Adherence to medication in adults with Cystic Fibrosis: An investigation using objective adherence data and the Theoretical Domains Framework

Objectives Adherence to nebulizer treatment in adults with Cystic Fibrosis (CF) is poor, and interventions are needed. This research aimed to identify the factors affecting nebulizer adherence using the Theoretical Domains Framework (TDF) and to compare these for participants with different levels of adherence. Design Data‐prompted interviews using the TDF. Methods Eighteen semi‐structured interviews were conducted with adults with CF during which objectively measured adherence data were discussed. Framework analysis was used to code the data into TDF domains, and inductive qualitative content analysis was used to code different beliefs and experiences. Aspects of the TDF that differed between participants with different adherence levels were explored. Results Factors influencing adherence to treatment included all 14 domains of the TDF, 10 of which appeared to vary by adherence level: Skills; Memory and decision‐making; and Behavioural regulation; Environmental context and resources; Social influences; Beliefs about consequences; Beliefs about capability; Reinforcement; Social role and identify; Intentions; Optimism; and Emotions. Conclusions This study is the first to use objectively measured adherence data in a data‐prompted interview using the TDF framework to systematically assess the full range of factors potentially influencing adherence. The results highlighted that interventions need to consider issues of capability, opportunity, and motivation. Interventions that challenge dysfunctional beliefs about adherence and which support the development of routines or habits and problem‐solving may be particularly useful for adults with CF

Seed production and germination in endangered Nuphar（Nymphaeaceae）of western Japan

Populations of both Nuphar pumila subsp. oguraensis and the partially fertile hybrid N．×saijoensis are rare throughout their range. In an aim to identify factors that might influence conservation strategies, seed produc-tion and viability were evaluated in these two imperiled taxa and the more common N . japonica within the Saijô Basin, western Japan. Seed production was significantly higher per fruit in N. japonica and the lowest in N． ×saijoensis. Seed germination did not differ significantly between taxa, however the overall seed viability of the three Japanese taxa was low in comparison to other Nuphar taxa. Our findings suggest that seed viability is not a factor contributing greatly to the rarity of the Nuphar in the Saijô Basin. Fruit and seed harvesting techniques offer potential for propagation efforts

Ecology, behaviour and management of the European catfish

The extreme body sizes of ‘megafishes’ associated with their high commercial values and recreational interests have made them highly threatened in their native range worldwide by human-induced impacts such as overexploitation. Meanwhile, and because of the aforementioned interests, some megafishes have been introduced outside of their native range. A notable exampled is the European catfish (Silurus glanis), one of the few siluriforms native from western Europe and among the 10 largest freshwater fish worldwide, attaining a total length over 2.7 m and a documented mass of 130 kg. Its distinct phylogeny and extreme size imply many features rare among other European fish such as peculiar behaviours (massive aggregations, beaching), consumption of large bodied prey, fast growth rate, long lifespan, high fecundity, nest guarding and large eggs. The spread of the species is likely to continue due to illegal introduction coupled with natural range extension due to current and future climate change. Based on these attributes and potential future risks, this introduced giant predator in European fresh waters could provide a novel model species of high utility for testing aspects of ecological and invasion theory and associated hypotheses. Here, we reviewed the most recent knowledge on the current distribution and the ecology of the species to understand how this can help advance our understanding of biological invasions. We also identified key research questions that should help stimulating new research on this intriguing, yet largely unknown, species and, more generally, on the ecology of invasive species

Effect of fungicidal treatment and storage condition on content of selected mycotoxins in barley

The aim of the study was to determine the effect of fungicidal treatment and storage on the occurrence of mycotoxins in barley (Hordeum vulgare L.). Barley was initially inoculated with Fusarium culmorum followed by the application of fungicides (prothioconazole and bixafen). A screening of 57 mycotoxins were performed using ultra-performance liquid chromatography in tandem with mass spectrometry. The fungicide treatment affected (P <0.05) the levels of zearalenone, β-zearalenol, arternariol and alternariol-methylether that were present. Levels of deoxynivalenol was highest in the second year of monitoring. 3-acetyl-deoxynivalenol was not affected by fungicidal treatment or storage. The significant increase (P <0.05) of DON-3-glucoside, 15-acetyl-DON, enniatin A, enniatin A1, enniatin B, and enniatin B1 was measured in barley samples. The results of the experiment determined that the use of fungicides can suppress some kinds of mycotoxins, but not others

Antimalarial Iron Chelator, FBS0701, Shows Asexual and Gametocyte Plasmodium falciparum Activity and Single Oral Dose Cure in a Murine Malaria Model

Iron chelators for the treatment of malaria have proven therapeutic activity in vitro and in vivo in both humans and mice, but their clinical use is limited by the unsuitable absorption and pharmacokinetic properties of the few available iron chelators. FBS0701, (S)3”-(HO)-desazadesferrithiocin-polyether [DADFT-PE], is an oral iron chelator currently in Phase 2 human studies for the treatment of transfusional iron overload. The drug has very favorable absorption and pharmacokinetic properties allowing for once-daily use to deplete circulating free iron with human plasma concentrations in the high µM range. Here we show that FBS0701 has inhibition concentration 50% (IC50) of 6 µM for Plasmodium falciparum in contrast to the IC50 for deferiprone and deferoxamine at 15 and 30 µM respectively. In combination, FBS0701 interfered with artemisinin parasite inhibition and was additive with chloroquine or quinine parasite inhibition. FBS0701 killed early stage P. falciparum gametocytes. In the P. berghei Thompson suppression test, a single dose of 100 mg/kg reduced day three parasitemia and prolonged survival, but did not cure mice. Treatment with a single oral dose of 100 mg/kg one day after infection with 10 million lethal P. yoelii 17XL cured all the mice. Pretreatment of mice with a single oral dose of FBS0701 seven days or one day before resulted in the cure of some mice. Plasma exposures and other pharmacokinetics parameters in mice of the 100 mg/kg dose are similar to a 3 mg/kg dose in humans. In conclusion, FBS0701 demonstrates a single oral dose cure of the lethal P. yoelii model. Significantly, this effect persists after the chelator has cleared from plasma. FBS0701 was demonstrated to remove labile iron from erythrocytes as well as enter erythrocytes to chelate iron. FBS0701 may find clinically utility as monotherapy, a malarial prophylactic or, more likely, in combination with other antimalarials

SDF1 in the dorsal corticospinal tract promotes CXCR4+ cell migration after spinal cord injury

<p>Abstract</p> <p>Background</p> <p>Stromal cell-derived factor-1 (SDF1) and its major signaling receptor, CXCR4, were initially described in the immune system; however, they are also expressed in the nervous system, including the spinal cord. After spinal cord injury, the blood brain barrier is compromised, opening the way for chemokine signaling between these two systems. These experiments clarified prior contradictory findings on normal expression of SDF1 and CXCR4 as well as examined the resulting spinal cord responses resulting from this signaling.</p> <p>Methods</p> <p>These experiments examined the expression and function of SDF1 and CXCR4 in the normal and injured adult mouse spinal cord primarily using CXCR4-EGFP and SDF1-EGFP transgenic reporter mice.</p> <p>Results</p> <p>In the uninjured spinal cord, SDF1 was expressed in the dorsal corticospinal tract (dCST) as well as the meninges, whereas CXCR4 was found only in ependymal cells surrounding the central canal. After spinal cord injury (SCI), the pattern of SDF1 expression did not change rostral to the lesion but it disappeared from the degenerating dCST caudally. By contrast, CXCR4 expression changed dramatically after SCI. In addition to the CXCR4+ cells in the ependymal layer, numerous CXCR4+ cells appeared in the peripheral white matter and in the dorsal white matter localized between the dorsal corticospinal tract and the gray matter rostral to the lesion site. The non-ependymal CXCR4+ cells were found to be NG2+ and CD11b+ macrophages that presumably infiltrated through the broken blood-brain barrier. One population of macrophages appeared to be migrating towards the dCST that contains SDF1 rostral to the injury but not towards the caudal dCST in which SDF1 is no longer present. A second population of the CXCR4+ macrophages was present near the SDF1-expressing meningeal cells.</p> <p>Conclusions</p> <p>These observations suggest that attraction of CXCR4+ macrophages is part of a programmed response to injury and that modulation of the SDF1 signaling system may be important for regulating the inflammatory response after SCI.</p

Chondroitinase and Growth Factors Enhance Activation and Oligodendrocyte Differentiation of Endogenous Neural Precursor Cells after Spinal Cord Injury

The adult spinal cord harbours a population of multipotent neural precursor cells (NPCs) with the ability to replace oligodendrocytes. However, despite this capacity, proliferation and endogenous remyelination is severely limited after spinal cord injury (SCI). In the post-traumatic microenvironment following SCI, endogenous spinal NPCs mainly differentiate into astrocytes which could contribute to astrogliosis that exacerbate the outcomes of SCI. These findings emphasize a key role for the post-SCI niche in modulating the behaviour of spinal NPCs after SCI. We recently reported that chondroitin sulphate proteoglycans (CSPGs) in the glial scar restrict the outcomes of NPC transplantation in SCI by reducing the survival, migration and integration of engrafted NPCs within the injured spinal cord. These inhibitory effects were attenuated by administration of chondroitinase (ChABC) prior to NPC transplantation. Here, in a rat model of compressive SCI, we show that perturbing CSPGs by ChABC in combination with sustained infusion of growth factors (EGF, bFGF and PDGF-AA) optimize the activation and oligodendroglial differentiation of spinal NPCs after injury. Four days following SCI, we intrathecally delivered ChABC and/or GFs for seven days. We performed BrdU incorporation to label proliferating cells during the treatment period after SCI. This strategy increased the proliferation of spinal NPCs, reduced the generation of new astrocytes and promoted their differentiation along an oligodendroglial lineage, a prerequisite for remyelination. Furthermore, ChABC and GF treatments enhanced the response of non-neural cells by increasing the generation of new vascular endothelial cells and decreasing the number of proliferating macrophages/microglia after SCI. In conclusions, our data strongly suggest that optimization of the behaviour of endogenous spinal NPCs after SCI is critical not only to promote endogenous oligodendrocyte replacement, but also to reverse the otherwise detrimental effects of their activation into astrocytes which could negatively influence the repair process after SCI