Medically Biodegradable Hydrogenated Amorphous Silicon Microspheres

[EN] Hydrogenated amorphous silicon colloids of low surface area (<5 m(2)/g) are shown to exhibit complete in-vitro biodegradation into orthosilicic acid within 10-15 days at 37 degrees C. When converted into polycrystalline silicon colloids, by high temperature annealing in an inert atmosphere, microparticle solubility is dramatically reduced. The data suggests that amorphous silicon does not require nanoscale porosification for full in-vivo biodegradability. This has significant implications for using a-Si:H coatings for medical implants in general, and orthopedic implants in particular. The high sphericity and biodegradability of submicron particles may also confer advantages with regards to contrast agents for medical imaging.This work has been partially supported by the Spanish CICyT projects, FIS2009-07812, Consolider CSD2007-046, MAT2009-010350 and PROMETEO/2010/043.Shabir, Q.; Pokale, A.; Loni, A.; Johnson, DR.; Canham, L.; Fenollosa Esteve, R.; Tymczenko, MK.... (2011). Medically Biodegradable Hydrogenated Amorphous Silicon Microspheres. Silicon. 3(4):173-176. https://doi.org/10.1007/s12633-011-9097-4S17317634Salonen J, Kaukonen AM, Hirvonen J, Lehto VP (2008) J Pharmaceutics 97:632–53Anglin EJ, Cheng L, Freeman WR, Sailor MJ (2008) Adv Drug Deliv Rev 60:1266–77O’Farrell N, Houlton A, Horrocks BR (2006) Int J Nanomedicine 1:451–72Canham LT (1995) Adv Mater 7:1037, PCT patent WO 97/06101,1999Park JH, Gui L, Malzahn G, Ruoslahti E, Bhatia SN, Sailor MJ (2009) Nature Mater 8:331–6Cullis AG, Canham LT, Calcott PDJ (1997) J Appl Phys 82:909–66Canham LT, Reeves CR (1996) Mat Res Soc Symp 414:189–90Edell DJ, Toi VV, McNeil VM, Clark LD (1992) IEEE Trans Biomed Eng 39:635–43Fenollosa R, Meseguer F, Tymczenko M (2008) Adv Mater 20:95Fenollosa R, Meseguer F, Tymczenko M, Spanish Patent P200701681, 2007Pell LE, Schricker AD, Mikulec FV, Korgel BA (2004) Langmuir 20:6546Xifré-Perez E, Fenollosa R, Meseguer F (2011) Opt Express 19:3455–63Fenollosa R, Ramiro-Manzano F, Tymczenko M, Meseguer F (2010) J Mater Chem 20:5210Xifré-Pérez E, Domenech JD, Fenollosa R, Muñoz P, Capmany J, Meseguer F (2011) Opt Express 19–4:3185–92Rodriguez I, Fenollosa R, Meseguer F, Cosmetics & Toiletries 2010;42–49Ramiro-Manzano F, Fenollosa R, Xifré-Pérez E, Garín M, Meseguer F (2011) Adv Mater 23:3022–3025. doi: 10.1002/adma.201100986Iler RK (1979) Chemistry of silica: solubility, polymerization, colloid & surface properties & biochemistry. Wiley, New YorkTanaka K, Maruyama E, Shimado T, Okamoto H (1999) Amorphous silicon. Wiley, New York, NYPatterson AL (1939) Phys Rev 56:978–82Canham LT, Reeves CL, King DO, Branfield PJ, Gabb JG, Ward MC (1996) Adv Mater 8:850–2Iler RK In: Chemistry of silica: solubility, polymerization, colloid & surface properties &Biochemistry. Wiley, New York, NYFinnie KS, Waller DJ, Perret FL, Krause-Heuer AM, Lin HQ, Hanna JV, Barbe CJ (2009) J Sol-Gel Technol 49:12–8Zhao D, Huo Q, Feng J, Chmelka BF, Stucky GD (1998) J Am Chem Soc 120:6024–36Fan D, Akkaraju GR, Couch EF, Canham LT, Coffer JL (2010) Nanoscale 1:354–61Tasciotti E, Godin B, Martinez JO, Chiappini C, Bhavane R, Liu X, Ferrari M (2011) Mol Imaging 10:56–

Detection of Bioactive Exometabolites Produced by the Filamentous Marine Cyanobacterium Geitlerinema sp.

Marine cyanobacteria are noted for their ability to excrete metabolites with biotic properties. This paper focuses on such exometabolites obtained from the culture of the marine filamentous cyanobacterium Geitlerinema sp. strain, their purification and subsequent analyses. By this means the recoveries of the active compounds, a prerequisite for properly determining their concentration, are quantified here for the first time. We demonstrate a new procedure using Amberlite XAD-1180 resin in combination with the eluent isopropanol for extraction of the culture media and gas chromatography as simplified chemical analysis. This procedure reduced necessary bacteria cultivation time (from 150 to 21 days) at low volumes of culture media (300 mL) required for identification of two selected bioactive compounds: 4,4′-dihydroxybiphenyl and harmane

Listening In on the Past: What Can Otolith δ18O Values Really Tell Us about the Environmental History of Fishes?

Oxygen isotope ratios from fish otoliths are used to discriminate marine stocks and reconstruct past climate, assuming that variations in otolith δ18O values closely reflect differences in temperature history of fish when accounting for salinity induced variability in water δ18O. To investigate this, we exploited the environmental and migratory data gathered from a decade using archival tags to study the behaviour of adult plaice (Pleuronectes platessa L.) in the North Sea. Based on the tag-derived monthly distributions of the fish and corresponding temperature and salinity estimates modelled across three consecutive years, we first predicted annual otolith δ18O values for three geographically discrete offshore sub-stocks, using three alternative plausible scenarios for otolith growth. Comparison of predicted vs. measured annual δ18O values demonstrated >96% correct prediction of sub-stock membership, irrespective of the otolith growth scenario. Pronounced inter-stock differences in δ18O values, notably in summer, provide a robust marker for reconstructing broad-scale plaice distribution in the North Sea. However, although largely congruent, measured and predicted annual δ18O values of did not fully match. Small, but consistent, offsets were also observed between individual high-resolution otolith δ18O values measured during tag recording time and corresponding δ18O predictions using concomitant tag-recorded temperatures and location-specific salinity estimates. The nature of the shifts differed among sub-stocks, suggesting specific vital effects linked to variation in physiological response to temperature. Therefore, although otolith δ18O in free-ranging fish largely reflects environmental temperature and salinity, we counsel prudence when interpreting otolith δ18O data for stock discrimination or temperature reconstruction until the mechanisms underpinning otolith δ18O signature acquisition, and associated variation, are clarified

Implementing resilience engineering for healthcare quality improvement using the CARE model: a feasibility study protocol

BACKGROUND: Resilience engineering (RE) is an emerging perspective on safety in complex adaptive systems that emphasises how outcomes emerge from the complexity of the clinical environment. Complexity creates the need for flexible adaptation to achieve outcomes. RE focuses on understanding the nature of adaptations, learning from success and increasing adaptive capacity. Although the philosophy is clear, progress in applying the ideas to quality improvement has been slow. The aim of this study is to test the feasibility of translating RE concepts into practical methods to improve quality by designing, implementing and evaluating interventions based on RE theory. The CARE model operationalises the key concepts and their relationships to guide the empirical investigation. METHODS: The settings are the Emergency Department and the Older Person's Unit in a large London teaching hospital. Phases 1 and 2 of our work, leading to the development of interventions to improve the quality of care, are described in this paper. Ethical approval has been granted for these phases. Phase 1 will use ethnographic methods, including observation of work practices and interviews with staff, to understand adaptations and outcomes. The findings will be used to collaboratively design, with clinical staff in interactive design workshops, interventions to improve the quality of care. The evaluation phase will be designed and submitted for ethical approval when the outcomes of phases 1 and 2 are known. DISCUSSION: Study outcomes will be knowledge about the feasibility of applying RE to improve quality, the development of RE theory and a validated model of resilience in clinical work which can be used to guide other applications. Tools, methods and practical guidance for practitioners will also be produced, as well as specific knowledge of the potential effectiveness of the implemented interventions in emergency and older people's care. Further studies to test the application of RE at a larger scale will be required, including studies of other healthcare settings, organisational contexts and different interventions

Progression of coronary calcification in healthy postmenopausal women

BACKGROUND: Coronary artery calcium score incrementally improves coronary risk prediction beyond that provided by conventional risk factors. Limited information is available regarding rates of progression of coronary calcification in women, particularly those with baseline scores above zero. Further, determinants of progression of coronary artery calcification in women are not well understood. This study prospectively evaluated rates and determinants of progression of coronary artery calcium score in a group of healthy postmenopausal women. METHODS: We determined coronary calcium score by computed tomography and recorded demographic, lifestyle and health characteristics of 914 postmenopausal women, a subset of those enrolled in the Women's Health Initiative Observational Study. The 305 women with calcium score ≥10 Agatston units at baseline were invited for repeat scan. This analysis includes the 94 women who underwent second scans. RESULTS: Mean age of study participants was 65 ± 9 years (mean ± SD), body mass index was 26.1 ± 6.1 kg/m(2), and baseline calcium score was 162 ± 220 Agatston units. Mean interval between scans was 3.3 ± 0.7 years. A wide range of changes in coronary calcium score was observed, from -53 to +452 Agatston units/year. Women with lower scores at baseline had smaller annual increases in absolute calcium score. Coronary calcium scores increased 11, 31 and 79 Agatston units/year among women with baseline calcium score in the lowest, middle and highest tertiles. In multivariate analysis, age was not an independent predictor of absolute change in coronary calcium score. Hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) use at baseline was a negative predictor (p = 0.015), whereas baseline calcium score was a strong, positive predictor (p < 0.0001) of progression of coronary calcification. CONCLUSION: Among postmenopausal women with coronary calcium score ≥ 10 Agatston units, rates of change of coronary calcium score varied widely. In multivariate analysis, statin use was a negative independent determinant, whereas baseline calcium score was a strong positive predictor of annual change in coronary calcium score

The Saccadic and Neurological Deficits in Type 3 Gaucher Disease

Our objective was to characterize the saccadic eye movements in patients with type 3 Gaucher disease (chronic neuronopathic) in relationship to neurological and neurophysiological abnormalities. For approximately 4 years, we prospectively followed a cohort of 15 patients with Gaucher type 3, ages 8–28 years, by measuring saccadic eye movements using the scleral search coil method. We found that patients with type 3 Gaucher disease had a significantly higher regression slope of duration vs amplitude and peak duration vs amplitude compared to healthy controls for both horizontal and vertical saccades. Saccadic latency was significantly increased for horizontal saccades only. Downward saccades were more affected than upward saccades. Saccade abnormalities increased over time in some patients reflecting the slowly progressive nature of the disease. Phase plane plots showed individually characteristic patterns of abnormal saccade trajectories. Oculo-manual dexterity scores on the Purdue Pegboard test were low in virtually all patients, even in those with normal cognitive function. Vertical saccade peak duration vs amplitude slope significantly correlated with IQ and with the performance on the Purdue Pegboard but not with the brainstem and somatosensory evoked potentials. We conclude that, in patients with Gaucher disease type 3, saccadic eye movements and oculo-manual dexterity are representative neurological functions for longitudinal studies and can probably be used as endpoints for therapeutic clinical trials

Mental health: A cause or consequence of injury? A population-based matched cohort study

BACKGROUND: While a number of studies report high prevalence of mental health problems among injured people, the temporal relationship between injury and mental health service use has not been established. This study aimed to quantify this relationship using 10 years of follow-up on a population-based cohort of hospitalised injured adults. METHODS: The Manitoba Injury Outcome Study is a retrospective population-based matched cohort study that utilised linked administrative data from Manitoba, Canada, to identify an inception cohort (1988–1991) of hospitalised injured cases (ICD-9-CM 800–995) aged 18–64 years (n = 21,032), which was matched to a non-injured population-based comparison group (n = 21,032). Pre-injury comorbidity and post-injury mental health data were obtained from hospital and physician claims records. Negative Binomial regression was used to estimate adjusted rate ratios (RRs) to measure associations between injury and mental health service use. RESULTS: Statistically significant differences in the rates of mental health service use were observed between the injured and non-injured, for the pre-injury year and every year of the follow-up period. The injured cohort had 6.56 times the rate of post-injury mental health hospitalisations (95% CI 5.87, 7.34) and 2.65 times the rate of post-injury mental health physician claims (95% CI 2.53, 2.77). Adjusting for comorbidities and pre-existing mental health service use reduced the hospitalisations RR to 3.24 (95% CI 2.92, 3.60) and the physician claims RR to 1.53 (95% CI 1.47, 1.59). CONCLUSION: These findings indicate the presence of pre-existing mental health conditions is a potential confounder when investigating injury as a risk factor for subsequent mental health problems. Collaboration with mental health professionals is important for injury prevention and care, with ongoing mental health support being a clearly indicated service need by injured people and their families. Public health policy relating to injury prevention and control needs to consider mental health strategies at the primary, secondary and tertiary level

The Impact of Divergence Time on the Nature of Population Structure: An Example from Iceland

The Icelandic population has been sampled in many disease association studies, providing a strong motivation to understand the structure of this population and its ramifications for disease gene mapping. Previous work using 40 microsatellites showed that the Icelandic population is relatively homogeneous, but exhibits subtle population structure that can bias disease association statistics. Here, we show that regional geographic ancestries of individuals from Iceland can be distinguished using 292,289 autosomal single-nucleotide polymorphisms (SNPs). We further show that subpopulation differences are due to genetic drift since the settlement of Iceland 1100 years ago, and not to varying contributions from different ancestral populations. A consequence of the recent origin of Icelandic population structure is that allele frequency differences follow a null distribution devoid of outliers, so that the risk of false positive associations due to stratification is minimal. Our results highlight an important distinction between population differences attributable to recent drift and those arising from more ancient divergence, which has implications both for association studies and for efforts to detect natural selection using population differentiation

Hox10 Genes Function in Kidney Development in the Differentiation and Integration of the Cortical Stroma

Organogenesis requires the differentiation and integration of distinct populations of cells to form a functional organ. In the kidney, reciprocal interactions between the ureter and the nephrogenic mesenchyme are required for organ formation. Additionally, the differentiation and integration of stromal cells are also necessary for the proper development of this organ. Much remains to be understood regarding the origin of cortical stromal cells and the pathways involved in their formation and function. By generating triple mutants in the Hox10 paralogous group genes, we demonstrate that Hox10 genes play a critical role in the developing kidney. Careful examination of control kidneys show that Foxd1-expressing stromal precursor cells are first observed in a cap-like pattern anterior to the metanephric mesenchyme and these cells subsequently integrate posteriorly into the kidney periphery as development proceeds. While the initial cap-like pattern of Foxd1-expressing cortical stromal cells is unaffected in Hox10 mutants, these cells fail to become properly integrated into the kidney, and do not differentiate to form the kidney capsule. Consistent with loss of cortical stromal cell function, Hox10 mutant kidneys display reduced and aberrant ureter branching, decreased nephrogenesis. These data therefore provide critical novel insights into the cellular and genetic mechanisms governing cortical cell development during kidney organogenesis. These results, combined with previous evidence demonstrating that Hox11 genes are necessary for patterning the metanephric mesenchyme, support a model whereby distinct populations in the nephrogenic cord are regulated by unique Hox codes, and that differential Hox function along the AP axis of the nephrogenic cord is critical for the differentiation and integration of these cell types during kidney organogenesis