Natural Choline from Egg Yolk Phospholipids Is More Efficiently Absorbed Compared with Choline Bitartrate; Outcomes of A Randomized Trial in Healthy Adults

Choline is a vitamin-like essential nutrient, important throughout one’s lifespan. Therefore, choline salts are added to infant formula, supplements and functional foods. However, if choline is present in a natural form, e.g. bound to phospholipids, it may be more efficiently absorbed. The study’s aim was to evaluate if choline uptake is improved after consumption of an egg yolk phospholipid drink, containing 3 g of phospholipid bound choline, compared to a control drink with 3 g of choline bitartrate. We performed a randomized, double blind, cross-over trial with 18 participants. Plasma choline, betaine and dimethylglycine concentrations were determined before and up to six hours after consumption of the drinks. The plasma choline response, as determined by the incremental area under the curve, was four times higher after consumption of the egg yolk phospholipid drink compared with the control drink (p < 0.01). Similar outcomes were also observed for choline’s main metabolites, betaine (p < 0.01) and dimethylglycine (p = 0.01). Consumption of natural choline from egg yolk phospholipids improved choline absorption compared to consumption of chemically produced choline bitartrate. This information is of relevance for the food industry, instead of adding choline-salts, adding choline from egg yolk phospholipids can improve choline uptake and positively impact health

A framework for conceptualising early intervention for eating disorders

OBJECTIVE: This paper outlines the evidence base for early intervention for eating disorders; provides a global overview of how early intervention for eating disorders is provided in different regions and settings; and proposes policy, service, clinician and research recommendations to progress early intervention for eating disorders. METHOD AND RESULTS: Currently, access to eating disorder treatment often takes many years or does not occur at all. This is despite neurobiological, clinical and socioeconomic evidence showing that early intervention may improve outcomes and facilitate full sustained recovery from an eating disorder. There is also considerable variation worldwide in how eating disorder care is provided, with marked inequalities in treatment provision. Despite these barriers, there are existing evidence-based approaches to early intervention for eating disorders and progress is being made in scaling these. CONCLUSIONS: We propose action steps for the field that will transform eating disorder service provision and facilitate early detection, treatment and recovery for everyone affected by eating disorders, regardless of age, socioeconomic status and personal characteristics

The health outcomes and physical activity in preschoolers (HOPP) study: rationale and design

<p>Abstract</p> <p>Background</p> <p>The early years are the period of growth for which we know the least about the impact of physical activity. In contrast, we know that more than 90 % of school-aged Canadian children, for example, are not meeting physical activity recommendations. Such an activity crisis is a major contributor to recent trends in childhood obesity, to which preschoolers are not immune. The World Health Organization estimated that more than 42 million children under the age of 5 years were overweight world-wide in 2010. If an activity crisis exists during the preschool years, we should also be concerned about its broader impact on health. Unfortunately, the relationship between physical activity and health during the early years is poorly understood. The goal of the Health Outcomes and Physical activity in Preschoolers (HOPP) study is to describe how the prevalence and patterns of physical activity in preschoolers are associated with indices of health.</p> <p>Methods</p> <p>The HOPP study is a prospective cohort study. We aim to recruit 400 3- to 5-year-old children (equal number of boys and girls) and test them once per year for 3 years. Each annual assessment involves 2 laboratory visits and 7 consecutive days of physical activity monitoring with protocols developed in our pilot work. At visit 1, we assess body composition, aerobic fitness, short-term muscle power, motor skills, and have the parents complete a series of questionnaires related to their child’s physical activity, health-related quality of life and general behaviour. Over 7 consecutive days each child wears an accelerometer on his/her waist to objectively monitor physical activity. The accelerometer is programmed to record movement every 3 s, which is needed to accurately capture the intensity of physical activity. At visit 2, we assess vascular structure and function using ultrasound. To assess the associations between physical activity and health outcomes, our primary analysis will involve mixed-effects models for longitudinal analyses.</p> <p>Discussion</p> <p>The HOPP study addresses a significant gap in health research and our findings will hold the potential to shape public health policy for active living during the early years.</p

Neuronal Conduction of Excitation without Action Potentials Based on Ceramide Production

International audienceBACKGROUND: Action potentials are the classic mechanism by which neurons convey a state of excitation throughout their length, leading, after synaptic transmission, to the activation of other neurons and consequently to network functioning. Using an in vitro integrated model, we found previously that peripheral networks in the autonomic nervous system can organise an unconventional regulatory reflex of the digestive tract motility without action potentials. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we used combined neuropharmacological and biochemical approaches to elucidate some steps of the mechanism that conveys excitation along the nerves fibres without action potentials. This mechanism requires the production of ceramide in membrane lipid rafts, which triggers in the cytoplasm an increase in intracellular calcium concentration, followed by activation of a neuronal nitric oxide synthase leading to local production of nitric oxide, and then to guanosine cyclic monophosphate. This sequence of second messengers is activated in cascade from rafts to rafts to ensure conduction of the excitation along the nerve fibres. CONCLUSIONS/SIGNIFICANCE: Our results indicate that second messengers are involved in neuronal conduction of excitation without action potentials. This mechanism represents the first evidence-to our knowledge-that excitation is carried along nerves independently of electrical signals. This unexpected ceramide-based conduction of excitation without action potentials along the autonomic nerve fibres opens up new prospects in our understanding of neuronal functioning

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Treatment of children and adolescents with avoidant/restrictive food intake disorder: a case series examining the feasibility of family therapy and adjunctive treatments

Abstract Background To date, little research has examined the effectiveness of either modified Family-Based Therapy or psychopharmacological treatments for patients diagnosed with avoidant/restrictive food intake disorder (ARFID), and there is little evidence to guide clinicians treating children and adolescents with ARFID. This case series describes the clinical presentations, treatments and outcomes of six patient diagnosed with ARFID who were treated sequentially by a child psychiatrist and adolescent medicine physician in a hospital-based eating disorder program.  Case Presentations Five out of six cases were female and median age of patients at assessment was 12.9 (SD = 1.13) years. On average, patients’ percentage of treatment goal weight was 80.5% at initial assessment (SD = 8.56) and 81.9% (SD = 7.08) when family therapy began. Cases 1, 2 and 3 were admitted to a specialized inpatient unit at assessment due to medical instability (2) or failed outpatient treatment (1), and all six cases presented with severe co-morbid anxiety. All patients were treated using a combination of medical monitoring, family therapy, medication (including olanzapine, fluoxetine and in two cases cyproheptadine), and cognitive behavioural therapy. At treatment termination, all six patients had achieved their goal weight. Conclusion These cases illustrate the complex ways in which young patients with ARFID can present, the illness’ effect on development and mental health, and the positive outcomes associated with weight gain and concurrent treatment for co-morbid anxiety disorders

The Research on Eating and Adolescent Lifestyle (REAL) Study Protocol: A Shared Biopsychosocial Model for Predicting Eating Disorders and Obesity in Adolescents

This manuscript describes the rationale, design and methods of the Research on Eating and Adolescent Lifestyles Study (REAL), which from 2006-2013, aimed to test an integrative biopsychosocial model of cross-sectional and longitudinal predictors and developmental mechanisms for both eating disorders (EDs) and obesity in a large sample of Canadian youth. The present study examined predictors from four main areas of risk: biological (e.g. weight status, pubertal stage), environmental (e.g. societal influences), individual (e.g. self-perception), and eating and weight specific behaviors (e.g. disordered eating) to test direct and indirect paths for both ED and obesity simultaneously as outcomes. Participants were recruited based on a convenience sample from 43 urban and rural public schools, and data collection ran from 2006-2013. The cross sectional sample consisted of 3043 males and females in grades 7-12. The longitudinal sample was comprised of 1197 students in grades 7 and 9 who completed annual follow ups for 7 years. The REAL study is unique as it proposes a biopsychosocial model to explain EDs and obesity in adolescents under parallel processes within a single model, and is more integrative and comprehensive than previous models. Findings from this study were intended to inform prevention initiatives and further the understanding of the etiological similarities amongst EDs and obesity in a large sample of both male and female youth across adolescence

The relation between weight-based teasing and psychological adjustment in adolescents

OBJECTIVE: To determine the prevalence of weight-based teasing, and evaluate its association with depression, anxiety and unhealthy eating behaviour in a large sample of adolescents in the Ottawa (Ontario) area. METHODS: A total of 1491 adolescents from public and private middle schools and high schools in rural and urba