Efficacy of the enteroadsorbent Silicol®gel in adults with irritable bowel syndrome subtypes IBS-D or mixed : observational open-label study

Background. Irritable bowel syndrome (IBS) is a common chronic gut-brain interaction disorder with limited effective treatment options. Intestinal adsorbents have a high adsorption capacity for gut irritants and may provide nonpharmacological alternatives. Objectives. This post marketing study is aimed at providing up-to-date evidence to support the safety and efficacy in normal use of an established medical device for IBS treatment. Methods. In this open-label, observational study, adults with IBS with predominant diarrhoea (IBS-D) or IBS with mixed bowel habits (IBS-M), according to Rome IV criteria, received 4 weeks of treatment with the enteroadsorbent Silicol®gel, a CE-certified, licenced, medical device containing colloidal silicic acid. Eligible participants were assessed at baseline (visit 1; in-clinic) and after 1 (visit 2; telephone), 2 (visit 3; telephone), and 4 (visit 4; in-clinic) weeks of treatment. The primary endpoint was the proportion of participants with an overall reduction in the IBS severity scoring system IBS SSS>50, representing clinically meaningful improvement. Key secondary endpoints were a reduction in common IBS symptoms and improved quality of life (QoL). Results. Among the 67 treated participants (IBS-D: 37; IBS-M: 30), 65 completed the study. At visit 4, 83.6% (56/67) of participants achieved a reduction in IBS SSS>50. The mean (standard deviation [SD]) IBS SSS was 323.4 (55.7) at visit 1 and 160.3 (90.3) at visit 4 (overall change: -163.1 (101.7); 95% confidence interval [CI] 138.3, 187.9, p<0.001). Compared with visit 1, significant reductions in the severity of all key IBS symptoms and overall improvement in QoL were observed at visit 4 (p<0.001), with improvements observed from visits 1 and 2. Conclusions. In this open-label study of participants with IBS-D and IBS-M, Silicol®gel provided clinically significant improvement in IBS symptoms, demonstrating that enteroadsorbents may be clinically beneficial in this population

Buoys with looming eyes deter seaducks and could potentially reduce seabird bycatch in gillnets.

Bycatch of seabirds in gillnet fisheries is a global conservation issue with an estimated 400 000 seabirds killed each year. To date, no underwater deterrents trialled have consistently reduced seabird bycatch across operational fisheries. Using a combination of insights from land-based strategies, seabirds' diving behaviours and their cognitive abilities, we developed a floating device exploring the effect of large eyespots and looming movement to prevent vulnerable seabirds from diving into gillnets. Here, we tested whether this novel above-water device called 'Looming eyes buoy' (LEB) would consistently deter vulnerable seaducks from a focal area. We counted the number of birds present in areas with and without LEBs in a controlled experimental setting. We show that long-tailed duck Clangula hyemalis abundance declined by approximately 20-30% within a 50 m radius of the LEB and that the presence of LEBs was the most important variable explaining this decline. We found no evidence for a memory effect on long-tailed ducks but found some habituation to the LEB within the time frame of the project (62 days). While further research is needed, our preliminary trials indicate that above-water visual devices could potentially contribute to reduce seabird bycatch if appropriately deployed in coordination with other management measures

Buoys with looming eyes deter seaducks and could potentially reduce seabird bycatch in gillnets.

Bycatch of seabirds in gillnet fisheries is a global conservation issue with an estimated 400 000 seabirds killed each year. To date, no underwater deterrents trialled have consistently reduced seabird bycatch across operational fisheries. Using a combination of insights from land-based strategies, seabirds' diving behaviours and their cognitive abilities, we developed a floating device exploring the effect of large eyespots and looming movement to prevent vulnerable seabirds from diving into gillnets. Here, we tested whether this novel above-water device called 'Looming eyes buoy' (LEB) would consistently deter vulnerable seaducks from a focal area. We counted the number of birds present in areas with and without LEBs in a controlled experimental setting. We show that long-tailed duck Clangula hyemalis abundance declined by approximately 20-30% within a 50 m radius of the LEB and that the presence of LEBs was the most important variable explaining this decline. We found no evidence for a memory effect on long-tailed ducks but found some habituation to the LEB within the time frame of the project (62 days). While further research is needed, our preliminary trials indicate that above-water visual devices could potentially contribute to reduce seabird bycatch if appropriately deployed in coordination with other management measures

Incidental mortality of seabirds in trawl fisheries: A global review

Seabirds are amongst the most threatened taxa in the world, often due to incidental mortality (bycatch) in fisheries. Hundreds of thousands are thought to be killed worldwide in gillnets and longlines each year, but global mortality in trawl fisheries is unknown. Based on our comprehensive review, bycatch totals from cable strikes and net captures were available for only 25 fisheries. Bycatch rates were highly variable, precluding substitution from monitored to unmonitored fisheries to estimate bycatch totals, and total fishing effort was often unknown, which is also a prerequisite for scaling bycatch rates to estimate total birds killed. Ten, seven and one trawl fishery were known to catch of the order of 100s, 1000s and 10,000s of birds, respectively, and total bycatch from all monitored fisheries sums to ∼44,000 birds per year. However, given the scale of cryptic mortality and the many unmonitored or poorly monitored fisheries, the actual global mortality in trawl fisheries will be much higher. The most bycaught species were albatrosses and large petrels (many of which are threatened) in the Southern Hemisphere, and gannets in the Northern Hemisphere. The few long-term studies indicated that mitigation measures (particularly strategic offal management and bird-scaring lines) were effective at reducing bycatch rates. Much improved regulations, and close monitoring of compliance and bycatch rates are essential for ensuring trawl fisheries do not continue to have major impacts on vulnerable seabird populations

“I will commit to this child as much as I can for the time that they are with me:” a qualitative examination of how foster carer commitment relates to short-term foster care for young children following abuse and neglect

Background: Foster carer commitment to the child has been shown to be of paramount importance in young children's recovery and development following abuse and neglect. In Dozier's definition of commitment in the US, there is a focus on both emotional investment in the child and committing to an enduring relationship with the child. How this relates to the routine practice of short-term, temporary, foster care has not been studied. Objective: This is the first qualitative study to explore the drivers of, and barriers to, commitment in short-term foster care within the broader aim of examining whether short-term care is meeting the needs of maltreated young children. Participants &amp; setting: Fourteen foster carers took part in research interviews and five focus groups were conducted with infant mental health professionals. Methods: Interviews and focus group data were subject to qualitative thematic analysis in order to identify patterns of commonality in relation to our research questions. Results: Three broad themes pertain to commitment and the meeting of young children's needs in short-term foster care: Influence, Timescales and Choice in the fostering role. These themes were found to house both drivers of, and barriers to, commitment in short-term care, which are influenced by systemic normalisations of fostering practices. Conclusions: The emotional investment facet of commitment is more alive in the ‘psyche’ of short-term foster care than commitment to an enduring relationship. A long-term outlook for the child may be an undefined facet of commitment that is more akin with short-term placements

Projected Range Contractions of European Protected Oceanic Montane Plant Communities: Focus on Climate Change Impacts Is Essential for Their Future Conservation

Global climate is rapidly changing and while many studies have investigated the potential impacts of this on the distribution of montane plant species and communities, few have focused on those with oceanic montane affinities. In Europe, highly sensitive bryophyte species reach their optimum occurrence, highest diversity and abundance in the northwest hyperoceanic regions, while a number of montane vascular plant species occur here at the edge of their range. This study evaluates the potential impact of climate change on the distribution of these species and assesses the implications for EU Habitats Directive-protected oceanic montane plant communities. We applied an ensemble of species distribution modelling techniques, using atlas data of 30 vascular plant and bryophyte species, to calculate range changes under projected future climate change. The future effectiveness of the protected area network to conserve these species was evaluated using gap analysis. We found that the majority of these montane species are projected to lose suitable climate space, primarily at lower altitudes, or that areas of suitable climate will principally shift northwards. In particular, rare oceanic montane bryophytes have poor dispersal capacity and are likely to be especially vulnerable to contractions in their current climate space. Significantly different projected range change responses were found between 1) oceanic montane bryophytes and vascular plants; 2) species belonging to different montane plant communities; 3) species categorised according to different biomes and eastern limit classifications. The inclusion of topographical variables in addition to climate, significantly improved the statistical and spatial performance of models. The current protected area network is projected to become less effective, especially for specialised arctic-montane species, posing a challenge to conserving oceanic montane plant communities. Conservation management plans need significantly greater focus on potential climate change impacts, including models with higher-resolution species distribution and environmental data, to aid these communities’ long-term survival

Genomic Tools for Evolution and Conservation in the Chimpanzee: Pan troglodytes ellioti Is a Genetically Distinct Population

In spite of its evolutionary significance and conservation importance, the population structure of the common chimpanzee, Pan troglodytes, is still poorly understood. An issue of particular controversy is whether the proposed fourth subspecies of chimpanzee, Pan troglodytes ellioti, from parts of Nigeria and Cameroon, is genetically distinct. Although modern high-throughput SNP genotyping has had a major impact on our understanding of human population structure and demographic history, its application to ecological, demographic, or conservation questions in non-human species has been extremely limited. Here we apply these tools to chimpanzee population structure, using ∼700 autosomal SNPs derived from chimpanzee genomic data and a further ∼100 SNPs from targeted re-sequencing. We demonstrate conclusively the existence of P. t. ellioti as a genetically distinct subgroup. We show that there is clear differentiation between the verus, troglodytes, and ellioti populations at the SNP and haplotype level, on a scale that is greater than that separating continental human populations. Further, we show that only a small set of SNPs (10–20) is needed to successfully assign individuals to these populations. Tellingly, use of only mitochondrial DNA variation to classify individuals is erroneous in 4 of 54 cases, reinforcing the dangers of basing demographic inference on a single locus and implying that the demographic history of the species is more complicated than that suggested analyses based solely on mtDNA. In this study we demonstrate the feasibility of developing economical and robust tests of individual chimpanzee origin as well as in-depth studies of population structure. These findings have important implications for conservation strategies and our understanding of the evolution of chimpanzees. They also act as a proof-of-principle for the use of cheap high-throughput genomic methods for ecological questions

Utility of Survival Motor Neuron ELISA for Spinal Muscular Atrophy Clinical and Preclinical Analyses

Genetic defects leading to the reduction of the survival motor neuron protein (SMN) are a causal factor for Spinal Muscular Atrophy (SMA). While there are a number of therapies under evaluation as potential treatments for SMA, there is a critical lack of a biomarker method for assessing efficacy of therapeutic interventions, particularly those targeting upregulation of SMN protein levels. Towards this end we have engaged in developing an immunoassay capable of accurately measuring SMN protein levels in blood, specifically in peripheral blood mononuclear cells (PBMCs), as a tool for validating SMN protein as a biomarker in SMA.A sandwich enzyme-linked immunosorbent assay (ELISA) was developed and validated for measuring SMN protein in human PBMCs and other cell lysates. Protocols for detection and extraction of SMN from transgenic SMA mouse tissues were also developed.The assay sensitivity for human SMN is 50 pg/mL. Initial analysis reveals that PBMCs yield enough SMN to analyze from blood volumes of less than 1 mL, and SMA Type I patients' PBMCs show ∼90% reduction of SMN protein compared to normal adults. The ELISA can reliably quantify SMN protein in human and mouse PBMCs and muscle, as well as brain, and spinal cord from a mouse model of severe SMA.This SMN ELISA assay enables the reliable, quantitative and rapid measurement of SMN in healthy human and SMA patient PBMCs, muscle and fibroblasts. SMN was also detected in several tissues in a mouse model of SMA, as well as in wildtype mouse tissues. This SMN ELISA has general translational applicability to both preclinical and clinical research efforts

Stochastic Modeling of B Lymphocyte Terminal Differentiation and Its Suppression by Dioxin

<p>Abstract</p> <p>Background</p> <p>Upon antigen encounter, naïve B lymphocytes differentiate into antibody-secreting plasma cells. This humoral immune response is suppressed by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other dioxin-like compounds, which belong to the family of aryl hydrocarbon receptor (AhR) agonists.</p> <p>Results</p> <p>To achieve a better understanding of the immunotoxicity of AhR agonists and their associated health risks, we have used computer simulations to study the behavior of the gene regulatory network underlying B cell terminal differentiation. The core of this network consists of two coupled double-negative feedback loops involving transcriptional repressors Bcl-6, Blimp-1, and Pax5. Bifurcation analysis indicates that the feedback network can constitute a bistable system with two mutually exclusive transcriptional profiles corresponding to naïve B cells and plasma cells. Although individual B cells switch to the plasma cell state in an all-or-none fashion when stimulated by the polyclonal activator lipopolysaccharide (LPS), stochastic fluctuations in gene expression make the switching event probabilistic, leading to heterogeneous differentiation response among individual B cells. Moreover, stochastic gene expression renders the dose-response behavior of a population of B cells substantially graded, a result that is consistent with experimental observations. The steepness of the dose response curve for the number of plasma cells formed vs. LPS dose, as evaluated by the apparent Hill coefficient, is found to be inversely correlated to the noise level in Blimp-1 gene expression. Simulations illustrate how, through AhR-mediated repression of the AP-1 protein, TCDD reduces the probability of LPS-stimulated B cell differentiation. Interestingly, stochastic simulations predict that TCDD may destabilize the plasma cell state, possibly leading to a reversal to the B cell phenotype.</p> <p>Conclusion</p> <p>Our results suggest that stochasticity in gene expression, which renders a graded response at the cell population level, may have been exploited by the immune system to launch humoral immune response of a magnitude appropriately tuned to the antigen dose. In addition to suppressing the initiation of the humoral immune response, dioxin-like compounds may also disrupt the maintenance of the acquired immunity.</p

Adenovirus Gene Transfer to Amelogenesis Imperfecta Ameloblast-Like Cells

To explore gene therapy strategies for amelogenesis imperfecta (AI), a human ameloblast-like cell population was established from third molars of an AI-affected patient. These cells were characterized by expression of cytokeratin 14, major enamel proteins and alkaline phosphatase staining. Suboptimal transduction of the ameloblast-like cells by an adenovirus type 5 (Ad5) vector was consistent with lower levels of the coxsackie-and-adenovirus receptor (CAR) on those cells relative to CAR-positive A549 cells. To overcome CAR -deficiency, we evaluated capsid-modified Ad5 vectors with various genetic capsid modifications including “pK7” and/or “RGD” motif-containing short peptides incorporated in the capsid protein fiber as well as fiber chimera with the Ad serotype 3 (Ad3) fiber “knob” domain. All fiber modifications provided an augmented transduction of AI-ameloblasts, revealed following vector dose normalization in A549 cells with a superior effect (up to 404-fold) of pK7/RGD double modification. This robust infectivity enhancement occurred through vector binding to both αvβ3/αvβ5 integrins and heparan sulfate proteoglycans (HSPGs) highly expressed by AI-ameloblasts as revealed by gene transfer blocking experiments. This work thus not only pioneers establishment of human AI ameloblast-like cell population as a model for in vitro studies but also reveals an optimal infectivity-enhancement strategy for a potential Ad5 vector-mediated gene therapy for AI