Oral Supplementation with Algal Sulphated Polysaccharide in Subjects with Inflammatory Skin Conditions: A Randomised Double-Blind Placebo-Controlled Trial and Baseline Dietary Differences.

We examined the effect of a dietary seaweed extract-sulfated xylorhamnoglucuronan (SXRG84)-on individuals with inflammatory skin conditions. A subgroup analysis of a larger trial was undertaken, where 44 participants with skin conditions were enrolled in a double-blind placebo-controlled crossover design. Subjects ingested either SXRG84 extract (2 g/day) for six weeks and placebo for six weeks, or vice versa. At baseline, six- and twelve-weeks inflammatory markers and the gut microbiota were assessed, as well as skin assessments using the dermatology quality of life index (DQLI), psoriasis area severity index (PASI) and visual analogue scales (VAS). There were significant differences at weeks six and twelve for pro-inflammatory cytokines IFN-γ (p = 0.041), IL-1ß (p = 0.030), TNF-α (p = 0.008) and the anti-inflammatory cytokine IL-10 (p = 0.026), determined by ANCOVA. These cytokines were all significantly higher at six weeks post placebo compared to twelve weeks post placebo followed by SXRG84 treatment. A total of 23% of participants reported skin improvements, as measured by VAS (mean difference 3.1, p = 0.0005) and the DQLI score (mean difference -2.0, p = 0.049), compared to the 'non-responders'. Thus, the ingestion of SXRG84 for 6 weeks reduced inflammatory cytokines, and a subset of participants saw improvements.

Improved Plasma Lipids, Anti-Inflammatory Activity, and Microbiome Shifts in Overweight Participants: Two Clinical Studies on Oral Supplementation with Algal Sulfated Polysaccharide.

Seaweed polysaccharides in the diet may influence both inflammation and the gut microbiome. Here we describe two clinical studies with an Ulva sp. 84-derived sulfated polysaccharide­"xylorhamnoglucuronan" (SXRG84)­on metabolic markers, inflammation, and gut flora composition. The first study was a double-blind, randomized placebo-controlled trial with placebo, and either 2 g/day or 4 g/day of SXRG84 daily for six weeks in 64 overweight or obese participants (median age 55 years, median body mass index (BMI) 29 kg/m2). The second study was a randomized double-blind placebo-controlled crossover trial with 64 participants (median BMI 29 kg/m2, average age 52) on placebo for six weeks and then 2 g/day of SXRG84 treatment for six weeks, or vice versa. In Study 1, the 2 g/day dose exhibited a significant reduction in non-HDL (high-density lipoprotein) cholesterol (−10% or −0.37 mmol/L, p = 0.02) and in the atherogenic index (−50%, p = 0.05), and two-hour insulin (−12% or −4.83 mU/L) showed trends for reduction in overweight participants. CRP (C-reactive protein) was significantly reduced (−27% or −0.78 mg/L, p = 0.03) with the 4 g/day dose in overweight participants. Significant gut flora shifts included increases in Bifidobacteria, Akkermansia, Pseudobutyrivibrio, and Clostridium and a decrease in Bilophila. In Study 2, no significant differences in lipid measures were observed, but inflammatory cytokines were improved. At twelve weeks after the SXRG84 treatment, plasma cytokine concentrations were significantly lower than at six weeks post placebo for IFN-γ (3.4 vs. 7.3 pg/mL), IL-1ß (16.2 vs. 23.2 pg/mL), TNF-α (9.3 vs. 12.6 pg/mL), and IL-10 (1.6 vs. 2.1 pg/mL) (p < 0.05). Gut microbiota abundance and composition did not significantly differ between groups (p > 0.05). Together, the studies illustrate improvements in plasma lipids and an anti-inflammatory effect of dietary SXRG84 that is participant specific.

The effect of omega-3 long chain polyunsaturated fatty acids on aggressive behaviour in adult male prisoners: a structured study protocol for a multi-centre, double-blind, randomised placebo-controlled trial and translation into policy and practice.

BACKGROUND: Interventions to better manage aggressive behaviour and reduce recidivism are a primary concern for corrective services. Nutritional interventions to correct prisoner behaviour have been largely overlooked in the literature. Emerging evidence suggests that dietary intake influences aggressive behaviours and that nutritional supplementation with omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) could attenuate both the severity and frequency of aggressive behaviour. METHODS: Adult male prisoners who have a history of aggressive behaviour (n = 600) will be recruited from at least 6 Correctional Centres and randomised to receive either n-3 LCPUFA or placebo supplementation for a 16-week duration. Treatment will be with either 1 g/day of n-3 LCPUFA (694 mg DHA and 397 mg EPA) or placebo capsules, which are a corn/soy oil blend and are identical in size and colour. The primary outcome measure is the Inmate Behavioural Observation Scale (IBOS): an objective measure of aggressive behaviour. Secondary outcome measures include questionnaires (including aggression, attention deficit disorder, impulsivity, depression/anxiety/stress scales), engagement in programmes, recidivism and quality of life. Baseline and post-intervention assessments include the IBOS, questionnaires and blood to measure the levels of n-3 LCPUFA. DISCUSSION: To conclusively test the potential that increasing n-3 LCPUFA intakes can improve rates of prisoner aggression and associated mental health and violence-related social system management costs, we propose an adequately powered multi-centre, double-blind, randomised controlled trial, examining the effects of n-3 LCPUFA supplementation on aggressive behaviour in adult male prisoners. If successful, this study will inform prisoner policy with respect to nutrition and by inference contribute to a broader community approach to preventative mental health practices. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN12618001665224 . Registered on 10 October 2018.

Fibrinogen, collagen, and transferrin adsorption to poly(3,4-ethylenedioxythiophene)-xylorhamno-uronic glycan composite conducting polymer biomaterials for wound healing applications.

We present the conducting polymer poly (3,4-ethylenedioxythiophene) (PEDOT) doped with an algal-derived glycan extract, Phycotrix™ [xylorhamno-uronic glycan (XRU84)], as an innovative electrically conductive material capable of providing beneficial biological and electrical cues for the promotion of favorable wound healing processes. Increased loading of the algal XRU84 into PEDOT resulted in a reduced surface nanoroughness and interfacial surface area and an increased static water contact angle. PEDOT-XRU84 films demonstrated good electrical stability and charge storage capacity and a reduced impedance relative to the control gold electrode. A quartz crystal microbalance with dissipation monitoring study of protein adsorption (transferrin, fibrinogen, and collagen) showed that collagen adsorption increased significantly with increased XRU84 loading, while transferrin adsorption was significantly reduced. The viscoelastic properties of adsorbed protein, characterized using the ΔD/Δf ratio, showed that for transferrin and fibrinogen, a rigid, dehydrated layer was formed at low XRU84 loadings. Cell studies using human dermal fibroblasts demonstrated excellent cell viability, with fluorescent staining of the cell cytoskeleton illustrating all polymers to present excellent cell adhesion and spreading after 24 h.

3D bioprinting dermal-like structures using species-specific ulvan.

3D bioprinting has been increasingly employed in skin tissue engineering for manufacturing living constructs with three-dimensional spatial precision and controlled architecture. There is however, a bottleneck in the tunability of bioinks to address specific biocompatibility challenges, functional traits and printability. Here we report on a traditional gelatin methacryloyl (GelMA) based bioink, tuned by addition of an ulvan type polysaccharide, isolated from a cultivated source of a specific Australian Ulvacean macroalgae (Ul84). Ul84 is a sulfate- and rhamnose-rich polysaccharide, resembling mammalian glycosaminoglycans that are involved in wound healing and tissue matrix structure and function. Printable bioinks were developed by addition of methacrylated Ul84 (UlMA) to GelMA solutions. The inclusion of UlMA in the bioinks facilitated the extrusion printing process by reducing yield stress. The resultant printed structures containing ulvan exhibited improved mechanical strength and regulated the rate of scaffold degradation. The 3D printed cell-laden structures with human dermal fibroblasts demonstrated high cell viability, support of cell proliferation and dermal-like properties as evidenced by the deposition of key dermal extracellular matrix components including collagen I, collagen III, elastin and fibronectin. In vitro degradation suggested the role of UlMA in supporting structural stability of the printed cellular structures. Taken together, the present work demonstrates progression towards a biocompatible and biofunctional ink that simultaneously delivers improved mechanical, structural and stability traits that are important in facilitating real world applications in skin tissue repair.

The Effect of Dietary Supplementation on Aggressive Behaviour in Australian Adult Male Prisoners: A Feasibility and Pilot Study for a Randomised, Double Blind Placebo Controlled Trial.

This study aimed to assess the feasibility of conducting a nutrition trial in adult male prisoners. Adult male prisoners were recruited for a 16-week randomised control trial comparing the effect of ingestion of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) and multivitamin supplements versus placebo on aggressive behaviour. The baseline and post-intervention assessments from the participant blood samples were the erythrocyte n-3 LCPUFA levels as well as measures of aggressive behaviour determined through institutional records of misconduct (IRM), the Inmate Behaviour Observation Scale (IBOS), and questionnaires. A total of 136 adult male prisoners consented to the study with a retention rate of 60%, and 93% of blood samples were successfully collected. The IRM and IBOS scores were collected for 100% of participants, whilst 82-97% of participants completed the questionnaires. From the baseline data, the Odds Ratio shows that prisoners are 4.3 times more likely to have an IBOS >2 if they are below the 6% cut off on the omega-3 index. Both groups improved across all outcome measures and, at the current sample size, no significant differences were seen between them. A power calculation suggests a total sample size of 600 participants is required to detect the effects of this dietary supplementation, and that this supplementation study is feasible in a Correctional Centre. Important criteria for the exclusion and consideration of logistics and compliance are presented.

Development of rhamnose-rich hydrogels based on sulfated xylorhamno-uronic acid toward wound healing applications.

An array of biological properties is demonstrated in the category of extracts broadly known as ulvans, including antibacterial, anti-inflammatory and anti-coagulant activities. However, the development of this category in biomedical applications is limited due to high structural variability across species and a lack of consistent and scalable sources. In addition, the modification and formulation of these molecules is still in its infancy with regard to progressing to product development. Here, a sulfated and rhamnose-rich, xylorhamno-uronic acid (XRU) extract from the cell wall of a controlled source of cultivated Australian ulvacean macroalgae resembles mammalian connective glycosaminoglycans. It is therefore a strong candidate for applications in wound healing and tissue regeneration. This study targets the development of polysaccharide modification for fabrication of 3D scaffolds for skin cell (fibroblast) culture. The XRU extract is methacrylated and UV-crosslinked to produce hydrogels with tuneable mechanical properties. The hydrogels demonstrate high cell viability and support cell proliferation over 14 days, which are far more functional than comparable alginate gels. Importantly, an XRU-based bioink is developed for extrusion printing 3D constructs both with and without cell encapsulation. These results highlight the close to product potential of this rhamnose-rich XRU extract as a promising biomaterial toward wound healing. Future studies should be focused on in-depth in vitro characterizations to examine the role of the material in dermal extracellular matrix (ECM) secretion of 3D printed structures, and in vivo characterizations to assess its capacity in supporting wound healing.

Correction: Baseline Omega-3 Index Correlates with Aggressive and Attention Deficit Disorder Behaviours in Adult Prisoners.

[This corrects the article DOI: 10.1371/journal.pone.0120220.].

Fabrication and In Vitro Characterization of Electrochemically Compacted Collagen/Sulfated Xylorhamnoglycuronan Matrix for Wound Healing Applications.

Skin autografts are in great demand due to injuries and disease, but there are challenges using live tissue sources, and synthetic tissue is still in its infancy. In this study, an electrocompaction method was applied to fabricate the densely packed and highly ordered collagen/sulfated xylorhamnoglycuronan (SXRGlu) scaffold which closely mimicked the major structure and components in natural skin tissue. The fabricated electrocompacted collagen/SXRGlu matrices (ECLCU) were characterized in terms of micromorphology, mechanical property, water uptake ability and degradability. The viability, proliferation and morphology of human dermal fibroblasts (HDFs) cells on the fabricated matrices were also evaluated. The results indicated that the electrocompaction process could promote HDFs proliferation and SXRGlu could improve the water uptake ability and matrices' stability against collagenase degradation, and support fibroblast spreading on the ECLCU matrices. Therefore, all these results suggest that the electrocompacted collagen/SXRGlu scaffold is a potential candidate as a dermal substitute with enhanced biostability and biocompatibility.

Parameters affecting the analytical profile of fatty acids in the macroalgal genus Ulva.

The fatty acids (FA) of Ulva have potential to contribute to nutrition. However the large variability of FA profiles of Ulva species; thus the quality and quantity of FA in relation to nutrition is poorly defined. Herein we investigate the FA profile of 74 cultured Ulva samples crossing five culture regimes, six extraction regimes and four post-harvesting processes. This is compared alongside a comprehensive review of FA profiles of Ulva spp. With regard to the literature, Ulva is characterised by C16:0 (30.5±11.5%), C18:3 n-3 (14.5±6.3%), C18:4 n-3 (12.5±5.4%), C16:4 n-3 (8.9±4.8%) and C18:1 n-7 (10.1±4.0%). The investigated Ulva fell within the reported range of specific FA. High nutrient conditions showed the most desirable FA profile for health, along with the highest total FA content (56mgg(-1) dry weight equivalent) when extracted with an optimised protocol.

Applications of seaweed extracts in Australian agriculture: past, present and future.

A rapidly growing world population has highlighted the need to significantly increase food production in the context of a world with accelerating soil and water shortages as well as climatic stressors. This situation has generated new interest in the application of liquid seaweed extracts because of their potent plant growth-enhancing properties through metabolic benefits, triggering disease response pathways and increasing stress tolerance. The basis for these benefits is complex and poorly understood. Liquid seaweed extracts are complex and have been demonstrated to possess novel mechanisms for increasing crop productivity. The benefits of seaweed extracts to crops have previously been reviewed in the context of the northern hemisphere, but not in the context of Australia, its crops and unique stressors. This review considers the application of seaweed extracts in Australian agriculture by (i) introducing the history of the Australian liquid seaweed extract industry and (ii) focusing on evidence of Australian research related to seaweed extract composition, plant growth properties during plant establishment, pathogenic disease and new approaches to phenotyping the biological efficacy of seaweed extracts. This type of research is essential for future Australian agriculture to develop effective strategies for the use of liquid seaweed extracts.

Baseline omega-3 index correlates with aggressive and attention deficit disorder behaviours in adult prisoners.

BACKGROUND: There is emerging evidence that the supplementation of omega-3 contributes to a decrease in aggressive behaviour in prison populations. A challenge of such research is achieving statistical power against effect sizes which may be affected by the baseline omega-3 index. There are no published data on the blood omega-3 index with studies of this kind to assess the variability of the blood omega-3 index in conjunction with aggression and attention deficit assessments. OBJECTIVE: To determine if the variance of the omega-3 index is correlated with aggressive and attention deficit behaviour in a prison population. DESIGN: 136 adult male prisoners were recruited from South Coast Correctional Centre (SCCC), NSW Australia. A 7 point categorisation was used to quantify levels of aggressive behaviour (4 weeks) from individual SCCC case notes, whereby higher scores correspond to increasingly aggressive behaviour. Study participants completed the Aggression Questionnaire (AQ) and the Brown's Attention Deficit Disorder Scales (BADDS), provided a blood sample for erythrocyte fatty acid analysis using gas chromatography and the omega-3 index was calculated. RESULTS: The baseline omega-3 index ranged from 2.3% to 10.3%, indicating that some participants already had substantial omega-3 intake, however a median of 4.7% indicated a lower overall omega-3 intake than the general Australian population. Assessment of aggressive and attention deficit behaviour shows that there were negative correlations between baseline omega-3 index and baseline aggression categorisation scores (r = -0.21, P = 0.016); total AQ score (r = -0.234, P = 0.011); Anger (r = -0.222 p = 0.016); Hostility AQ (r = -0.239, P = 0.009); indirect aggression (r = -0.188 p = 0.042); total BADDS (r = -0.263, p = 0.005); Activation (r = -0.224, p = 0.016); Attention (r = -0.192, p = 0.043); Effort (r = -0.253, p = 0.007); Affect (r = -0.330, p = 0.000) and Memory (r = -0.240, p = 0.010). CONCLUSIONS: There is a high variability in omega-3 status of a NSW prison population, and inmates with lower omega-3 index were more aggressive and had higher ADD scores.

A Molecular Survey of Ulva (Chlorophyta) in Temperate Australia Reveals Enhanced Levels of Cosmopolitanism.

The green algal genus Ulva includes a speciose group of marine macroalgae inhabiting shallow seas worldwide. Although algal blooms in Asia highlight the opportunistic nature of several "nuisance" species, recent research clearly reveals important positive benefits of Ulva. Applied research requires accurate, reliable, and rapid identification, however, identification of Ulva spp. has met with con-siderable difficulty. Consequently, many have turned to molecular markers to aid in taxonomy. Previous studies of plants and algae have relied heavily on ITS and rbcL. Recently, tufA has been presented as a suitable barcoding gene to facilitate species-level identification of green macroalgae and it is used here to explore the diversity of Ulva spp. in temperate Australia. Ninety Ulva specimens collected from 38 sites across five states were sequenced for this gene region with exemplars from each genetic group also sequenced for rbcL to test for congruence. Collections of Australian Ulva spp. were compared to samples from Asia and North America and exhibited trends consistent with recent studies in terms of species relationships. Results support an overwhelmingly cosmopolitan flora in temperate Australia that contrasts with other Australasian surveys of Ulva that report a greater number of endemics and new species. Four new records, as well as numerous range extensions for taxa already known from the country, are documented. Evidence for three nonindigenous Ulva species in temperate Australia is discussed.