Hydroxyapatite nanoparticle injectable hydrogel scaffold to support osteogenic differentiation of human mesenchymal stem cells.

Bone loss associated with degenerative disease and trauma is a clinical problem increasing with the aging population. Thus, effective bone augmentation strategies are required; however, many have the disadvantages that they require invasive surgery and often the addition of expensive growth factors to induce osteoblast differentiation. Here, we investigated a LaponiteÒ crosslinked, pNIPAM-DMAc copolymer (L-pNIPAM-co-DMAc) hydrogel with hydroxyapatite nanoparticles (HAPna), which can be maintained as a liquid ex vivo, injected via narrow-gauge needle into affected bone, followed by in situ gelation to deliver and induce osteogenic differentiation of human mesenchymal stem cells (hMSC). L-pNIPAM-co-DMAc hydrogels were synthesised and HAPna added post polymerisation. Commercial hMSCs from one donor (Lonza) were incorporated in liquid hydrogel, the mixture solidified and cultured for up to 6 weeks. Viability of hMSCs was maintained within hydrogel constructs containing 0.5 mg/mL HAPna. SEM analysis demonstrated matrix deposition in cellular hydrogels which were absent in acellular controls. A significant increase in storage modulus (G') was observed in cellular hydrogels with 0.5 mg/mL HAPna. Semi-quantitative immunohistochemistry and histological analysis demonstrated that bone differentiation markers and collagen deposition was induced within 48 h, with increased calcium deposition with time. The thermally triggered hydrogel system, described here, was sufficient without the need of additional growth factors or osteogenic media to induce osteogenic differentiation of commercial hMSCs. Preliminary data presented here will be expanded on multiple patient samples to ensure differentiation is seen in these samples. This system could potentially reduce treatment costs and simplify the treatment strategy for orthopaedic repair and regeneration.

A retrospective evaluation of the impact of total smoking cessation on psychiatric inpatients taking clozapine.

OBJECTIVE: To investigate the effect of a complete smoking ban on a group of psychiatric inpatients maintained on the antipsychotic medication clozapine. METHOD: Retrospective data on clozapine dose and plasma levels were collected from a three month period before and a six month period after the introduction of the smoking ban. RESULTS: Before the ban only 4.2% of patients who smoked had a plasma clozapine level > or =1000 microg/l but after the ban this increased to 41.7% of the sample within the six month period following the ban despite dose reductions. CONCLUSION: Abrupt cessation of smoking is associated with a potentially serious risk of toxicity in patients taking clozapine. Plasma clozapine levels must be monitored closely and adjustments made in dosage, if necessary, for at least six months after cessation.

A stochastic mathematical model of the within-herd transmission dynamics of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): fade-out and persistence.

A stochastic, mathematical model of a farrow-finish pig herd was developed and used to investigate the within-herd transmission dynamics of PRRSV, and to examine patterns of on-farm persistence and fade-out. The model was structured to represent the management of a typical European pig herd. Three parameters determining the natural history of infection were derived from the literature. Transmission parameters were chosen using PRRSV antibody data from a cross-sectional study of 103 pig herds (Evans et al., 2008). The seroprevalence by age was generated from the model at 21-day intervals and was compared to the cross-sectional field data using log-likelihood, accounting for the accuracy of the ELISA test used. The model was run for various isolation practices of purchased gilts, contact structure, herd size and the frequency of re-introduction of infectious gilts. The time-dependent log-likelihood patterns varied between herds in a similar way to patterns observed from serological values from the 103 farms. Essentially they indicated two patterns of seroprevalence: herds in which PRRSV was stably persistent, and herds in which PRRSV was unstable, either recently introduced or recently faded-out. With a herd size of 327 sows with identical management, fade-out of virus occurred within 4 weeks in 21.9% of simulations. Without isolation of gilts from sows, fade-out within 250 days decreased from 81.6% to 14.3% and for herd sizes of 75, 150, 300 and 600, the probability of persistence of virus for >1200 days was 4%, 13.4%, 20.4% and 18.2%, respectively. Introduction of virus at a rate of approximately 0.37 times per year resulted in virus persisting for >1200 days in 32.4% of simulations, compared with 17.6% for no re-introduction. Fade-out of virus was most likely to occur within breeding females before virus reached young stock. Persistence was more likely once PRRSV was present in piglets which in turn infected rearing-pigs. The probability of persistence was higher with increased herd size, increased contact between different age groups and increased re-introduction of infectious gilts. The ability of the model to capture the variability in cross-sectional, age-related serological patterns suggests that the processes of re-introduction, persistence and fade-out of PRRSV play critical roles in PRRSV epidemiology. The potential importance to pig production and transmission of virus between herds is discussed.

Some causes of failure of crowns, bridges and dentures.

With increasing emphasis being placed on precision in the construction of prostheses the importance of the visco-elastic characteristics of tooth support should be understood. Since the tooth returns to its resting position quite slowly, especially when repeated or sustained forces have been applied, an impression prepared prior to fully recovery will convey erroneous relationships of the tooth with its neighbours to the working model and, eventually, to the prosthesis. Such an error has been identified in young human subjects when inter-dental wedges, gingival retraction cord, and rubber dam are placed. The preparation of conventional alginate impressions in special trays can displace abutment teeth to a clinically significant degree as was recorded for seven partially dentate patients. Simple precautions will circumvent these potential sources of error.