Open-Label Taste-Testing Study to Evaluate the Acceptability of Both Strawberry-Flavored and Orange-Flavored Amylmetacresol/2,4-Dichlorobenzyl Alcohol Throat Lozenges in Healthy Children

BACKGROUND: Acute sore throat (pharyngitis) is one of the most common illnesses for which children are seen by primary care physicians. Most cases are caused by viruses and are benign and self-limiting. Clinically proven, over-the-counter throat lozenges provide rapid and effective relief of acute sore throat symptoms, and are increasingly important in self-management of this condition. OBJECTIVE: The purpose of this study (International Standard Randomized Controlled Trial Number: ISRCTN34958871) was to evaluate the acceptability of two licensed, commercially available sore throat lozenges containing amylmetacresol and 2,4-dichlorobenzyl (AMC/DCBA)—one strawberry flavored and the other orange flavored—in healthy children. STUDY DESIGN: This was an open-label, single-dose, crossover, taste-testing study in children recruited via a clinical database and advertisements over a 3.5-week period. SETTING: Potentially eligible participants were invited to attend the taste-testing session at a clinic. PARTICIPANTS: At the screening session, which took place either before or on the day of taste testing, details of relevant medical history, medication, and demographics were recorded. Of the 108 screened subjects, 102 were recruited. These were healthy male and female children aged 6–12 years. INTERVENTION: Each child cleansed their palate with water and water biscuits before tasting a strawberry-flavored lozenge (Strepsils(®) strawberry sugar free, Reckitt Benckiser Healthcare Limited, Nottingham, UK; PL 00063/0395), which was sucked for 1 minute and then expelled. The orange-flavored lozenge (Strepsils(®) orange with vitamin C, Reckitt Benckiser Healthcare Limited, Nottingham, UK; PL 016242152) was tasted at least 15 minutes later following further cleansing of the palate. The spontaneous reaction of the child on tasting each lozenge was observed and recorded. Subjects were asked to indicate their liking for each lozenge, using a 7-point hedonic facial scale, and were required to answer a series of questions relating to what they liked and disliked about the taste and the feel of the lozenge in the mouth and throat. The primary endpoint was the proportion of subjects with a hedonic facial score of >4. Secondary endpoints included the spontaneous reaction of the child on tasting the lozenge and responses to questions related to taste. RESULTS: The taste of the lozenge was scored >4 (i.e. ‘good’, ‘really good’, or ‘super good’) by 85.3 % of subjects for the strawberry flavor and 49.0 % for the orange flavor (p < 0.0001). The mean (standard deviation) score was 5.72 (1) for the strawberry-flavored lozenge and 4.35 (2) for the orange-flavored lozenge. The proportion of subjects willing to take the lozenge again was 94 % for the strawberry flavor and 56 % for the orange flavor. CONCLUSIONS: Strawberry-flavored AMC/DCBA lozenges were liked by, and acceptable to, the majority of the children. AMC/DCBA orange-flavored lozenges were also liked by, and acceptable to, approximately half the children. Overall, both strawberry and orange would be suitable flavors for lozenges intended for children when they suffer from sore throat

Investigating heparin affinity chromatography for extracellular vesicle purification and fractionation

The purification of extracellular vesicles (EVs) remains a major hurdle in the progression of fundamental research and the commercial application of EV-based products. In this study, we evaluated the potential of heparin affinity chromatography (HAC) to purify neural stem cell-derived EVs as part of a multistep process. Bind-elute chromatography, such as HAC, is an attractive method of purification because it is highly scalable, robust and can be automated. Our findings support an interaction between EVs and heparin. The recovery of EVs using HAC based on particle counts was a minimum of 68.7%. We found HAC could remove on average 98.8% and 99.0% of residual protein and DNA respectively. In addition to EV purification, HAC was used to separate EVs into three populations based on their affinity to the heparin column. Within these populations, we detected differences in the expression of the exosome-associated protein TSG101 and the tetraspanin immunophenotype. However, the significance of these observations is not clear. Overall HAC shows promise as a potential purification method to capture EVs and this study proposes a novel application of HAC for EV fractionation. Moving forward, a better understanding of the heparin-EV interaction would be required before HAC can be more widely adopted for these applications

BCL-3 promotes a cancer stem cell phenotype by enhancing β-catenin signalling in colorectal tumour cells

To decrease bowel cancer incidence and improve survival, we need to understand the mechanisms that drive tumorigenesis. Recently, B-cell lymphoma 3 (BCL-3; a key regulator of NF-κB signalling) has been recognised as an important oncogenic player in solid tumours. Although reported to be overexpressed in a subset of colorectal cancers (CRCs), the role of BCL-3 expression in colorectal tumorigenesis remains poorly understood. Despite evidence in the literature that BCL-3 may interact with β-catenin, it is perhaps surprising, given the importance of deregulated Wnt/β-catenin/T-cell factor (TCF) signalling in colorectal carcinogenesis, that the functional significance of this interaction is not known. Here, we show for the first time that BCL-3 acts as a co-activator of β-catenin/TCF-mediated transcriptional activity in CRC cell lines and that this interaction is important for Wnt-regulated intestinal stem cell gene expression. We demonstrate that targeting BCL-3 expression (using RNA interference) reduced β-catenin/TCF-dependent transcription and the expression of intestinal stem cell genes LGR5 and ASCL2. In contrast, the expression of canonical Wnt targets Myc and cyclin D1 remained unchanged. Furthermore, we show that BCL-3 increases the functional stem cell phenotype, as shown by colorectal spheroid and tumoursphere formation in 3D culture conditions. We propose that BCL-3 acts as a driver of the stem cell phenotype in CRC cells, potentially promoting tumour cell plasticity and therapeutic resistance. As recent reports highlight the limitations of directly targeting cancer stem cells (CSCs), we believe that identifying and targeting drivers of stem cell plasticity have significant potential as new therapeutic targets. This article has an associated First Person interview with the first author of the paper

Determinants of participation in a web-based health risk assessment and consequences for health promotion programs

Background: The health risk assessment (HRA) is a type of health promotion program frequently offered at the workplace. Insight into the underlying determinants of participation is needed to evaluate and implement these interventions. Objective: To analyze whether individual characteristics including demographics, health behavior, self-rated health, and work-related factors are associated with participation and nonparticipation in a Web-based HRA. Methods: Determinants of participation and nonparticipation were investigated in a cross-sectional study among individuals employed at five Dutch organizations. Multivariate logistic regression was performed to identify determinants of participation and nonparticipation in the HRA after controlling for organization and all other variables. Results: Of the 8431 employees who were invited, 31.9% (2686/8431) enrolled in the HRA. The online questionnaire was completed by 27.2% (1564/5745) of the nonparticipants. Determinants of participation were some periods of stress at home or work in the preceding year (OR 1.62, 95% CI 1.08-2.42), a decreasing number of weekdays on which at least 30 minutes were spent on moderate to vigorous physical activity (ORdayPA0.84, 95% CI 0.79-0.90), and increasing alcohol consumption. Determinants of nonparticipation were less-than-positive self-rated health (poor/very poor vs very good, OR 0.25, 95% CI 0.08-0.81) and tobacco use (at least weekly vs none, OR 0.65, 95% CI 0.46-0.90). Conclusions: This study showed that with regard to isolated health behaviors (insufficient physical activity, excess alcohol consumption, and stress), those who could benefit most from the HRA were more likely to participate. However, tobacco users and those who rate

Neutrophil-derived miR-223 as local biomarker of bacterial peritonitis

Infection remains a major cause of morbidity, mortality and technique failure in patients with end stage kidney failure who receive peritoneal dialysis (PD). Recent research suggests that the early inflammatory response at the site of infection carries diagnostically relevant information, suggesting that organ and pathogen-specific “immune fingerprints” may guide targeted treatment decisions and allow patient stratification and risk prediction at the point of care. Here, we recorded microRNA profiles in the PD effluent of patients presenting with symptoms of acute peritonitis and show that elevated peritoneal miR-223 and reduced miR-31 levels were useful predictors of bacterial infection. Cell culture experiments indicated that miR-223 was predominantly produced by infiltrating immune cells (neutrophils, monocytes), while miR-31 was mainly derived from the local tissue (mesothelial cells, fibroblasts). miR-223 was found to be functionally stabilised in PD effluent from peritonitis patients, with a proportion likely to be incorporated into neutrophil-derived exosomes. Our study demonstrates that microRNAs are useful biomarkers of bacterial infection in PD-related peritonitis and have the potential to contribute to disease-specific immune fingerprints. Exosome-encapsulated microRNAs may have a functional role in intercellular communication between immune cells responding to the infection and the local tissue, to help clear the infection, resolve the inflammation and restore homeostasis

Hypothalamic inflammation is reversed by endurance training in anorectic-cachectic rats

<p>Abstract</p> <p>Aim</p> <p>We tested the effects of a cancer cachexia-anorexia sydrome upon the balance of anti and pro-inflammatory cytokines in the hypothalamus of sedentary or trained tumour-bearing (Walker-256 carcinosarcoma) rats.</p> <p>Methods</p> <p>Animals were randomly assigned to a sedentary control (SC), sedentary tumour-bearing (ST), and sedentary pair-fed (SPF) groups or, exercised control (EC), exercised tumour-bearing (ET) and exercised pair-fed (EPF) groups. Trained rats ran on a treadmill (60%VO_2max) for 60 min/d, 5 days/wk, for 8 wks. We evaluated food intake, leptin and cytokine (TNF-α, IL1β) levels in the hypothalamus.</p> <p>Results</p> <p>The cumulative food intake and serum leptin concentration were reduced in ST compared to SC. Leptin gene expression in the retroperitoneal adipose tissue (RPAT) was increased in SPF in comparison with SC and ST, and in the mesenteric adipose tissue (MEAT) the same parameter was decreased in ST in relation to SC. Leptin levels in RPAT and MEAT were decreased in ST, when compared with SC. Exercise training was also able to reduce tumour weight when compared to ST group. In the hypothalamus, IL-1β and IL-10 gene expression was higher in ST than in SC and SPF. Cytokine concentration in hypothalamus was higher in ST (TNF-α and IL-1β, p < 0.05), compared with SC and SPF. These pro-inflammatory cytokines concentrations were restored to control values (p < 0.05), when the animals were submitted to endurance training.</p> <p>Conclusion</p> <p>Cancer-induced anorexia leads towards a pro-inflammatory state in the hypothalamus, which is prevented by endurance training which induces an anti-inflammatory state, with concomitant decrease of tumour weight.</p

International Society of Sports Nutrition Position Stand: Probiotics.

Position statement: The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the mechanisms and use of probiotic supplementation to optimize the health, performance, and recovery of athletes. Based on the current available literature, the conclusions of the ISSN are as follows: 1)Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (FAO/WHO).2)Probiotic administration has been linked to a multitude of health benefits, with gut and immune health being the most researched applications.3)Despite the existence of shared, core mechanisms for probiotic function, health benefits of probiotics are strain- and dose-dependent.4)Athletes have varying gut microbiota compositions that appear to reflect the activity level of the host in comparison to sedentary people, with the differences linked primarily to the volume of exercise and amount of protein consumption. Whether differences in gut microbiota composition affect probiotic efficacy is unknown.5)The main function of the gut is to digest food and absorb nutrients. In athletic populations, certain probiotics strains can increase absorption of key nutrients such as amino acids from protein, and affect the pharmacology and physiological properties of multiple food components.6)Immune depression in athletes worsens with excessive training load, psychological stress, disturbed sleep, and environmental extremes, all of which can contribute to an increased risk of respiratory tract infections. In certain situations, including exposure to crowds, foreign travel and poor hygiene at home, and training or competition venues, athletes' exposure to pathogens may be elevated leading to increased rates of infections. Approximately 70% of the immune system is located in the gut and probiotic supplementation has been shown to promote a healthy immune response. In an athletic population, specific probiotic strains can reduce the number of episodes, severity and duration of upper respiratory tract infections.7)Intense, prolonged exercise, especially in the heat, has been shown to increase gut permeability which potentially can result in systemic toxemia. Specific probiotic strains can improve the integrity of the gut-barrier function in athletes.8)Administration of selected anti-inflammatory probiotic strains have been linked to improved recovery from muscle-damaging exercise.9)The minimal effective dose and method of administration (potency per serving, single vs. split dose, delivery form) of a specific probiotic strain depends on validation studies for this particular strain. Products that contain probiotics must include the genus, species, and strain of each live microorganism on its label as well as the total estimated quantity of each probiotic strain at the end of the product's shelf life, as measured by colony forming units (CFU) or live cells.10)Preclinical and early human research has shown potential probiotic benefits relevant to an athletic population that include improved body composition and lean body mass, normalizing age-related declines in testosterone levels, reductions in cortisol levels indicating improved responses to a physical or mental stressor, reduction of exercise-induced lactate, and increased neurotransmitter synthesis, cognition and mood. However, these potential benefits require validation in more rigorous human studies and in an athletic population

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Prostate cancer exosomes as modulators of the tumor microenvironment

Researchers are currently trying to understand why some men with prostate cancer go on to develop aggressive disease whilst others maintain slow growing tumors. Although endogenous genetic anomalies within the tumor cell are important, the prevailing view is that the tissue microenvironment as a whole is the determinant factor. Many studies have focussed on the role of soluble factors in modulating the nature of the tumor microenvironment. There is however a growing interest in the role of extracellular vesicles, including exosomes, as regulators of disease progression. A variety of resident cells, as well as infiltrating cells, all contribute to a heterogeneous population of exosomes within the tumor microenvironment. Studies focussing on the role of exosomes in prostate cancer are however relatively rare. In this review, evidence from various cancers, including prostate, is used to present numerous potential roles of exosomes in prostate cancer. Whilst further validation of some functions may remain necessary it is clear that exosomes play a major role in intercellular communication between various cell types within the tumor microenvironment and are necessary for driving disease progression