626 research outputs found

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

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    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

    Twenty-four-hour oesophageal pH studies in rural Eastern Cape Province, South Africa

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    Background. Recent studies in rural Eastern Cape Province, South Africa, have shown an increased number of non-acid gastro-oesophageal reflux events, an increase in baseline gastric pH compared with other published series, and evidence suggestive of duodenogastric reflux. There are no published data on oesophageal pH in this community or in Africa.Objectives. To ascertain whether oesophageal pH in this rural community is within normal limits.Methods. We carried out 24-hour oesophageal pH/impedance studies on 91 participants. Analysis was carried out using computer software to determine 24-hour percentage times of oesophageal pH above 4, 5, 6, 7 and 8. Oesophageal pH during each episode of non-acid reflux was also recorded.Results. Participants were from Canzibe in rural Eastern Cape. Of the studies, 72 were satisfactory and showed 24-hour percentage times with an oesophageal pH >6 of 69.3/35.12/51.16 (upright/supine/total); percentage times with a pH >7 were 12.66/3.44/8.86 and those with a pH >8 were 0.48/0.21/0.37. These results are within the range of other published series. Of episodes of non-acid reflux, 90.2% were associated with an oesophageal pH of 4 - 7.Conclusions. Baseline oesophageal pH is not significantly affected by the increased numbers of non-acid gastro-oesophageal reflux events reported in this community. If there is a pathogenic effect of non-acid reflux in the Eastern Cape, it does not appear to be mediated through raised oesophageal pH.

    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

    Spin Torque Generated by Valley Hall Effect in WSe2

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    Monolayer transition metal dichalcogenides are promising materials for spintronics due to their robust spin-valley locked valence states, enabling efficient charge-to-spin conversion via valley Hall effect with non-equilibrium spins possessing long spin diffusion lengths of hundreds of nanometers. In this work, we show that the injection of a pure valley current, induced by valley Hall effect in a WSe2 monolayer, imparts a spin torque on the magnetization of an overlaid Fe or CoFe in a tunneling structure. The torque efficiency is found to be comparable to that in conventional perpendicular magnetic tunnel junctions and can be further optimized with valley Hall angle in WSe2. The valley nature of the spin torque gives rise to out-of-plane damping-like torques in a current-in-plane configuration, vanishing charge transport perpendicular-to-the-plane as well as torque efficiency tunable through gating

    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

    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
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