Anti-angiogenic potential of VEGF blocker dendron-laden gellan gum hydrogels for tissue engineering applications

Damage of non-vascularised tissues such as cartilage and cornea can result in healing processes accompanied by a non-physiological angiogenesis. Peptidic aptamers have recently been reported to block the vascular endothelial growth factor (VEGF). However, the therapeutic applications of these aptamers is limited due to their short half-life in vivo. In this work, an enhanced stability and bioavailability of a known VEGF blocker aptamer sequence (WHLPFKC) was pursued through its tethering of molecular scaffolds based on hyperbranched peptides, the poly(É -lysine) dendrons, bearing three branching generations. The proposed design allowed simultaneous and orderly-spaced exposure of sixteen aptamers per dendrimer to the surrounding biological microenvironent, as well as a relatively hydrophobic core based on di-phenylalanine aiming to promote an hydrophobic interaction with the hydrophobic moieties of ionically-crosslinked metacrylated gellan gum (iGG-MA) hydrogels. The VEGF blocker dendrons were entrapped in iGG-MA hydrogels and their capacity to prevent endothelial cell sprouting was assessed qualitatively and quantitatively using 3D in vitro models and the in vivo chick chorioallantoic membrane (CAM) assay. The data demonstrate that at nanoscale concentrations, the dendronised structures were able to enhance control of the biological actvity of WHLPFKC at the material/tissue interface and hence the anti-angiogenic capacity of iGG-MA hydrogels not only preventing blood vessel invasion, but also inducing their regression at the tissue/iGG-MA interface. The in ovo study confirmed that iGG-MA functionalised with the dendron VEGF blockers do inhibit angiogenesis by controlling both size and ramifications of blood vessels in proximity of the implanted gel surface.This work was mainly supported by the EC FP7 project Disc Regeneration (Contract No NMP3-LA-2008-213904). This study was also funded by the EC FP7 Programme contract agreement no REGPOT-CT2012-316331-POLARIS

Feasibility randomized-controlled trial of online acceptance and commitment therapy for painful peripheral neuropathy in people living with HIV: The OPEN study

Background Neuropathic pain negatively affects quality of life among people living with HIV (PLWH). This study examined the feasibility of conducting a full‐scale randomized‐controlled trial of online acceptance and commitment therapy (“ACT OPEN”) for neuropathic pain in PLWH. Methods Using a parallel‐groups design, thirty‐eight participants were randomized to ACT OPEN or a waitlist control (2:1). Participants completed standard self‐report outcome measures at baseline, and two‐ and five‐months post‐randomization. Participants were aware of their allocation, but assessment was blinded. Results Twenty‐five participants were randomized to ACT OPEN and 13 to the control (of 133 referrals). ACT OPEN completion was 69% and two‐month trial retention was 82%. Treatment credibility and satisfaction scores for ACT OPEN were comparable to scores reported in previous trials of cognitive‐behavioural treatments for pain. Four adverse events were reported during the study, including one serious adverse event; all of these were unrelated to the research procedures. Small to moderate effects and 95% confidence intervals suggest that the true effect may favour ACT OPEN for improvements in pain intensity/interference and depression. Conclusions A full‐scale RCT of online ACT for pain management in PLWH may be feasible with refinements to trial design to facilitate recruitment. Significance Research on pain management in people living with HIV has primarily focused on pharmacological treatments with limited success. This is the first study to show the potential feasibility of a psychological treatment based on acceptance and commitment therapy delivered online and tailored for pain management in people with HIV (“ACT OPEN”). ACT OPEN may be a promising treatment in this population and further evaluation in a full‐scale randomized‐controlled trial appears warranted. Trial Registration: The trial was registered (clinicaltrials.gov; NCT03584412)

Connecting the Dots: Responses of Coastal Ecosystems to Changing Nutrient Concentrations

Empirical relationships between phytoplankton biomass and nutrient concentrations established across a wide range of different ecosystems constitute fundamental quantitative tools for predicting effects of nutrient management plans. Nutrient management plans based on such relationships, mostly established over trends of increasing rather than decreasing nutrient concentrations, assume full reversibility of coastal eutrophication. Monitoring data from 28 ecosystems located in four well-studied regions were analyzed to study the generality of chlorophyll a versus nutrient relationships and their applicability for ecosystem management. We demonstrate significant differences across regions as well as between specific coastal ecosystems within regions in the response of chlorophyll a to changing nitrogen concentrations. We also show that the chlorophyll a versus nitrogen relationships over time constitute convoluted trajectories rather than simple unique relationships. The ratio of chlorophyll a to total nitrogen almost doubled over the last 30-40 years across all regions. The uniformity of these trends, or shifting baselines, suggest they may result from large-scale changes, possibly associated with global climate change and increasing human stress on coastal ecosystems. Ecosystem management must, therefore, develop adaptation strategies to face shifting baselines and maintain ecosystem services at a sustainable level rather than striving to restore an ecosystem state of the past. © 2011 American Chemical Society.This research is a contribution to the Thresholds Integrated Project (contract FP6-003933-2) and WISER (contract FP7-226273), funded by the European Commission.Peer Reviewe

Effects of Total Resources, Resource Ratios, and Species Richness on Algal Productivity and Evenness at Both Metacommunity and Local Scales

The study of the interrelationship between productivity and biodiversity is a major research field in ecology. Theory predicts that if essential resources are heterogeneously distributed across a metacommunity, single species may dominate productivity in individual metacommunity patches, but a mixture of species will maximize productivity across the whole metacommunity. It also predicts that a balanced supply of resources within local patches should favor species coexistence, whereas resource imbalance would favor the dominance of one species. We performed an experiment with five freshwater algal species to study the effects of total supply of resources, their ratios, and species richness on biovolume production and evenness at the scale of both local patches and metacommunities. Generally, algal biovolume increased, whereas algal resource use efficiency (RUE) and evenness decreased with increasing total supply of resources in mixed communities containing all five species. In contrast to predictions for biovolume production, the species mixtures did not outperform all monocultures at the scale of metacommunities. In other words, we observed no general transgressive overyielding. However, RUE was always higher in mixtures than predicted from monocultures, and analyses indicate that resource partitioning or facilitation in mixtures resulted in higher-than-expected productivity at high resource supply. Contrasting our predictions for the local scale, balanced supply of resources did not generally favor higher local evenness, however lowest evenness was confined to patches with the most imbalanced supply. Thus, our study provides mixed support for recent theoretical advancements to understand biodiversity-productivity relationships

Faecal immunochemical tests (FIT) can help to rule out colorectal cancer in patients presenting in primary care with lower abdominal symptoms:a systematic review conducted to inform new NICE DG30 diagnostic guidance

__Background:__ This study has attempted to assess the effectiveness of quantitative faecal immunochemical tests (FIT) for triage of people presenting with lower abdominal symptoms, where a referral to secondary care for investigation of suspected colorectal cancer (CRC) is being considered, particularly when the 2-week criteria are not met. __Methods:__ We conducted a systematic review following published guidelines for systematic reviews of diagnostic tests. Twenty-one resources were searched up until March 2016. Summary estimates were calculated using a bivariate model or a random-effects logistic regression model. __Results:__ Nine studies are included in this review. One additional study, included in our systematic review, was provided as 'academic in confidence' and cannot be described herein. When FIT was based on a single faecal sample and a cut-off of 10 μg Hb/g faeces, sensitivity estimates indicated that a negative result using either the OC-Sensor or HM-JACKarc may be adequate to rule out nearly all CRC; the summary estimate of sensitivity for the OC-Sensor was 92.1%, based on four studies, and the only study of HM-JACKarc to assess the 10 μg Hb/g faeces cut-off reported a sensitivity of 100%. The corresponding specificity estimates were 85.8% (95% CI 78.3-91.0%) and 76.6%, respectively. When the diagnostic criterion was changed to include lower grades of neoplasia, i.e. the target condition included higher risk adenoma (HRA) as well as CRC, the rule-out performance of both FIT assays was reduced. __Conclusions:__ There is evidence to suggest that triage using FIT at a cut-off around 10 μg Hb/g faeces has the potential to correctly rule out CRC and avoid colonoscopy in 75-80% of symptomatic patients. Systematic review registration: PROSPERO 4201603772

Dome patterns in pelagic size spectra reveal strong trophic cascades

In ecological communities, especially the pelagic zones of aquatic ecosystems, certain bodysize ranges are often over-represented compared to others. Community size spectra, the distributions of community biomass over the logarithmic body-mass axis, tend to exhibit regularly spaced local maxima, called "domes", separated by steep troughs. Contrasting established theory, we explain these dome patterns as manifestations of top-down trophic cascades along aquatic food chains. Compiling high quality size-spectrum data and comparing these with a size-spectrum model introduced in this study, we test this theory and develop a detailed picture of the mechanisms by which bottom-up and top-down effects interact to generate dome patterns. Results imply that strong top-down trophic cascades are common in freshwater communities, much more than hitherto demonstrated, and may arise in nutrient rich marine systems as well. Transferring insights from the general theory of nonlinear pattern formation to domes patterns, we provide new interpretations of past lake-manipulation experiments