770 research outputs found

    Mesenchymal stem cell therapies for intervertebral disc degeneration: consideration of the degenerate niche

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    We have previously reported a synthetic Laponite® crosslinked pNIPAM‐co‐DMAc (NPgel) hydrogel, which induces nucleus pulposus (NP) cell differentiation of human MSCs (hMSCs) without the need for additional growth factors. Furthermore NP gel supports integration following injection into the disc and restores mechanical function to the disc. However, translation of this treatment strategy into clinical application is dependent on the survival and differentiation of hMSC to the correct cell phenotype within the degenerate IVD. Here, we investigated the viability and differentiation of hMSCs within NP gel within a catabolic microenvironment. Human MSCs were encapsulated in NPgel and cultured for 4 weeks under hypoxia (5% O2) with ± calcium, IL‐1β and TNFα either individually or in combination to mimic the degenerate environment. Cell viability, and cellular phenotype was investigated. Stem cell viability was maintained within hydrogel systems for the 4 weeks investigated under all degenerate conditions. NP matrix markers: Agg and Col II and NP phenotypic markers: HIF‐1α, FOXF1 and PAX1 were expressed within the NPgel cultures and expression was not affected by culture within degenerate conditions. Alizarin red staining demonstrated increased calcium deposition under cultures containing CaCl2 indicating calcification of the matrix. Interestingly MMP's, ADAMTS 4 and Col I expression by hMSCs cultured in NPgel was upregulated by calcium but not by pro‐inflammatory cytokines IL‐1β and TNFα. Importantly IL‐1β and TNFα, regarded as key contributors to disc degeneration, were not shown to affect the NP cell differentiation of MSCs in the NPgel. In agreement with our previous findings, NPgel alone was sufficient to induce NP cell differentiation of MSCs, with expression of both aggrecan and collagen type II, under both standard and degenerate culture conditions; thus could provide a therapeutic option for the repair of the NP during IVD degeneration

    Emergence of skew distributions in controlled growth processes

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    Starting from a master equation, we derive the evolution equation for the size distribution of elements in an evolving system, where each element can grow, divide into two, and produce new elements. We then probe general solutions of the evolution quation, to obtain such skew distributions as power-law, log-normal, and Weibull distributions, depending on the growth or division and production. Specifically, repeated production of elements of uniform size leads to power-law distributions, whereas production of elements with the size distributed according to the current distribution as well as no production of new elements results in log-normal distributions. Finally, division into two, or binary fission, bears Weibull distributions. Numerical simulations are also carried out, confirming the validity of the obtained solutions.Comment: 9 pages, 3 figure

    Compatibilization of highly sustainable polylactide/almond shell flour composites by reactive extrusion with maleinized linseed oil

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    Highly sustainable composites were produced by melt compounding polylactide (PLA) with almond shell flour (ASF), a processed by-product of the food industry, at a constant weight content of 30 wt.-%. However, due to the lack of miscibility between PLA and ASF, both being raw materials obtained from crops, resultant green composite presented poor ductility and low thermal stability. To overcome this limitation, maleinized linseed oil (MLO), a multi-functionalized plant-derived additive, was originally incorporated as a reactive compatibilizer during the extrusion process. Both chemical and physical characterizations showed that 1–5 parts per hundred resin (phr) of MLO successfully serve to obtain PLA/ASF composites with improved mechanical, thermal, and thermomechanical properties. The enhancement achieved was particularly related to a dual compatibilizing effect of plasticization in combination with melt grafting. The latter process was specifically ascribed to the formation of new carboxylic ester bonds through the reaction of the multiple maleic anhydride functionalities present in MLO with the hydroxyl groups of both the PLA terminal chains and cellulose on the ASF surface. The fully bio-based and biodegradable composites described herein give an efficient sustainable solution to upgrade agro-food wastes as well as contributing to reducing the cost of PLA-based materials

    Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records.

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    BACKGROUND: Although many women treated with psychotropic medication become pregnant, no psychotropic medication has been licensed for use in pregnancy. This leaves women and their health-care professionals in a treatment dilemma, as they need to balance the health of the woman with that of the unborn child. The aim of this project was to investigate the risks and benefits of psychotropic medication in women treated for psychosis who become pregnant. OBJECTIVE(S): (1) To provide a descriptive account of psychotropic medication prescribed before pregnancy, during pregnancy and up to 15 months after delivery in UK primary care from 1995 to 2012; (2) to identify risk factors predictive of discontinuation and restarting of lithium (multiple manufacturers), anticonvulsant mood stabilisers and antipsychotic medication; (3) to examine the extent to which pregnancy is a determinant for discontinuation of psychotropic medication; (4) to examine prevalence of records suggestive of adverse mental health, deterioration or relapse 18 months before and during pregnancy, and up to 15 months after delivery; and (5) to estimate absolute and relative risks of adverse maternal and child outcomes of psychotropic treatment in pregnancy. DESIGN: Retrospective cohort studies. SETTING: Primary care. PARTICIPANTS: Women treated for psychosis who became pregnant, and their children. INTERVENTIONS: Treatment with antipsychotics, lithium or anticonvulsant mood stabilisers. MAIN OUTCOME MEASURES: Discontinuation and restarting of treatment; worsening of mental health; acute pre-eclampsia/gestational hypertension; gestational diabetes; caesarean section; perinatal death; major congenital malformations; poor birth outcome (low birthweight, preterm birth, small for gestational age, low Apgar score); transient poor birth outcomes (tremor, agitation, breathing and muscle tone problems); and neurodevelopmental and behavioural disorders. DATA SOURCES: Clinical Practice Research Datalink database and The Health Improvement Network primary care database. RESULTS: Prescribing of psychotropic medication was relatively constant before pregnancy, decreased sharply in early pregnancy and peaked after delivery. Antipsychotic and anticonvulsant treatment increased over the study period. The recording of markers of worsening mental health peaked after delivery. Pregnancy was a strong determinant for discontinuation of psychotropic medication. However, between 40% and 76% of women who discontinued psychotropic medication before or in early pregnancy restarted treatment by 15 months after delivery. The risk of major congenital malformations, and neurodevelopmental and behavioural outcomes in valproate (multiple manufacturers) users was twice that in users of other anticonvulsants. The risks of adverse maternal and child outcomes in women who continued antipsychotic use in pregnancy were not greater than in those who discontinued treatment before pregnancy. LIMITATIONS: A few women would have received parts of their care outside primary care, which may not be captured in this analysis. Likewise, the analyses were based on prescribing data, which may differ from usage. CONCLUSIONS: Psychotropic medication is prescribed before, during and after pregnancy. Many women discontinue treatment before or during early pregnancy and then restart again in late pregnancy or after delivery. Our results support previous associations between valproate and adverse child outcomes but we found no evidence of such an association for antipsychotics. FUTURE WORK: Future research should focus on (1) curtailing the use of sodium valproate; (2) estimating the benefits of psychotropic drug use in pregnancy; and (3) investigating the risks associated with lifestyle choices that are more prevalent among women using psychotropic drugs. FUNDING DETAILS: The National Institute for Health Research Health Technology Assessment programme

    Two rapid assays for screening of patulin biodegradation

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    Artículo sobre distintos ensayos para comprobar la biodegradación de la patulinaThe mycotoxin patulin is produced by the blue mould pathogen Penicillium expansum in rotting apples during postharvest storage. Patulin is toxic to a wide range of organisms, including humans, animals, fungi and bacteria. Wash water from apple packing and processing houses often harbours patulin and fungal spores, which can contaminate the environment. Ubiquitous epiphytic yeasts, such as Rhodosporidium kratochvilovae strain LS11 which is a biocontrol agent of P. expansum in apples, have the capacity to resist the toxicity of patulin and to biodegrade it. Two non-toxic products are formed. One is desoxypatulinic acid. The aim of the work was to develop rapid, high-throughput bioassays for monitoring patulin degradation in multiple samples. Escherichia coli was highly sensitive to patulin, but insensitive to desoxypatulinic acid. This was utilized to develop a detection test for patulin, replacing time-consuming thin layer chromatography or high-performance liquid chromatography. Two assays for patulin degradation were developed, one in liquid medium and the other in semi-solid medium. Both assays allow the contemporary screening of a large number of samples. The liquid medium assay utilizes 96-well microtiter plates and was optimized for using a minimum of patulin. The semisolid medium assay has the added advantage of slowing down the biodegradation, which allows the study and isolation of transient degradation products. The two assays are complementary and have several areas of utilization, from screening a bank of microorganisms for biodegradation ability to the study of biodegradation pathways

    On the upstream mobility scheme for two-phase flow in porous media

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    When neglecting capillarity, two-phase incompressible flow in porous media is modelled as a scalar nonlinear hyperbolic conservation law. A change in the rock type results in a change of the flux function. Discretizing in one-dimensional with a finite volume method, we investigate two numerical fluxes, an extension of the Godunov flux and the upstream mobility flux, the latter being widely used in hydrogeology and petroleum engineering. Then, in the case of a changing rock type, one can give examples when the upstream mobility flux does not give the right answer.Comment: A preprint to be published in Computational Geoscience

    Squamous cancer of the oesophagus in Africa: A change of focus for research

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