The effect of surface chemistry modification of titanium alloy on signalling pathways in human osteoblasts

Establishing and maintaining mature bone at the bone–device interface is critical to the long-term success of prosthesis. Poor cell adhesion to orthopaedic and dental implants results in implant failure. Considerable effort has been devoted to alter the surface characteristics of these biomaterials in order to improve the initial interlocking of the device and skeleton. We investigated the effect of surface chemistry modification of titanium alloy (Ti–6Al–4V) with zinc, magnesium or alkoxide-derived hydroxy carbonate apatite (CHAP) on the regulation of key intracellular signalling proteins in human bone-derived cells (HBDC) cultured on these modified Ti–6Al–4V surfaces. Western blotting demonstrated that modifying Ti–6Al–4V with CHAP or Mg results in modulation of key intracellular signalling proteins. We showed an enhanced activation of Shc, a common point of integration between integrins and the Ras/Mapkinase pathway. Mapkinase pathway was also upregulated, suggesting its role in mediating osteoblastic cell interactions with biomaterials. The signalling pathway involving c-fos (member of the activated protein-1) was also shown to be upregulated in osteoblasts cultured on the Mg and CHAP modified Ti–6Al–4V. Thus surface modification with CHAP or Mg may contribute to successful osteoblast function and differentiation at the skeletal tissue–device interface.     

Genotypic analysis of sequential genital herpes simplex virus type 1 (HSV-1) isolates of patients with recurrent HSV-1 associated genital herpes

Clinical recurrences of Herpes simplex virus type 1 (HSV-1)-associated genital herpes are thought to be caused by reactivation of latent endogenous HSV-1. However, the possibility of reinfection with exogenous HSV-1 cannot be excluded. This study aimed to determine the incidence of genital HSV-1 superinfection in patients by investigating the genotype of sequential HSV-1 isolates obtained from the same anatomical site of patients with clinical recurrences of genital HSV-1 recurrent genital herpes. Sequential genital HSV-1 isolates were genotyped by PCR amplification of the hypervariable regions located within the HSV-1 genes US1 and US12. Whereas the sequential HSV-1 isolates in 11 of the 13 patients studied had the same genotypes, the sequential isolates of 2 patients showed a different genotype. The data suggest that HSV-1-induced recurrent genital herpes can be associated with genital reinfection with an exogenous HSV-1 strain.     

Four phase 1 trials to evaluate the safety and pharmacokinetic profile of single and repeated dosing of SCO‐101 in adult male and female volunteers

SCO‐101 (Endovion) was discontinued 20 years ago as a new drug under development against sickle cell anaemia. Data from the phase 1 studies remained unpublished. New data indicate that SCO‐101 might be efficacious as add‐on therapy in cancer. Thus, we report the results from the four phase 1 trials performed between 2001 and 2002. Adult volunteers received SCO‐101 or placebo in four independent trials. Adverse events were recorded, and SCO‐101 was determined for pharmacokinetic analysis. Ninety‐two volunteers completed the trials. The most remarkable adverse effect was a transient and dose‐dependent increase in unconjugated bilirubin. Plasma SCO‐101 elimination was approximately log linear, with apparent oral clearances of between 315 and 2103 mL/h for single doses, and between 121 and 2433 mL/h at steady state following oral administration. There was a marked decrease in clearance with increasing dose, and for repeated dose versus single dose. T_max was greater, and C_max and AUC_∞ were lower in the fed state compared to the fasted state. Exposure was equivalent in males and females and for African Americans and Caucasians. In conclusion, SCO‐101 appears to be a safe drug with a predictable PK profile. Its efficacy as add‐on to standard anticancer drugs has yet to be defined.     

Web-Based STAR E-Learning Course Increases Empathy and Understanding in Dementia Caregivers: Results from a Randomized Controlled Trial in the Netherlands and the United Kingdom

BackgroundThe doubling of the number of people with dementia in the coming decades coupled with the rapid decline in the working population in our graying society is expected to result in a large decrease in the number of professionals available to provide care to people with dementia. As a result, care will be supplied increasingly by untrained informal caregivers and volunteers. To promote effective care and avoid overburdening of untrained and trained caregivers, they must become properly skilled. To this end, the European Skills Training and Reskilling (STAR) project, which comprised experts from the domains of education, technology, and dementia care from 6 countries (the Netherlands, Sweden, Italy, Malta, Romania, and the United Kingdom), worked together to create and evaluate a multilingual e-learning tool. The STAR training portal provides dementia care training both for informal and formal caregivers.ObjectiveThe objective of the current study was to evaluate the user friendliness, usefulness, and impact of STAR with informal caregivers, volunteers, and professional caregivers.MethodsFor 2 to 4 months, the experimental group had access to the STAR training portal, a Web-based portal consisting of 8 modules, 2 of which had a basic level and 6 additional modules at intermediate and advanced levels. The experimental group also had access to online peer and expert communities for support and information exchange. The control group received free access to STAR after the research had ended. The STAR training portal was evaluated in a randomized controlled trial among informal caregivers and volunteers in addition to professional caregivers (N=142) in the Netherlands and the United Kingdom. Assessments were performed with self-assessed, online, standardized questionnaires at baseline and after 2 to 4 months. Primary outcome measures were user friendliness, usefulness, and impact of STAR on knowledge, attitudes, and approaches of caregivers regarding dementia. Secondary outcome measures were empathy, quality of life, burden, and caregivers’ sense of competence.ResultsSTAR was rated positively by all user groups on both usefulness and user friendliness. Significant effects were found on a person-centered care approach and on the total score on positive attitudes to dementia; both the experimental and the control group increased in score. Regarding empathy, significant improvements were found in the STAR training group on distress, empathic concern, and taking the perspective of the person with dementia. In the experimental group, however, there was a significant reduction in self-reported sense of competence.ConclusionsThe STAR training portal is a useful and user-friendly e-learning method, which has demonstrated its ability to provide significant positive effects on caregiver attitudes and empathy.     

Platelet adhesion to collagen in healthy volunteers is influenced by variation of both alpha(2)beta(1) density and von Willebrand factor

Platelet thrombus formation on collagen is initiated by platelet GPIb interaction with von Willebrand factor (vWF) bound to collagen, followed by firm attachment of the platelet to collagen by the integrin alpha(2)beta(1). Platelet and plasma vWF levels and alpha(2)beta(1) density on the platelet surface are highly variable among normal subjects; however, little is known about the consequences of this variability on platelet adhesion to collagen. A population of 32 normal subjects was studied to evaluate the relation between genetic and phenotypic variations of alpha(2)beta(1) density on the platelet surface, plasma vWF levels, platelet vWF levels, and adenosine diphosphate and adenosine triphosphate concentrations on the one hand and platelet adhesion to collagen under flow on the other hand. Platelet adhesion to collagen types I and III under flow was correlated with plasma levels of vWF (r(2) = 0.45 and 0.42, respectively) and alpha(2)beta(1) density on the platelet surface (r(2) = 0.35 and 0.17, not significant). Platelet adhesion to collagen type IV under flow was significantly correlated with platelet vWF levels (r(2) = 0.34) and alpha(2)beta(1) density on the platelet surface (r(2) = 0.42). Platelet adhesion to collagen types I and III depends on both plasma levels of vWF and alpha(2)beta(1) density on the platelet surface, whereas platelet adhesion to collagen type IV is mediated by both platelet vWF levels and alpha(2)beta(1) density on the platelet surface. (Blood. 2000;96:1433-1437)     

Prevalence and Correlates of Hearing and Visual Impairments in European Nursing Homes: Results From the SHELTER Study

Background

Visual and hearing impairments are known to be related to functional disability, cognitive impairment, and depression in community-dwelling older people. The aim of this study was to examine the prevalence of sensory impairment in nursing home residents, and whether sensory impairment is related to other common clinical problems in nursing homes, mediated by functional disability, cognitive impairment, and depressive symptoms.

Methods

Cross-sectional data of 4007 nursing home residents in 59 facilities in 8 countries from the SHELTER study were analyzed. Visual and hearing impairments were assessed by trained staff using the interRAI instrument for Long-Term Care Facilities. Generalized linear mixed models adjusted for functional disability, cognitive impairment, and depressive symptoms were used to analyze associations of sensory impairments with prevalence of clinical problems, including behavioral symptoms, incontinence, fatigue, falls, problems with balance, sleep, nutrition, and communication.

Results

Of the participants, 32% had vision or hearing impairment (single impairment) and another 32% had both vision and hearing impairments (dual impairment). Residents with single impairment had significantly higher rates of communication problems, fatigue, balance problems, and sleep problems, as compared with residents without any sensory impairment. Those with dual impairment had significantly higher rates of all clinical problems assessed in this study as compared with those without sensory impairment. For each clinical problem, the magnitude of the odds ratio for specific clinical problems was higher for dual impairment than for single impairment.

Conclusion

Visual and hearing impairments are associated with higher rates of common clinical problems among nursing home residents, independent of functional disability, cognitive impairment, and depressive symptoms.