Comparative bio-accessibility, bioavailability and bioequivalence of quercetin, apigenin, glucoraphanin and carotenoids from freeze-dried vegetables incorporated into a baked snack versus minimally processed vegetables:Evidence from in vitro models and a human bioavailability study

The aim was to incorporate vegetables containing the phytochemicals quercetin, apigenin, glucoraphanin and carotenoids into a processed potato-based snack and assess their bioaccessibility and bioavailability. Three different processing routes were tested for incorporation and retention of phytochemicals in snacks using individually quick frozen or freeze-dried vegetables. No significant differences in the uptake or transport of quercetin or apigenin between a vegetable mix or snacks were observed using the CaCo-2 transwell model. Simulated in vitro digestions predicted a substantial release of quercetin and apigenin, some release of glucoraphanin but none for carotenes from either the snack or equivalent steamed vegetables. In humans, there were no significant differences in the bioavailability of quercetin, apigenin or glucoraphanin from the snack or equivalent steamed vegetables. We have shown that significant quantities of freeze-dried vegetables can be incorporated into snacks with good retention of phytochemicals and with similar bioavailability to equivalent steamed vegetables

Activin receptor-like kinase receptors ALK5 and ALK1 are both required for TGFβ-induced chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells

Introduction Bone marrow-derived mesenchymal stem cells (BMSCs) are promising for cartilage regeneration because BMSCs can differentiate into cartilage tissue-producing chondrocytes. Transforming Growth Factor beta; (TGFbeta;) is crucial for inducing chondrogenic differentiation of BMSCs and is known to signal via Activin receptor-Like Kinase (ALK) receptors ALK5 and ALK1. Since the specific role of these two TGFbeta; receptors in chondrogenesis is unknown, we investigated whether ALK5 and ALK1 are expressed in BMSCs and whether both receptors are required for chondrogenic differentiation of BMSCs. Materials & Methods ALK5 and ALK1 gene expression in human BMSCs was determined with RT-qPCR. To induce chondrogenesis, human BMSCs were pellet-cultured in serum-free chondrogenic medium containing TGFβ1. Chondrogenesis was evaluated by aggrecan and collagen type IIα1 RT-qPCR analysis, and histological stainings of proteoglycans and collagen type II. To overexpress constitutively active (ca) receptors, BMSCs were transduced either with caALK5 or caALK1. Expression of ALK5 and ALK1 was downregulated by transducing BMSCs with shRNA against ALK5 or ALK1. Results ALK5 and ALK1 were expressed in in vitro-expanded as well as in pellet-cultured BMSCs from five donors, but mRNA levels of both TGFbeta; receptors did not clearly associate with chondrogenic induction. TGFbeta; increased ALK5 and decreased ALK1 gene expression in chondrogenically differentiating BMSC pellets. Neither caALK5 nor caALK1 overexpression induced cartilage matrix formation as efficient as that induced by TGFbeta;. Moreover, short hairpin-mediated downregulation of either ALK5 or ALK1 resulted in a strong inhibition of TGFbeta;-induced chondrogenesis. Conclusion ALK5 as well as ALK1 are required for TGFbeta;-induced chondrogenic differentiation of BMSCs, and TGFbeta; not only directly induces chondrogenesis, but also modulates ALK5 and ALK1 receptor signaling in BMSCs. These results imply that optimizing cartilage formation by mesenchymal stem cells will depend on activation of both receptors

Lack of acute or chronic effects of epicatechin-rich and procyanidin-rich apple extracts on blood pressure and cardiometabolic biomarkers in adults with moderately elevated blood pressure: a randomized, placebo-controlled crossover trial

Background: The reported effects of flavanol-rich foods such as cocoa, dark chocolate, and apples on blood pressure and endothelial function may be due to the monomeric flavanols [mainly (–)-epicatechin (EC)], the oligomeric flavanols [procyanidins (PCs)], or other components. Reports of well-controlled intervention studies that test the effects of isolated oligomeric flavanols on biomarkers of cardiovascular health are lacking. Objective: We studied the acute and chronic effects of an EC-rich apple flavanol extract and isolated apple PCs on systolic blood pressure (BP) and other cardiometabolic biomarkers. Design: Forty-two healthy men and women with moderately elevated BP completed this randomized, double-blind, placebo-controlled, 4-arm crossover trial. Participants ingested a single dose of an apple flavanol extract (70 mg monomeric flavanols, 65 mg PCs), a double dose of this extract (140 mg monomeric flavanols, 130 mg PCs), an apple PC extract (130 mg PCs, 6.5 mg monomeric flavanols), or placebo capsules once daily for 4 wk, in random order. Biomarkers of cardiovascular disease risk and vascular function were measured before and 2 h after ingestion of the first dose and after the 4-wk intervention. Results: Compared with placebo, none of the isolated flavanol treatments significantly (P < 0.05) changed systolic or diastolic BP (peripheral and aortic), plasma nitric oxide (NO) reaction products, or measures of arterial stiffness (carotid femoral pulse-wave velocity, brachial-ankle pulse-wave velocity, or Augmentation Index) after 2 h or 4 wk of the intervention. There were no changes in plasma endogenous metabolite profiles or circulating NO; endothelin 1; total, HDL, or LDL cholesterol; triglycerides; fasting glucose; fructosamine; or insulin after 4 wk of the intervention. Conclusions: Our data suggest that, in isolation, neither monomeric flavanols nor PCs affect BP, blood lipid profiles, endothelial function, or glucose control in individuals with moderately elevated BP. The reported benefits of consuming flavanol-rich cocoa, chocolate, and apple products appear to be dependent on other components, which may work in combination with monomeric flavanols and PCs. This trial was registered at www.clinicaltrials.gov as NCT02013856

Meta-Analysis of the Effects of Foods and Derived Products Containing Ellagitannins and Anthocyanins on Cardiometabolic Biomarkers: Analysis of Factors Influencing Variability of the Individual Responses

peer-reviewedUnderstanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers. The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored. Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes. Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts. Additionally, we found an indication of a small increase in HDL-cholesterol most significant with nuts and, in flow-mediated dilation by nuts and berries. Most of these effects were detected in obese/overweight people but we found limited or non-evidence in normoweight individuals or of the influence of sex or smoking status. The effects of other factors, i.e., habitual diet, health status or country where the study was conducted, were inconsistent and require further investigation.This article is based upon work from COST Action FA1403—POSITIVe “Interindividual variation in response to consumption of plant food bioactives and determinants involved” supported by COST (European Cooperation in Science and Technology, http://www.cost.eu/). The authors thank the financial support of the COST Action FA1403 “POSITIVe” to conduct a short-term scientific mission to K.C. at CEBAS-CSIC (A.G.-S. and M.T.G.-C.) during which the data analysis was performed

Dynamic Regulation of TWIST1 Expression during Chondrogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells

Human bone marrow-derived mesenchymal stem cells (BMSCs) are clinically promising to repair damaged articular cartilage. This study investigated TWIST1, an important transcriptional regulator in mesenchymal lineages, in BMSC chondrogenesis. We hypothesized that downregulation of TWIST1 expression is required for in vitro chondrogenic differentiation. Indeed, significant downregulation of TWIST1 was observed in murine skeletal progenitor cells during limb development (_N_ = 3 embryos), and during chondrogenic differentiation of culture-expanded human articular chondrocytes (_N_ = 3 donors) and isolated adult human BMSCs (_N_ = 7 donors), consistent with an inhibitory effect of TWIST1 expression on chondrogenic differentiation. Silencing of TWIST1 expression in BMSCs by siRNA, however, did not improve chondrogenic differentiation potential. Interestingly, additional investigation revealed that downregulation of TWIST1 in chondrogenic BMSCs is preceded by an initial upregulation. Similar upregulation is observed in non-chondrogenic BMSCs (_N_ = 5 donors); however, non-chondrogenic cells fail to downregulate TWIST1 expression thereafter, preventing their chondrogenic differentiation. This study describes for the first time endogenous TWIST1 expression during in vitro chondrogenic differentiation of human BMSCs, demonstrating dynamic regulation of TWIST1 expression whereby upregulation and then downregulation of TWIST1 expression are required for chondrogenic differentiation of BMSCs. Elucidation of the molecular regulation of, and by, TWIST1 will provide targets for optimization of BMSC chondrogenic differentiation culture

Narrative Substrates: Reifying and Managing Emergent Narratives in Persistent Game Worlds

International audiencePlayers in modern Massively Multiplayer Online Role-Playing Games progress through ambitiously designed narratives, but have no real influence on the game, since only their characters' data, not the game environment, persists. Although earlier games supported player influence by persisting changes in the world, they relied on players' capacity to form their own stories and lacked guidance for character progression. We explore how persistence and narrative emergence let us build upon players' influence rather than restrict it. We ran four studies and found that players highly value first-time and unique events, and often externalize their experiences to the Web to collaborate and socialize, but unintentionally also disrupt some aspects of in-game play. We introduce Narrative Substrates, a theoretical framework for designing game architec-tures that represent, manage, and persist traces of player activity as unique, interactive content. To illustrate and test the theory, we developed the game We Ride and deployed it as a two-phase technology probe over one year. We identify key benefits and challenges of our approach, and argue that reification of emergent narratives offers new design opportunities for creating truly interactive games

Immunogenicity Is Not Improved by Increased Antigen Dose or Booster Dosing of Seasonal Influenza Vaccine in a Randomized Trial of HIV Infected Adults

The risk of poor vaccine immunogenicity and more severe influenza disease in HIV necessitate strategies to improve vaccine efficacy.A randomized, multi-centered, controlled, vaccine trial with three parallel groups was conducted at 12 CIHR Canadian HIV Trials Network sites. Three dosing strategies were used in HIV infected adults (18 to 60 years): two standard doses over 28 days, two double doses over 28 days and a single standard dose of influenza vaccine, administered prior to the 2008 influenza season. A trivalent killed split non-adjuvanted influenza vaccine (Fluviral™) was used. Serum hemagglutinin inhibition (HAI) activity for the three influenza strains in the vaccine was measured to assess immunogenicity.297 of 298 participants received at least one injection. Baseline CD4 (median 470 cells/µL) and HIV RNA (76% of patients with viral load <50 copies/mL) were similar between groups. 89% were on HAART. The overall immunogenicity of influenza vaccine across time points and the three influenza strains assessed was poor (Range HAI ≥ 40 =  31-58%). Double dose plus double dose booster slightly increased the proportion achieving HAI titre doubling from baseline for A/Brisbane and B/Florida at weeks 4, 8 and 20 compared to standard vaccine dose. Increased immunogenicity with increased antigen dose and booster dosing was most apparent in participants with unsuppressed HIV RNA at baseline. None of 8 serious adverse events were thought to be immunization-related.Even with increased antigen dose and booster dosing, non-adjuvanted influenza vaccine immunogenicity is poor in HIV infected individuals. Alternative influenza vaccines are required in this hyporesponsive population.ClinicalTrials.gov NCT00764998

Self-management of a musculoskeletal condition for people from harder to reach groups: a qualitative patient interview study.

This article has been accepted for publication in Disability and Rehabilitation, published by Taylor & FrancisBackground: This study recorded the functional health literacy levels of people with musculoskeletal (MSK) conditions from harder to reach groups and explored their experiences in engaging with health care professionals to self-manage their MSK condition.Methods: We recruited participants, identified by key health and social care contacts as likely to have lower health literacy levels, and used semi-structured interviews to collect data. Thematic analysis was used to identify the main key themes arising from the transcribed interviews.Results: Eighteen participants were identified and recruited from harder to reach community populations, 10 were scored as having inadequate functional health literacy on the Short Form Rapid Estimate of Adult Literacy Measure. Three themes were identified in relation to participants' experiences of MSK self-management approaches: engaging with health care services; interpreting the health care providers' message; and facilitating participation in MSK self-management.Conclusions: Our findings indicate that people with a MSK condition, from harder to reach groups, experience multi-morbidity, find health care systems complicated and hear from health care professionals that their MSK condition cannot be cured. People interpreted that a lack of cure meant that nothing could be done to help their MSK pain. Engaging with self-management strategies was not seen as a priority for our participants. Strategies to simplify health communication, more time to process health information and supportive social networks helped our participants to understand and manage their MSK health on a day-to-day basis. Implications for RehabilitationMSK conditions are long term and prevalent in the UK with substantial impact on people's daily life.Currently self-management strategies for MSK conditions are poorly communicated and many patients believe that nothing can be done to help their MSK pain.Good clinician communication that supports self-management is needed so that key messages can be effectively understood and used by patients with a range of literacy skills.Health services need to be even more accessible to help all individuals from a range of backgrounds better self-manage their MSK conditions.This work was funded by Arthritis Research UK [Grant ref 19623)]

Urinary excretion of strawberry anthocyanins is dose dependent for physiological oral doses of fresh fruit

There is considerable interest in coloured fruits and berries as sources of biologically active anthocyanins. To examine the relationship between the oral dose and the amount excreted for anthocyanins from a food source across a physiological range of doses, volunteers were fed, in random order, four portions (100–400 g) of fresh strawberries as part of a standard breakfast. Urine was collected at 2 h intervals up to 8 h, and for the period 8–24 h. Fresh strawberries contained pelargonidin-3-glucoside as the major anthocyanin with smaller amounts of cyanidin-3-glucoside and pelargonidin-3-rutinoside. Anthocyanins were detected in the urine of all volunteers for all doses, predominantly as pelargonidin glucuronide and sulphate metabolites. There was a strong, linear relationship between oral dose and anthocyanin excretion (Pearson's product moment correlation coefficient = 0.692, p < 0.001, n = 40) which indicated that on an average, every additional unit of dose caused 0.0166 units of excretion. Within individuals, dose – excretion data fitted a linear regression model (median R2 = 0.93). We conclude that strawberry anthocyanins are partially bioavailable in humans with a linear relationship between oral dose and urinary excretion for doses up to 400 g fresh fruit

Telehealth Palliative Care Needs Rounds During a Pandemic

Older people living in care homes deserve access to specialist palliative care in their last months of life, and this has never been more important than during a global pandemic. Palliative Care Needs Rounds facilitated by nurse practitioners are cost-effective, reduce avoidable hospital transfers, improve quality of death and dying, and increase the capacity of staff to recognize and plan for care for dying residents in care homes. Conducting Palliative Care Needs Rounds via telehealth increases access to specialist palliative care while reducing the risk of coronavirus disease 2019 transmission