Exome-informed formulations of food proteins enhance body growth and feed conversion efficiency in ad libitum-fed mice.

Meeting requirements for dietary proteins, especially of essential amino acids (EAAs), is critical for the life-long health of living organisms. However, defining EAA targets for preparing biologically-matched nutrition that satisfies metabolic requirements for protein remains challenging. Previous research has shown the advantages of 'exome matching' in representing the specific requirement of dietary AAs, where the target dietary AA profile was derived from in silico translation of the genome of an organism, specifically responsible for protein expression (the 'exome'). However, past studies have assessed these effects in only one sex, for few parameters (body mass and composition), and have used purified diets in which protein is supplied as a mixture of individual AAs. Here, for the first time, we utilise a computational method to guide the formulation of custom protein blends and test if exome matching can be achieved at the intact protein level, through blending standard protein ingredients, ultimately leading to optimal growth, longevity and reproductive function. Mice were provided ad libitum (ad lib) access to one of the four iso-energetic protein-limited diets, two matched and two mis-matched to the mouse exome target, and fed at a fixed protein energy level of 6.2%. During or following 13-weeks of feeding, the food intake, body growth, composition and reproductive functions were measured. Compared to the two mis-matched diets, male and female animals on the exome-matched diet with protein digestibility correction applied, exhibited significantly improved growth rates and final body mass. The feed conversion efficiency in the same diet was also increased by 62% and 40% over the worst diets for males and females, respectively. Male, not female, exhibited higher accretion of lean body mass with the matched, digestibility-corrected diet. All reproductive function measures in both sexes were comparable among diets, with the exception of testicular daily sperm production in males, which was higher in the two matched diets versus the mis-matched diets. The results collectively demonstrate the pronounced advantages of exome-matching in supporting body growth and improving feed conversion efficiency in both sexes. However, the potential impact of this approach in enhancing fertility needs further investigation.

Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis.

INTRODUCTION: Psoriatic arthritis (PsA) affects around 150 000 people in the UK of whom around 50% require treatment with biologics. The most used biologics for PsA target tumour necrosis factor (TNF) or interleukin-17A (IL-17A). About 50% of patients respond to each, but it is not currently possible to predict response for individual patients, necessitating sequential treatment steps. A recent proof of concept study in PsA suggested that using peripheral immunophenotype to choose therapy could improve time to treatment response.This study will test the hypothesis, within an open-label parallel-group biomarker-stratified multicentre randomised controlled trial, which the baseline proportion of CD4+T cells with an activated type 17 immunophenotype (Th17 levels) predicts response to IL-17A or TNF inhibitors in PsA. Additional analyses will identify if the model can be refined by combining additional clinical and immunophenotypic factors. Statistical modelling will be used to predict the likely effectiveness of these approaches compared with standard care. METHODS AND ANALYSIS: Patients with PsA eligible to start their first biologic as part of standard care are recruited and baseline blood tests are taken for immunophenotyping. Participants are stratified equally by Th17 levels and randomised 1:1 to receive either TNF (adalimumab) or IL-17A (secukinumab) inhibitors. The primary analysis will establish the interaction between baseline immunophenotype and treatment on the primary outcome (achievement of minimal disease activity criteria at week 24). In secondary analysis, modelling will identify if this prediction model can be optimised further by incorporating clinical phenotypes and additional immunophenotyping techniques. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the North West Preston Research Ethics Committee (ref 21/NW/0016). Dissemination will be via conference presentations and peer-reviewed publications, aiming to impact on treatment guidelines. TRIAL REGISTRATION NUMBER: ISRCTN17228602.

Comparative yields of antimicrobial peptides released from human and cow milk proteins under infant digestion conditions predicted by in silico methodology.

Mammalian milk proteins are known to encrypt antimicrobial peptides (AMPs) which can be passively released and exert bioactivity in the gastrointestinal and cardiovascular systems pre- or post-absorption, respectively. However, the contribution of 'passive' food-derived AMPs to the pool of endogenous and microbial AMPs has not been differentiated in previous research. Insight into the consequences of protein digestion and peptide bioactivity can be gained using in silico tools. The aim of this investigation was to use in silico methods to characterise the yields of AMPs released from major proteins in human and cow milk under infant digestion conditions, as relevant to early nutrition. The profiles of major proteins in human and cow milk from UniProtKB/Swiss-Prot, were subjected to in silico digestion by ExPASy-PeptideCutter, and the AMP activity of resulting peptides (≥4 amino acids, AAs) evaluated with the CAMPR3-RF predictive tool. The mass yields and counts of absorbing (≤10 AAs) and non-absorbing (>10 AAs) AMPs, as found in human, cow and 'humanised' ratios of cow milk proteins, were quantified. The results indicated that major whey proteins from both human and cow milks displayed a higher degree of hydrolysis than caseins, consistent with their known 'fast' digestion properties. Larger albumin and lactoferrin proteins generated relatively more and/or longer peptides. Yields of AMPs from cow milk were higher than from human milk, even after standardising the ratio of whey to casein and total protein concentration, as practiced in formulations manufactured for human newborn babies. Whereas alpha-lactalbumin (2.65 g L-1) and lactoferrin (1.75 g L-1) provided the major yields of AMPs in human milk whey proteins; beta-lactoglobulin, which is unique to cow milk, released the highest yield of AMPs in cow milk (3.25 g L-1 or 19.9% w/w of total whey protein), which may represent an important and overlooked biological function of this protein in cow milk.

Demonstrating a link between diet, gut microbiota and brain: 14C radioactivity identified in the brain following gut microbial fermentation of 14C-radiolabeled tyrosine in a pig model.

Background: There is a need to better understand the relationship between the diet, the gut microbiota and mental health. Metabolites produced when the human gut microbiota metabolize amino acids may enter the bloodstream and have systemic effects. We hypothesize that fermentation of amino acids by a resistant protein-primed gut microbiota could yield potentially toxic metabolites and disturb the availability of neurotransmitter precursors to the brain. However, these mechanisms are challenging to investigate via typical in vitro and clinical methods. Methods: We developed a novel workflow using 14C radiolabeling to investigate complex nutrient-disease relationships. The first three steps of the workflow are reported here. α-Linolenic acid (ALA) was used as a model nutrient to confirm the efficacy of the workflow, and tyrosine (Tyr) was the test nutrient. 14C-Tyr was administered to male weanling pigs fed a high resistant protein diet, which primed the gut microbiota for fermenting protein. The hypotheses were; (1) that expected biodistribution of 14C-ALA would be observed, and (2) that radioactivity from 14C-Tyr, representing Tyr and other amino acids released from resistant protein following gut microbial fermentation, would be bioavailable to the brain. Results: Radioactivity from the 14C-ALA was detected in tissues reflecting normal utilization of this essential fatty acid. Radioactivity from the 14C-Tyr was detected in the brain (0.15% of original dose). Conclusion: Metabolites of gut-fermented protein and specifically amino acid precursors to neurotransmitters such as tyrosine, are potentially able to affect brain function. By extension, resistant proteins in the diet reaching the gut microbiota, also have potential to release metabolites that can potentially affect brain function. The high specificity of detection of 14C radioactivity demonstrates that the proposed workflow can similarly be applied to understand other key diet and health paradigms.

Production of hydrogen peroxide in commercial orange juice products is related to proximate composition, processing conditions and storage time.

Based on the observed production of H2O2 in formulated beverages containing artificial or 'non-natural' mixtures of anti-oxidants (AOXs), it was hypothesized that the natural redox-active compounds present in orange juice (OJ) might also produce H2O2. Here, we report the levels of H2O2 found in commercially manufactured OJ products in 'fresh' (4 °C on-shelf storage, N = 9) and 'processed' (ambient on-shelf storage, N = 9) categories. The average concentrations of H2O2 immediately after opening the container (T0) were significantly higher (p < 0.01) in processed (11.15 ± 2.83 µM) versus fresh (3.74 ± 2.02 µM) sample sets. Levels of H2O2 at T0 were uncorrelated with storage time post-manufacture and increased after opening (1 to 4-fold), followed by significant decrease after 24 hr (p < 0.05). Using Pearson's correlation analysis; ascorbic acid, total reducible substances and total sugar were each significantly positively correlated, while total protein, fibre and unsaturated fats were each significantly negatively correlated, with H2O2 levels in OJs.

Demonstration of anti-oxidant properties of mustard seed (Brassica juncea) protein isolate in orange juice.

Previous research has shown that formulated and natural beverages containing mixtures of anti-oxidants can produce stable levels of hydrogen peroxide (H2O2). The aim of this study was to demonstrate the ultimate anti-oxidant effects of proteins for suppressing H2O2, using a protein extract from mustard seed (Brassica juncea). The mustard seed protein isolate (MPI) contained âˆ¼51% protein, and 6.4 mg GAe/g TS of total reducible substances, presumably representing secondary metabolites, including polyphenolics. Dose-dependent suppression of H2O2 (present at 110 µM and 550 µM), in fresh and thermally-processed orange juice was complete in the presence of 0.1 mg/mL MPI after 24 hr, with slightly higher anti-oxidant efficacy than the fruit juice-derived reference protein, thaumatin. The combination of thiol-rich amino acid (methionine and cysteine)-containing proteins and other anti-oxidant species in the MPI were highly effective for inhibiting autoxidation-mediated production of H2O2 in orange juice, and may be useful for other manufactured beverages.

Reduced Growth, Altered Gut Microbiome and Metabolite Profile, and Increased Chronic Kidney Disease Risk in Young Pigs Consuming a Diet Containing Highly Resistant Protein.

High-heat processed foods contain proteins that are partially resistant to enzymatic digestion and pass through to the colon. The fermentation of resistant proteins by gut microbes produces products that may contribute to chronic disease risk. This pilot study examined the effects of a resistant protein diet on growth, fecal microbiome, protein fermentation metabolites, and the biomarkers of health status in pigs as a model of human digestion and metabolism. Weanling pigs were fed with standard or resistant protein diets for 4 weeks. The resistant protein, approximately half as digestible as the standard protein, was designed to enter the colon for microbial fermentation. Fecal and blood samples were collected to assess the microbiome and circulating metabolites and biomarkers. The resistant protein diet group consumed less feed and grew to ~50% of the body mass of the standard diet group. The diets had unique effects on the fecal microbiome, as demonstrated by clustering in the principal coordinate analysis. There were 121 taxa that were significantly different between groups (adjusted-p < 0.05). Compared with control, plasma tri-methylamine-N-oxide, homocysteine, neopterin, and tyrosine were increased and plasma acetic acid was lowered following the resistant protein diet (all p < 0.05). Compared with control, estimated glomerular filtration rate (p < 0.01) and liver function marker aspartate aminotransferase (p < 0.05) were also lower following the resistant protein diet. A resistant protein diet shifted the composition of the fecal microbiome. The microbial fermentation of resistant protein affected the levels of circulating metabolites and the biomarkers of health status toward a profile indicative of increased inflammation and the risk of chronic kidney disease.

Formulations of selected Energy beverages promote pro-oxidant effects of ascorbic acid and long-term stability of hydrogen peroxide.

Recently, autoxidation mediated by ascorbic acid (AA) and other ingredients, has been implicated in generation of hydrogen peroxide (H2O2) in so-called Energy beverages. Here, we report the use of cyclic voltammetry and the FOX assay to monitor at short and long incubation times, respectively, the production and stability of H2O2 generated by AA and redox-active ingredients. Levels of H2O2 in Energy drinks (36.5 ± 4.0 µM at 4 °C and 64.2 ± 7.6 µM at 20 °C) were found to be stable or increased (p < 0.05) upon vessel opening. A predictive model for the production of H2O2 as a function of AA concentration, temperature and incubation time, and depending on ingredients present, indicated that H2O2 peaked at 91-726 µM after 1 day and declined to âˆ¼ 42-60 µM (4 °C) or zero after âˆ¼10 days. The research supports that levels of H2O2 in beverages containing anti-oxidant mixtures and dissolved oxygen should be monitored and formulations modified to avoid AA autoxidation.

Relaxation Effects of Essential Oils Are Explained by Their Interactions with Human Brain Neurotransmitter Receptors and Electroencephalography Rhythms.

Inhaled essential oils (EOs) are bioavailable to the brain and are consistently reported to promote relaxation effects. Their mechanisms of action are however not well understood. The aim of this investigation was to assess the neuroactivity of EOs based on their (i) binding interactions to neurotransmitter receptors and (ii) bioelectrical activities in the brain as measured by electroencephalography (EEG). These EO properties were compared to those of reference pharmaceutical compounds with effects also measured by EEG. Relative receptor binding efficacies of 10 reference compounds, 180 EOs, and 9 EO extracts with 7 different neurotransmitter receptors were calculated using in silico molecular docking procedures. Changes in brain EEG rhythms, as standardized changes in absolute power, were determined for the reference compounds and selected EOs and compared to receptor binding efficacy results. The reference compounds had diverse receptor binding patterns, with EEG responses dominated by EEG-delta wave frequencies. In contrast, the receptor binding pattern of the EOs was remarkably consistent and replicated a subclinical affinity pattern corresponding to the inhibitory glycine-α-GLRA3 and dopamine-D2 receptors, producing responses dominated by EEG-alpha wave frequencies. The results support the hypothesis that EOs stimulate neuroactivity by modulating patterns of neurotransmission affecting alpha wave EEG responses.

Does timing of phytonutrient intake influence the suppression of postprandial oxidative stress? A systematic literature review.

BACKGROUND: Postprandial oxidative stress markers in blood are generated transiently from various tissues and cells following high-fat and/or high-carbohydrate (HFHC) meals, and may be suppressed by certain phytonutrients, such as polyphenols and carotenoids. However, the transient presence of phytonutrients in circulation suggests that timing of consumption, relative to the meal, could be important. This systematic review investigates the effect of timing of phytonutrient intake on blood markers of postprandial oxidative processes. METHOD: EMBASE, Medline, Scopus and Web of Science were searched up to December 2020. Eligible studies met the criteria: 1) healthy human adults; 2) phytonutrient(s) consumed in solid form within 24 h of a HFHC meal; 3) postprandial measurements of oxidative stress or antioxidants in blood; and 4) controlled study design. Cohen's d effect sizes were calculated to compare studies. RESULTS: Nine studies, involving 256 participants, were included. Phytonutrients were consumed either at the same time, 1 h before, or the day (>12 h) before a HFHC meal. Significant decreases in blood markers - plasma lipid hydroperoxides, plasma malondialdehyde, serum sNox2-dp, serum 8-iso-PGF2α, platelet p47phox phosphorylation, and Keap-1 and p47phox protein levels in mononuclear cells (MNCs) - were observed where the phytonutrient was consumed together with the challenge meal (n = 4). Lack of any effect on oxidative stress markers was observed where phytonutrients were consumed with (n = 1), 1 h before (n = 1), and the day before (n = 2) the HFHC meal. CONCLUSION: Phytonutrients consumed with a HFHC meal significantly suppressed some markers of oxidative stress in blood. Although there were only a limited number of studies, it appears that suppression appeared effective at the time of peak phytonutrient concentration in plasma. However, further studies are required to confirm the observations and systematically optimise the effect of timing.

Anxiolytic effects of essential oils may involve anti-oxidant regulation of the pro-oxidant effects of ascorbate in the brain.

Essential oils (EOs) absorbed via inhalation are consistently reported to produce anxiolytic effects. The underlying neurochemical mechanisms, however, are not well understood. High concentrations of ascorbate in the human brain (~10 mM in neurons) implicates this compound as a key signaling molecule and regulator of oxidative stress. In this study, we demonstrate the significant in vitro capacity of ascorbate to produce H2O2 in the presence of oxygen at physiological pH values, peaking at ~400 µM for ascorbate levels of 1.0 mg/mL (5.6 mM). In comparison, individual EOs and selected neurotransmitters at similar concentrations produced <100 µM H2O2. Systematic studies with binary and ternary mixtures containing ascorbate indicated that EOs and neurotransmitters could variably enhance (pro-oxidant, POX) or suppress (anti-oxidant, AOX) the production of H2O2 versus the ascorbate control, depending on the concentration ratios of the components in the mixture. Moreover, the AOX/POX chemistry observed with binary mixtures did not necessarily predict effects with ternary mixtures, where the POX ascorbate chemistry tended to dominate. A model is proposed to account for the ability of compounds with electron-donating capacity to catalytically regenerate ascorbate from intermediate oxidized forms of ascorbate, thus driving H2O2 production and exerting a net POX effect; whilst compounds that irreversibly reacted with oxidized forms of ascorbate suppressed the production of H2O2 and produced an overall AOX effect. Since the anxiolytic effects of different EOs, including extracts of Lavendula angustifolia (lavender) and Salvia rosmarinus (rosemary), were associated with AOX regulation of H2O2 production by ascorbate, it can be concluded that these anxiolytic effects are potentially related to the AOX properties of EOs. In contrast, EOs driving POX effects (eg, Junipenus communis (Juniper) berry EO) are proposed to be more useful for their potential anti-microbial or cancer cytotoxic applications.

The role of microbial infection in the pathogenesis of Alzheimer's disease and the opportunity for protection by anti-microbial peptides.

Alzheimer's disease (AD) is the most common cause of dementia. Its pathology is primarily characterized by extracellular deposits of amyloid ß peptide and intracellular neurofibrillary tangles. Current rationales to explain the pathogenesis of AD include amyloid cascade, inflammation, infection defense and anti-microbial protection hypotheses. This review focuses on recent advances in the infection hypothesis, in particular on those pathogenic microbes that act systemically, via periodontal and gastro-intestinal infection routes. It is proposed that the evidence convincingly supports that pathogenic microbial infection is associated with, and is likely a causative trigger for, AD pathology. Microbes can drive AD pathology by two main pathways: either by directly infecting the brain and stimulating amyloid-mediated defence (causative trigger) or indirectly, by stimulating the pro-inflammatory effects of infection. In this context, it follows that anti-microbial/anti-infection therapies could be effective for regulating the pathology and symptoms of AD, depending on the stage of disease. As long-term administration of traditional antibiotic therapy is not recommended, alternative antibiotic agents such as anti-microbial peptides (AMPs), could be preferred for intervention and disease management of AD.

Production of hydrogen peroxide in formulated beverages is associated with the presence of ascorbic acid combined with selected redox-active functional ingredients.

Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that mediates essential signaling in vivo but may cause irreversible tissue damage under dysregulated or acute exposure conditions. Beverages containing redox-active compounds might produce H2O2 during shelf storage and potentially be consumed. Concentrations of H2O2 in selected 'functional' (including energy, E, n = 28), 'non-functional' flavored, (S, n = 6) and mineral water (W, n = 6) drinks were measured under ambient (i.e., produced in situ) and 'potentiated' conditions (i.e., H2O2 production enhanced by addition of a reducing agent, to simulate availability of reducible substrates in vivo). Under air-saturated conditions, mean H2O2 contents were: 15.60 ± 15.84; 1.39 ± 2.06 and 0.30 ± 0.21 µM in E, S and W drinks, respectively. Under air-saturated, potentiated conditions, mean rates of H2O2 production were 21.7 ± 33.3, 0.98 ± 2.84, and -0.38 ± 1.18 µM/h for E, S and W drinks, respectively. Using multivariate statistics, the ingredient significantly associated with H2O2 production in combination with other ingredients was found to be ascorbic acid.

Exploring user empowerment and service improvement within an Irish epilepsy service using Checkland's 'Soft Systems' approach.

AIM: To illustrate the value of Checkland's 'Soft Systems' approach to explore and analyse the interaction of human and organisational factors that affect service delivery and patient experience in one specialist epilepsy service. BACKGROUND: Checkland's approach is underutilized in relation to health service improvement. One epilepsy service in Ireland is used as an example to illustrate the value of his approach to improve service delivery, particularly when what needs to change is not clear. METHOD: Checkland's 'Soft Systems' seven-stage approach was used collaboratively to explore patients' and clinicians' experience of service delivery and how to improve it. RESULTS: The research identified the practice of empowerment affected the quality of the service experience. Checkland's concept of a human activity system was particularly pertinent in identifying this issue and providing a 'map' for change. CONCLUSION: Wider inferences for the use of Checkland's approach by nurse managers are discussed, as is the value of using Checkland's approach to improve services. IMPLICATIONS FOR NURSING MANAGEMENT: Checkland's 'Soft Systems' is an underutilized approach in health care that could be used by managers to initiate and embed change within a health care service.

The Use of Augmented Reality to Raise Awareness of the Differences Between Osteoarthritis and Rheumatoid Arthritis.

Arthritis is one of the most common disease states worldwide but is still publicly misunderstood and lacks engaging public awareness materials. Within the UK, the most prevalent types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). The two are commonly mistaken as the same disease but, in fact, have very different pathogenesis, symptoms and treatments. This chapter describes a study which aimed to assess whether an augmented reality (AR) application could be used to raise awareness about the difference between OA and RA.An application was created for Android tablets that included labelled 3D models, animations and AR scenes triggered from a poster. In total 11 adult participants tested the application taking part in a pretest and posttest which aim to measure the usability of the application and the acquisition of knowledge on OA and RA. A T-test was performed to assess the effectiveness of the application from the pretest and posttest questionnaire outcomes. Overall results were encouraging reporting a very significant acquisition of knowledge and a highly satisfactory user experience.

Understanding the Brain and Exploring the Effects of Clinical Fatigue: From a Patient's Perspective.

Rheumatic and musculoskeletal diseases are a group of devastating autoimmune disorders that all share a common debilitating symptom fatigue. Fatigue is not widely understood and is often underrepresented in treatment regimes. Fatigue is the least successfully managed symptom of these conditions; however, it can often be the one of the greatest impairments.Augmented reality (AR) enhances a person's reality showing a hybrid environment where real and virtual objects coexist. Currently educational AR applications are saturating the application market, as they have shown great potential for increasing comprehension and understanding of complex concepts. AR expands user engagement by enhancing the learner's enjoyment and enriching their learning environment.This research explores the development and subsequent effect of an AR application on education around fatigue and basic neuroanatomy within the general population. The application was created using medical scan dataset, a variety of 3D modelling software and a game engine to create a functional and interactive augmented application. The application explores the effects of fatigue on a person's daily life while also laying a foundation of basic neuroanatomy. A pilot test conducted on 14 participants (8 males, 5 females and 1 other), with ages ranged 16-64 (4 form range 16 to 24, 5 from range 25 to 34, 1 from range 35 to 44, 3 from range 45 to 54, 1 from 55 to 64), shows the application is highly usable, increases understanding of basic neuroanatomical concepts and has the potential to improve understanding of fatigue. Nonetheless, further development and testing of the application are imperative so that we can gain a better understanding of the usability of the application with wider audiences. Future developments will aim to further aid knowledge acquisition and enhance understanding of fatigue, a complex and widely misunderstood concept.

Characterising absorption and health-related properties of phytochemicals extracted from Malaysian palm fruit biomass after oil extraction.

After oil extraction, palm fruit biomass contains abundant water-soluble phytochemicals (PCs) with proven bioactivity in regulating oxidative stress and inflammation (OSI). For optimal bioefficacy following oral consumption, the pharmacokinetic plasma peak (Tmax) should be bio-matched with the onset of OSI, which can be predicted from the Phytochemical Absorption Prediction (PCAP) model and methodology. Predicted absorption and potential for regulation of OSI by measures of total phenolic content, antioxidant capacity and hydrogen peroxide production capacity, were applied to characterise eight extracts from mesocarp fibre and kernel shells of oil-depleted palm fruits. Results indicated post-consumption absorption Tmax ranges of 0.5-12 h and 2-6 h for intake in liquid and solid forms, respectively, and generally high antioxidant activity of the extracts. The research supports that PC extracts of palm fruit biomass have broad potential uses for human health as dietary antioxidants in foods, supplements or functional beverages.

Exploring Dimensions of Empowerment from the Patients' Perspective in One Specialist Epilepsy Service in Ireland.

Empowerment is integral to patient-centered practice, particularly as this relates to people with chronic conditions, though operationally it is poorly understood in this context. Empowerment, therefore, as experienced by patients with a chronic condition needs exploration. This article reports the experience of empowerment by patients in one specialist epilepsy service in Ireland as an exemplar of broader issues affecting empowerment of patients with chronic conditions. A Frameworks Approach was used to analyze in-depth interviews with patients (n = 10) in one Irish epilepsy service. Analysis was further informed by nonparticipatory observation of service delivery. Results indicate that patients' negative experiences of empowerment appear to be derived from traditional social norms relating to clinician patient power dimensions and social stigma internalized by clinicians at an unconscious level. With this in mind, educational approaches based upon critical social theory may provide a framework and guide to enable services to engage with these issues and embrace empowerment of patients with chronic conditions within therapeutic engagement.

Dose-related effects of inhaled essential oils on behavioural measures of anxiety and depression and biomarkers of oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential oils (EOs) are extracts of organic, volatile metabolites of plants that are typically oily liquids at ambient temperatures. Inhalation of EOs can regulate brain health and functions associated with mood and neurodegeneration, reflecting their bioavailability to brain. The aim was to identify physicochemical properties that influenced EO volatility and pathways of brain uptake by inhalation. MATERIALS AND METHODS: Dose-dependency of effects, determined as: total EO intake (µg/g bodyweight-BW), and rate of EO intake (µg/hr/g-BW), was determined by meta-analysis of data from animal studies (10 studies, 12 EOs), measuring effects on anxiety, depression and selected biomarkers of oxidative stress and inflammation (OSI). RESULTS: Results demonstrated benefits on animal behavior at EO intakes of 1-100 µg/g BW and 1-10 µg/hr/g BW (Elevated Plus Maze and Forced Swimming tests) and <100 µg/g BW and 10-100 g/hr/g BW (Marble Burying). EOs regulated OSI biomarkers at intakes of 10-100 µg/g BW and 1-10 µg/h/g BW, and a dose-dependent elevation of dopamine at >1000 µg/g BW and 100-1000 µg/hr/g BW. CONCLUSION: The results support that EO 'aromatherapy' can promote dose-dependent regulation of anxiety, depression and OSI and that efficacy requires optimization of dose.

Retrospective Evaluation of Cycled Resin in Viral Clearance Studies-A Multiple Company Collaboration.

The BioPhorum Development Group Viral Clearance Workstream performed a collaborative retrospective analysis to evaluate packed bed chromatographic resin performance after repeated cycling for two commonly used chromatography steps in biopharmaceutical manufacturing: protein A and anion exchange. Key variables evaluated in the assessment included virus type, resin type, number of reuse cycles, and virus challenge. In this retrospective analysis of viral clearance data on naïve versus cycled resin, powered by the availability of a decade's worth of accumulated industry data, clearance capability was not negatively impacted by resin cycling. This finding is consistent with publications showing that surrogates for viral clearance capabilities could be employed in lieu of testing the viral clearance of cycled resins for protein A and anion exchange chromatography. The rigorous analysis of the retrospective data supports the view that viral clearance studies for cycled resins are not necessary provided that appropriate cleaning methods are applied during repeated use of the chromatography columns.LAY ABSTRACT: The manufacturing processes for biopharmaceutical products often include reusable chromatographic resins that remove process- and product-related impurities as well as potential contaminating viruses. Typically, chromatography resin is "cycled" through repeated steps of resin conditioning, product purification, and resin cleaning. The cycling approach has been evaluated in both small- and full-scale studies that show the performance parameters are maintained. The ability to remove virus is demonstrated separately in a focused small-scale virus-spiking study that is resource-intensive and costly. This paper is a retrospective review of industry data comparing virus removal by naïve and repeatedly cycled resins that summarizes the viral clearance impact of re-using protein A and anion exchange chromatography resins. The key variables evaluated in the assessment included virus type, resin type, number of cycles, and virus challenge. In this retrospective analysis, it was found that the viral clearance capability is not negatively impacted by resin cycling. This finding is consistent with other publications and supports the view that viral clearance studies for cycled resins are not necessary if appropriate cleaning methods are applied during the repeated use of the chromatography columns.Abbreviations: AAV-2, Adeno-associated virus; A-MuLV, Amphotropic murine leukemia virus; AEX, Anion-exchange chromatography; B/E, Bind and elute; BVDV, Bovine viral diarrhea virus; C.P.G., Controlled pore glass; DEAE, Diethylaminoethanol; EMCV, Encephalomyocarditis virus; FT, Flow through; HAV, Hepatitis A virus; HSV-1, Herpes simplex virus type 1; LOD, Limit of detection; LOQ, Limit of quantification; LRF, Log10 reduction factor; mAb, Monoclonal antibody; MVM, Minute virus of mice; NaOH, Sodium hydroxide; PA, Protein A; PPV, Porcine parvovirus; QA, Quaternary amine; QP, Quaternized polyethyleneimine; qPCR, Quantitative polymerase chain reaction; Reo3, Reovirus type 3; SuHV-1, Suid herpesvirus; SV40, Simian virus 40; X-MuLV, Xenotropic murine leukemia virus.