with delivery within 24 hours after last dose of LMWH was 1.2 fold higher (95%CI 0.4-3.6) compared to a larger interval.

Conclusion

High dose LMWH carries an increased risk of more than 500 mL blood loss after vaginal delivery. However, this results not in more clinical relevant severe PPHs. The interval between last dose of LMWH and delivery does not influence the risk of PPH.     

Brain natriuretic peptide and acute hypobaric hypoxia in humans

In animal models, the secretion of the cardiac hormone, brain natriuretic peptide (BNP), and its closely related peptide, atrial natriuretic peptide (ANP), are stimulated by acute hypoxia. There is extensive human evidence for a rise in ANP under acute hypoxic conditions but very little evidence regarding the BNP response to acute hypoxia in humans. We therefore subjected seven healthy subjects to an acute hypobaric hypoxic stimulus to examine if BNP secretion increases rapidly. Significant hypoxaemia (mean nadir oxygen saturation 62.3%) was induced but no significant rise in BNP occurred. This suggests that either such acute hypoxaemia is well tolerated by the healthy human heart or it is not a stimulus for BNP secretion.     

A review of the role of alcohol in the pathogenesis of oral cancer and the link between alcohol-containing mouthrinses and oral cancer

This article will review the most recent literature on the effects of alcohol on the oral mucosa, and the possible mechanisms by which alcohol is thought to act as a carcinogen. The article will also consider the possible link between alcohol-containing mouthrinses and oral cancer. The authors recommend that the use of alcohol-containing mouthrinses in high-risk populations should be restricted, pending the outcome of further research.     

Dance is the new metal: adolescent music preferences and substance use across Europe

This study examined relationships between music preferences and substance use (tobacco, alcohol, cannabis) among 18,103 fifteen-year-olds from 10 European countries. In 2005-2006, across Europe, preferences for mainstream Pop (pop chart music) and Highbrow (classical music and jazz) were negatively associated with substance use, while preferences for Dance (house/trance and techno/hardhouse) were associated positively with substance use. In three countries, links were identified between liking Rock (rock, heavy metal punk/hardcore, and gothic) and substance use; associations between Urban (hip-hop and R&B) and substance use were mixed. No substantial gender differences emerged in these patterns, and controlling for relevant covariates did not attenuate the predictive value of substance use. The findings are consistent with the conclusion that music is a robust marker of adolescent substance use.     

Benefits of a hospital-based peer intervention program for violently injured youth

BACKGROUND: Exposure to violence predisposes youths to future violent behavior. Breaking the cycle of violence in inner cities is the primary objective of hospital-based violence intervention and prevention programs. An evaluation was undertaken to determine if a hospital-based, peer intervention program, "Caught in the Crossfire," reduces the risk of criminal justice involvement, decreases hospitalizations from traumatic reinjury, diminishes death from intentional violent trauma, and is cost effective. STUDY DESIGN: We designed a retrospective cohort study conducted between January 1998 and June 2003 at a university-based urban trauma center. The duration of followup was 18 months. Patients were 12 to 20 years of age and were hospitalized for intentional violent trauma. The "enrolled" group had a minimum of five interactions with an intervention specialist. The control group was selected from the hospital database by matching age, gender, race or ethnicity, type of injury, and year of admission. All patients came from socioeconomically disadvantaged areas. RESULTS: The total sample size was 154 patients. Participation in the hospital-based peer intervention program lowered the risk of criminal justice involvement (relative risk=0.67; 95% CI, 0.45, 0.99; p=0.04). There was no effect on risks of reinjury and death. Subsequent violent criminal behavior was reduced by 7% (p=0.15). Logistic regression analysis showed age had a confounding effect on the association between program participation and criminal justice involvement (relative risk=0.71; p=0.043). When compared with juvenile detention center costs, the total cost reduction derived from the intervention program annually was $750,000 to $1.5 million. CONCLUSIONS: This hospital-based peer intervention program reduces the risk of criminal justice system involvement, is more effective with younger patients, and is cost effective. Any effect on reinjury and death will require a larger sample size and longer followup.     

Serotonergic mechanisms in addiction-related memories

Drug-associated memories are a hallmark of addiction and a contributing factor in the continued use and relapse to drugs of abuse. Repeated association of drugs of abuse with conditioned stimuli leads to long-lasting behavioral responses that reflect reward-controlled learning and participate in the establishment of addiction. A greater understanding of the mechanisms underlying the formation and retrieval of drug-associated memories may shed light on potential therapeutic approaches to effectively intervene with drug use-associated memory. There is evidence to support the involvement of serotonin (5-HT) neurotransmission in learning and memory formation through the families of the 5-HT(1) receptor (5-HT(1)R) and 5-HT(2)R which have also been shown to play a modulatory role in the behavioral effects induced by many psychostimulants. While there is a paucity of studies examining the effects of selective 5-HT(1A)R ligands, the available dataset suggests that 5-HT(1B)R agonists may inhibit retrieval of cocaine-associated memories. The 5-HT(2A)R and 5-HT(2C)R appear to be integral in the strong conditioned associations made between cocaine and environmental cues with 5-HT(2A)R antagonists and 5-HT(2C)R agonists possessing potency in blocking retrieval of cocaine-associated memories following cocaine self-administration procedures. The complex anatomical connectivity between 5-HT neurons and other neuronal phenotypes in limbic-corticostriatal brain structures, the heterogeneity of 5-HT receptors (5-HT(X)R) and the conflicting results of behavioral experiments which employ non-specific 5-HT(X)R ligands contribute to the complexity of interpreting the involvement of 5-HT systems in addictive-related memory processes. This review briefly traces the history of 5-HT involvement in retrieval of drug-cue associations and future targets of serotonergic manipulation that may reduce the impact that drug cues have on addictive behavior and relapse.     

The role of performance feedback in the self-assessment of competence: a research study with nursing clinicians

Performance feedback has the potential to contribute to a nurse's self-awareness and, in turn, their ability to self-assess their level of competence. Because a declaration of self-assessment of competence is a current requirement for continuing nursing registration within South Australia, Queensland and Tasmania, the search to identify sources and processes that may assist nurses to self-assess their performance is potentially of benefit to the profession. This paper is based on one aspect of a PhD study exploring the utility of performance feedback primarily from a nursing clinicians' perspective. Focus group interviews were conducted with hospital-based nursing clinicians and the data were analysed using a process of thematic analysis. Findings highlighted that nursing clinicians frequently engaged in a process of performance self-monitoring that was a balance between feeling competent and feeling uncertain in relation to their own level of clinical competence. On a daily basis, nursing clinicians held an assumption of competence to practise that was based on their ability to act in a situation, receiving positive feedback from others and in the absence of evidence to the contrary. At times feelings of doubt or uncertainty intervened especially in situations that were unfamiliar or challenging or when receiving feedback from others that questioned their own perceptions of competence. The findings of the study provide support for the types of self-monitoring processes that serve to enhance both the relevance of feedback for nurses and the quality of evaluative data regarding ongoing competence.