Injectable biomimetic hydrogels have great potential for use in regenerative medicine as cellular delivery vectors. However, they can suffer from issues relating to hypoxia, including poor cell ...survival, differentiation, and functional integration owing to the lack of an established vascular network. Here we engineer a hybrid myoglobin:peptide hydrogel that can concomitantly deliver stem cells and oxygen to the brain to support engraftment until vascularisation can occur naturally. We show that this hybrid hydrogel can modulate cell fate specification within progenitor cell grafts, resulting in a significant increase in neuronal differentiation. We find that the addition of myoglobin to the hydrogel results in more extensive innervation within the host tissue from the grafted cells, which is essential for neuronal replacement strategies to ensure functional synaptic connectivity. This approach could result in greater functional integration of stem cell-derived grafts for the treatment of neural injuries and diseases affecting the central and peripheral nervous systems.
The development of adaptive nanomaterials that are responsive to changes in their surrounding environment would enable such materials to be used in wide range of applications such as drug delivery ...vehicles or biosensors. Reversible boronic ester chemistry, which is used in this work, has several advantages as a building block for making adaptive nanomaterials including the ease of preparation, high sensitivity to external stimuli such as pH, and relative stability especially when compared to other non-covalent reversible systems. Herein, by using small boronic acids as anchor and peptides as connectors, we report progress in the initial development of novel, peptidyl-based pH dependent adaptive nanomaterials using reversible boronic ester chemistry and its characterisation using small angle X-ray scattering.
Microarray genome analysis is realising its promise for improving detection of genetic abnormalities in individuals with mental retardation and congenital abnormality. Copy number variations (CNVs) ...are now readily detectable using a variety of platforms and a major challenge is the distinction of pathogenic from ubiquitous, benign polymorphic CNVs. The aim of this study was to investigate replacement of time consuming, locus specific testing for specific microdeletion and microduplication syndromes with microarray analysis, which theoretically should detect all known syndromes with CNV aetiologies as well as new ones.
Genome wide copy number analysis was performed on 117 patients using Affymetrix 250K microarrays.
434 CNVs (195 losses and 239 gains) were found, including 18 pathogenic CNVs and 9 identified as "potentially pathogenic". Almost all pathogenic CNVs were larger than 500 kb, significantly larger than the median size of all CNVs detected. Segmental regions of loss of heterozygosity larger than 5 Mb were found in 5 patients.
Genome microarray analysis has improved diagnostic success in this group of patients. Several examples of recently discovered "new syndromes" were found suggesting they are more common than previously suspected and collectively are likely to be a major cause of mental retardation. The findings have several implications for clinical practice. The study revealed the potential to make genetic diagnoses that were not evident in the clinical presentation, with implications for pretest counselling and the consent process. The importance of contributing novel CNVs to high quality databases for genotype-phenotype analysis and review of guidelines for selection of individuals for microarray analysis is emphasised.
Anionic dimyristoylphosphatidic acid monolayers spread on LaCl3 solutions reveal strong cation adsorption and a sharp transition to surface overcharging at unexpectedly low bulk salt concentrations. ...We determine the surface accumulation of La3+ with anomalous x-ray reflectivity and find that La3+ compensates the lipid surface charge by forming a Stern layer with approximately 1 La3+ ion per 3 lipids below a critical bulk concentration, ct approximately 500 nM. Above ct, the surface concentration of La3+ increases to a saturation level with approximately 1 La3+ per lipid, thus implying that the total electric charge of the La3+ exceeds the surface charge. This overcharge is observed at approximately 4 orders of magnitude lower concentration than predicted in ion-ion correlation theories. We suggest that transverse electrostatic correlations between mobile ions and surface charges (interfacial Bjerrum pairing) may contribute to the charge inversion.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
An acute-care visit for asthma often signals a management failure. Although a written action plan is effective when combined with self-management education and regular medical review, its independent ...value remains controversial.
We examined the efficacy of providing a written action plan coupled with a prescription (WAP-P) to improve adherence to medications and other recommendations in a busy emergency department.
We randomized 219 children aged 1-17 years to receive WAP-P (n = 109) or unformatted prescription (UP) (n = 110). All received fluticasone and albuterol inhalers, fitted with dose counters, to use at the discretion of the emergency physician. The main outcome was adherence to fluticasone (use/prescribed × 100%) over 28 days. Secondary outcomes included pharmacy dispensation of oral corticosteroids, β(2)-agonist use, medical follow-up, asthma education, acute-care visits, and control.
Although both groups showed a similar drop in adherence in the initial 14 days, adherence to fluticasone was significantly higher over Days 15-28 in children receiving WAP-P (mean group difference, 16.13% 2.09, 29.91). More WAP-P than UP patients filled their oral corticosteroid prescription (relative risk, 1.31 1.07, 1.60) and were well-controlled at 28 days (1.39 1.04, 1.86). Compared with UP, use of WAP-P increased physicians' prescription of maintenance fluticasone (2.47 1.53, 3.99) and recommendation for medical follow-up (1.87 1.48, 2.35), without group differences in other outcomes.
Provision of a written action plan significantly increased patient adherence to inhaled and oral corticosteroids and asthma control and physicians' recommendation for maintenance fluticasone and medical follow-up, supporting its independent value in the acute-care setting. Clinical trial registered with www.clinicaltrials.gov (NCT 00381355).
Objective
Several studies have already shown the superiority of chromosomal microarray analysis (CMA) compared with conventional karyotyping for prenatal investigation of fetal ultrasound ...abnormality. This study used very high‐resolution single nucleotide polymorphism (SNP) arrays to determine the impact on detection rates of all clinical categories of copy number variations (CNVs), and address the issue of interpreting and communicating findings of uncertain or unknown clinical significance, which are to be expected at higher frequency when using very high‐resolution CMA.
Design
Prospective validation study.
Setting
Tertiary clinical genetics centre.
Population
Women referred for further investigation of fetal ultrasound anomaly.
Methods
We prospectively tested 104 prenatal samples using both conventional karyotyping and high‐resolution arrays.
Main outcome measures
The detection rates for each clinical category of CNV.
Results
Unequivocal pathogenic CNVs were found in six cases, including one with uniparental disomy (paternal UPD 14). A further four cases had a ‘likely pathogenic’ finding. Overall, CMA improved the detection of ‘pathogenic’ and ‘likely pathogenic’ abnormalities from 2.9% (3/104) to 9.6% (10/104). CNVs of ‘unknown’ clinical significance that presented interpretational difficulties beyond results from parental investigations were detected in 6.7% (7/104) of samples.
Conclusions
Increased detection sensitivity appears to be the main benefit of high‐resolution CMA. Despite this, in this cohort there was no significant benefit in terms of improving detection of small pathogenic CNVs. A potential disadvantage is the high detection rate of CNVs of ‘unknown’ clinical significance. These findings emphasise the importance of establishing an evidence‐based policy for the interpretation and reporting of CNVs, and the need to provide appropriate pre‐ and post‐test counselling.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We have observed stable layered structures adsorbed at the silicon−water and air−water interfaces from N,N-didodecyl-N,N-dimethylammonium bromide surfactant (DDAB) and the corresponding diundecyl ...compound (DUDAB). The structures were studied by neutron reflection at the wet hydrophilic silicon interface, and at the air−water interface, at concentrations of 0.2−2% w/w. The structures formed are found to have a high sensitivity to temperature, with the repeat spacing decreasing approximately reversibly by about 50% with an increase of temperature of about 40 °C. Associated with the specular scattering there is pronounced off-specular scattering, indicative of a degree of lateral structure or dynamic fluctuation. The observations are consistent with two to four correlated layers which could arise from adsorbed monodisperse unilamellar vesicles, a lamellar phase, or a structured bicontinuous phase. Studies of the bulk solutions with X-ray scattering and cryo transmission electron microscopy show only coexisting unilamellar vesicles and lamellar phase.
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IJS, KILJ, NUK, PNG, UL, UM
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