Adaptation and Validation of the Well-Being Related to Food Questionnaire (Well-BFQ©) for the French-Speaking General Adult Population of Québec, Canada.

Efforts to develop effective strategies that improve dietary intake are needed; however, this improvement in diet quality must not be at the expense of well-being. The Well-Being related to Food Questionnaire (Well-BFQ©) is a tool that has been developed in France to comprehensively measure food well-being. Even though the same language is spoken in France and in Québec, cultural and linguistic differences are present, which supports the importance of adapting and validating this tool before its use in the Québec population. This study aimed to adapt and validate the Well-BFQ© for the French-speaking general adult population of Québec, Canada. The Well-BFQ© underwent a full linguistic adaptation process, including an expert panel adaptation step, a pretest among 30 French-speaking adult (18-65 years) Quebecers, and a final proofreading. The questionnaire was thereafter administered to 203 French-speaking adult Quebecers (49.3% females, MAGE = 34.9, SD = 13.5; 88.2% Caucasians; 54.2% with a university degree). The exploratory factor analysis showed a two-factor structure: (1) food well-being related to physical and psychological health (27 items) and (2) food well-being related to symbolic/pleasure of food (32 items). Internal consistency was adequate, with a Cronbach's α of 0.92 and 0.93, respectively, for the subscales, and 0.94 for the total scale. The total food well-being score, as well as the two subscale scores, were associated with psychological and eating-related variables in expected directions. Overall, the adapted version of the Well-BFQ© was found to be a valid instrument to measure food well-being in the French-speaking general adult population of Québec, Canada.

Moral injury and well-being in essential workers during the COVID-19 pandemic: local survey findings.

BACKGROUND: Essential workers have faced many difficult situations working during the pandemic. Staff may feel that they, or other people, have acted wrongly and be distressed by this. This represents moral injury, which has been linked with significant mental ill health. METHODS: This survey asked essential workers in County Durham and Darlington about their experiences during the first wave of the pandemic and anything they felt would help. Well-being and moral injury were rated using sliders. RESULTS: There were 566 responses. A majority of respondents reported feeling troubled by other people's actions they felt were wrong (60% scored over 40, where 0 is 'not at all troubled' and 100 'very troubled', median score=52.5). Respondents were generally less troubled by their own actions (median score=3). Well-being and moral injury scores varied by employment sector (eg, National Health Service (NHS) staff were more troubled by the actions of others than non-NHS staff).Staff suggestions included regular supervisor check-ins, ensuring kindness from everyone, fair rules and enforcement and improving communication and processes. Respondents offered simple, practical actions that could be taken by leaders at team, organisation, societal and governmental levels to tackle moral injury and the underlying causes of moral injurious environments. CONCLUSION: Using these findings to develop a strategy to address moral injury is important, not only for staff well-being, but staff retention and continued delivery of vital services in these challenging times. Working together, we can seek to reduce and mitigate 'moral injury' the same way we do for other physical workplace 'injuries'.

Calcitonin-secreting neuroendocrine neoplasms of the lung: a systematic review and narrative synthesis.

Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an ectopic source of calcitonin secretion can represent a complex diagnostic conundrum for managing physicians, with cases of unnecessary thyroidectomy reported in the literature. This manuscript reports a case of ectopic hypercalcitonaemia from a metastatic neuroendocrine neoplasm of the lung with concurrent thyroid pathology and summarises the results of a systematic review of the literature. Medical Literature Analysis and Retrieval System Online, Excerpta Medica, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and SCOPUS databases were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori. The protocol for this systematic review was developed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols, and followed methods outlined in The Cochrane Handbook for Systematic Reviews of Interventions. This systematic review is registered with PROSPERO. It is vital to consider diagnoses other than medullary thyroid carcinoma when presented with a patient with raised calcitonin, as it is not pathognomonic of medullary thyroid carcinoma. Lung neuroendocrine neoplasms can appear similar to medullary thyroid carcinoma histologically, they can secrete calcitonin and metastasize to the thyroid. Patients with medullary thyroid carcinoma may show stimulated calcitonin values over two or more times above the basal values, whereas calcitonin-secreting neuroendocrine neoplasms may or may not show response to stimulation tests. The present review summarises existing evidence from cases of ectopic hypercalcitonaemia to lung neuroendocrine neoplasms.

Real-time continuous glucose monitoring in preterm infants (REACT): an international, open-label, randomised controlled trial.

BACKGROUND: Hyperglycaemia and hypoglycaemia are common in preterm infants and have been associated with increased risk of mortality and morbidity. Interventions to reduce risk associated with these exposures are particularly challenging due to the infrequent measurement of blood glucose concentrations, with the potential of causing more harm instead of improving outcomes for these infants. Continuous glucose monitoring (CGM) is widely used in adults and children with diabetes to improve glucose control, but has not been approved for use in neonates. The REACT trial aimed to evaluate the efficacy and safety of CGM in preterm infants requiring intensive care. METHODS: This international, open-label, randomised controlled trial was done in 13 neonatal intensive care units in the UK, Spain, and the Netherlands. Infants were included if they were within 24 h of birth, had a birthweight of 1200 g or less, had a gestational age up to 33 weeks plus 6 days, and had parental written informed consent. Infants were randomly assigned (1:1) to real-time CGM or standard care (with masked CGM for comparison) using a central web randomisation system, stratified by recruiting centre and gestational age (<26 or ≥26 weeks). The primary efficacy outcome was the proportion of time sensor glucose concentration was 2·6-10 mmol/L for the first week of life. Safety outcomes related to hypoglycaemia (glucose concentrations <2·6 mmol/L) in the first 7 days of life. All outcomes were assessed on the basis of intention to treat in the full analysis set with available data. The study is registered with the International Standard Randomised Control Trials Registry, ISRCTN12793535. FINDINGS: Between July 4, 2016, and Jan 27, 2019, 182 infants were enrolled, 180 of whom were randomly assigned (85 to real-time CGM, 95 to standard care). 70 infants in the real-time CGM intervention group and 85 in the standard care group had CGM data and were included in the primary analysis. Compared with infants in the standard care group, infants managed using CGM had more time in the 2·6-10 mmol/L glucose concentration target range (mean proportion of time 84% [SD 22] vs 94% [11]; adjusted mean difference 8·9% [95% CI 3·4-14·4]), equivalent to 13 h (95% CI 5-21). More infants in the standard care group were exposed to at least one episode of sensor glucose concentration of less than 2·6 mmol/L for more than 1 h than those in the intervention group (13 [15%] of 85 vs four [6%] of 70). There were no serious adverse events related to the use of the device or episodes of infection. INTERPRETATION: Real-time CGM can reduce exposure to prolonged or severe hyperglycaemia and hypoglycaemia. Further studies using CGM are required to determine optimal glucose targets, strategies to obtain them, and the potential effect on long-term health outcomes. FUNDING: National Institute for Health Research Efficacy and Mechanisms Evaluation Programme.

Can eating pleasure be a lever for healthy eating? A systematic scoping review of eating pleasure and its links with dietary behaviors and health.

The aims of this review were to map and summarize data currently available about 1) key dimensions of eating pleasure; 2) associations of eating pleasure, and its key dimensions, with dietary and health outcomes and 3) the most promising intervention strategies using eating pleasure to promote healthy eating. Using the scoping review methodology, a comprehensive search of the peer-reviewed literature (Medline, PsycInfo, Embase, ERIC, Web of Science, CINAHL, ABI/Inform global and Sociology Abstract) and of the grey literature (ProQuest Dissertations & Theses and Google) was carried out by two independent reviewers. We included 119 of the 28,908 studies found. In total, 89 sub-dimensions of eating pleasure were grouped into 22 key dimensions. The most frequently found related to sensory experiences (in 50.9% of the documents), social experiences (42.7%), food characteristics besides sensory attributes (27.3%), food preparation process (19.1%), novelty (16.4%), variety (14.5%), mindful eating (13.6%), visceral eating (12.7%), place where food is consumed (11.8%) and memories associated with eating (10.9%). Forty-five studies, mostly cross-sectional (62.2%), have documented links between eating pleasure and dietary and/or health outcomes. Most studies (57.1%) reported favorable associations between eating pleasure and dietary outcomes. For health outcomes, results were less consistent. The links between eating pleasure and both dietary and health outcomes varied according to the dimensions of eating pleasure studied. Finally, results from 11 independent interventions suggested that strategies focusing on sensory experiences, cooking and/or sharing activities, mindful eating, and positive memories related to healthy food may be most promising. Thus, eating pleasure may be an ally in the promotion of healthy eating. However, systematically developed, evidence-based interventions are needed to better understand how eating pleasure may be a lever for healthy eating.

Impact of pleasure-oriented messages on food choices: is it more effective than traditional health-oriented messages to promote healthy eating?

Some authors have suggested that eating pleasure is underused to promote healthy eating. However, little is known about the potential of pleasure-oriented messages to lead to healthier food choices. The aim of this study was to examine the effects of pleasure- and health-oriented messages on food choices made from a buffet. One hundred and ninety-eight participants (50% women), unaware of the real objective of the study, were randomized in three groups: 1) pleasure, 2) health, and 3) control. They first completed three 24 h food recalls to assess their overall diet quality using the Canadian Healthy Eating Index (C-HEI; score: 0 to 100). Thereafter, participants came to the research institute and those randomized in the "pleasure" and "health" groups read a leaflet on healthy eating, using either a pleasure or a health orientation respectively. Participants in the control group had no leaflet to read. All participants had subsequently to choose four food items in a buffet offering both healthy and unhealthy foods. Results showed a group by diet quality interaction (p = 0.02). Among participants with lower diet quality (C-HEI score below 50), those in the pleasure and health groups were more likely than participants in the control group to choose a healthier main course (prevalence ratios (PR) 1.71, 95% CI 1.12-2.62 and 1.83, 95% CI 1.21-2.77 for the pleasure and health group respectively) and a healthier beverage (PR 1.67, 95% CI 1.02-2.71 and 1.66, 95% CI 1.02-2.72, respectively). No such effect was observed among participants with higher C-HEI scores. In conclusion, our results suggest that in people with sub-optimal dietary habits, pleasure-oriented messages and traditional health messages are both useful to favor healthy main course and beverage choices.

Protocol of a randomised controlled trial of real-time continuous glucose monitoring in neonatal intensive care 'REACT'.

INTRODUCTION: Hyperglycaemia is common in the very preterm infant and has been associated with adverse outcomes. Preventing hyperglycaemia without increasing the risk of hypoglycaemia has proved challenging. The development of real-time continuous glucose monitors (CGM) to inform treatment decisions provides an opportunity to reduce this risk. This study aims to assess the feasibility of CGM combined with a specifically designed paper guideline to target glucose control in the preterm infant. METHODS AND ANALYSES: The Real Time Continuous Glucose Monitoring in Neonatal Intensive Care (REACT) trial is an international multicentre randomised controlled trial. 200 preterm infants ≤1200 g and ≤24 hours of age will be randomly allocated to either real-time CGM or standard care (with blinded CGM data collection). The primary outcome is time in target 2.6-10 mmol/L during the study intervention assessed using CGM. Secondary outcomes include efficacy relating to glucose control, utility including staff acceptability, safety outcomes relating to incidence and prevalence of hypoglycaemia and health economic analyses. ETHICS AND DISSEMINATION: The REACT trial has been approved by the National Health Service Health Research Authority National Research Ethics Service Committee East of England (Cambridge Central); Medical Ethics Review Committee, VU University Medical Centre, Amsterdam, The Netherlands and the Research Ethics Committee, Sant Joan de Déu Research Foundation, Barcelona, Spain. Recruitment began in July 2016 and will continue until mid-2018. The trial has been adopted by the National Institute of Health Research Clinical Research Network portfolio (ID: 18826) and is registered with anInternational Standard Randomised Control Number (ISRCTN registry ID: 12793535). Dissemination plans include presentations at scientific conferences, scientific publications and efforts at stakeholder engagement. TRIAL REGISTRATION NUMBER: ISRCTN12793535; Pre-results.

Frequent Monitoring of C-Peptide Levels in Newly Diagnosed Type 1 Subjects Using Dried Blood Spots Collected at Home.

Objective: To evaluate an approach to measure ß-cell function by frequent testing of C-peptide concentrations in dried blood spots (DBSs). Patients: Thirty-two children, aged 7 to 17 years, with a recent diagnosis of type 1 diabetes. Design: Mixed-meal tolerance test (MMTT) within 6 and again at 12 months after diagnosis, with paired venous and DBS C-peptide sampling at 0 and 90 minutes. Weekly DBS C-peptide before and after standardized breakfasts collected at home. Results: DBS and plasma C-peptide levels (n = 115) correlated strongly (r = 0·91; P < 0.001). The Bland-Altman plot indicated good agreement. The median number of home-collected DBS cards per participant was 24 over a median of 6.9 months. Repeated DBS C-peptide levels varied considerably within and between subjects. Adjustment for corresponding home glucose measurements reduced the variance, permitting accurate description of changes over time. The correlation of the C-peptide slope over time (assessed by repeated home DBS) vs area under the curve during the two MMTTs was r = 0.73 (P < 0.001). Mixed models showed that a 1-month increase in diabetes duration was associated with 17-pmol/L decline in fasting DBS C-peptide, whereas increases of 1 mmol/L in glucose, 1 year older age at diagnosis, and 100 pmol/L higher baseline plasma C-peptide were associated with 18, 17, and 61 pmol/L higher fasting DBS C-peptide levels, respectively. In addition, glucose responsiveness decreased with longer diabetes duration. Conclusion: Our approach permitted frequent assessment of C-peptide, making it feasible to monitor ß-cell function at home. Evaluation of changes in the slope of C-peptide through this method may permit short-term evaluation of promising interventions.

Phyllodes Tumor of the Breast With Malignant Melanoma Component: A Case Report.

Phyllodes tumors of the breast display a wide variation in histological appearance and are classified into benign, borderline, and malignant categories based on a combination of histological parameters. These tumors may include a malignant heterologous component that is believed to originate through a process of multidirectional differentiation from a cancer stem cell. In these cases, the tumor is classified as a malignant phyllodes tumor. Among the heterologous elements that have been described in malignant phyllodes tumors are rhabdomyosarcoma, chondrosarcoma, osteosarcoma, liposarcoma and angiosarcoma. We present the first case of a phyllodes tumor with a malignant melanoma component in the breast of a 71-year-old lady, discussing the clinical implications of this diagnosis.

Effective recruitment of participants to a phase I study using the internet and publicity releases through charities and patient organisations: analysis of the adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D).

BACKGROUND: A barrier to the successful development of new disease treatments is the timely recruitment of participants to experimental medicine studies that are primarily designed to investigate biological mechanisms rather than evaluate clinical efficacy. The aim of this study was to analyse the performance of three recruitment sources and the effect of publicity events during the Adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D). METHODS: The final study outcome, demography, disease duration, residence and the effect of publicity events on the performance of three recruitment sources (clinics, type 1 diabetes (T1D) disease register and the internet) were analysed from a bespoke DILT1D recruitment database. For the internet source, the origin of website hits in relation to publicity events was also evaluated. RESULTS: A total of 735 potentially eligible participants were approached to identify the final 45 DILT1D participants. A total of 477 (64%) were identified via the disease register, but only 59 (12%) responded to contact. A total of 317 individuals registered with the DILT1D study team. Self-referral via the study website generated 170 (54%) registered individuals and was the most popular and successful source, with 88 (28%) sourced from diabetes clinics and 59 (19%) from the disease register. Of those with known T1D duration (N = 272), the internet and clinics sources identified a larger number (57, 21%) of newly diagnosed T1D (<100 days post-diagnosis) compared to the register (1, 0.4%). The internet extended the geographical reach of the study, enabling both national and international participation. Targeted website posts and promotional events from organisations supporting T1D research and treatment during the trial were essential to the success of the internet recruitment strategy. CONCLUSIONS: Analysis of the DILT1D study recruitment outcomes illustrates the utility of an active internet recruitment strategy, supported by patient groups and charities, funding agencies and sponsors, in successfully conducting an early phase study in T1D. This recruitment strategy should now be evaluated in late-stage trials to develop treatments for T1D and other diseases. TRIAL REGISTRATION: NCT01827735 (registered: 4 April 2013); ISRCTN27852285 (registered: 23 March 2013); DRN767 (registered: 21 January 2013).

Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes.

Studies in type 1 diabetes indicate potential disease heterogeneity, notably in the rate of ß-cell loss, responsiveness to immunotherapies, and, in limited studies, islet pathology. We sought evidence for different immunological phenotypes using two approaches. First, we defined blood autoimmune response phenotypes by combinatorial, multiparameter analysis of autoantibodies and autoreactive T-cell responses in 33 children/adolescents with newly diagnosed diabetes. Multidimensional cluster analysis showed two equal-sized patient agglomerations characterized by proinflammatory (interferon-γ-positive, multiautoantibody-positive) and partially regulated (interleukin-10-positive, pauci-autoantibody-positive) responses. Multiautoantibody-positive nondiabetic siblings at high risk of disease progression showed similar clustering. Additionally, pancreas samples obtained post mortem from a separate cohort of 21 children/adolescents with recently diagnosed type 1 diabetes were examined immunohistologically. This revealed two distinct types of insulitic lesions distinguishable by the degree of cellular infiltrate and presence of B cells that we termed "hyper-immune CD20Hi" and "pauci-immune CD20Lo." Of note, subjects had only one infiltration phenotype and were partitioned by this into two equal-sized groups that differed significantly by age at diagnosis, with hyper-immune CD20Hi subjects being 5 years younger. These data indicate potentially related islet and blood autoimmune response phenotypes that coincide with and precede disease. We conclude that different immunopathological processes (endotypes) may underlie type 1 diabetes, carrying important implications for treatment and prevention strategies.

Postthymic expansion in human CD4 naive T cells defined by expression of functional high-affinity IL-2 receptors.

As the thymus involutes with age, the maintenance of peripheral naive T cells in humans becomes strongly dependent on peripheral cell division. However, mechanisms that orchestrate homeostatic division remain unclear. In this study we present evidence that the frequency of naive CD4 T cells that express CD25 (IL-2 receptor α-chain) increases with age on subsets of both CD31(+) and CD31(-) naive CD4 T cells. Analyses of TCR excision circles from sorted subsets indicate that CD25(+) naive CD4 T cells have undergone more rounds of homeostatic proliferation than their CD25(-) counterparts in both the CD31(+) and CD31(-) subsets, indicating that CD25 is a marker of naive CD4 T cells that have preferentially responded to survival signals from self-Ags or cytokines. CD25 expression on CD25(-) naive CD4 T cells can be induced by IL-7 in vitro in the absence of TCR activation. Although CD25(+) naive T cells respond to lower concentrations of IL-2 as compared with their CD25(-) counterparts, IL-2 responsiveness is further increased in CD31(-) naive T cells by their expression of the signaling IL-2 receptor ß-chain CD122, forming with common γ-chain functional high-affinity IL-2 receptors. CD25 plays a role during activation: CD25(+) naive T cells stimulated in an APC-dependent manner were shown to produce increased levels of IL-2 as compared with their CD25(-) counterparts. This study establishes CD25(+) naive CD4 T cells, which are further delineated by CD31 expression, as a major functionally distinct immune cell subset in humans that warrants further characterization in health and disease.

Upregulation of cytokines is detected in the placentas of cattle infected with Neospora caninum and is more marked early in gestation when fetal death is observed.

The protozoan parasite Neospora caninum causes fetal death after experimental infection of pregnant cattle in early gestation, but the fetus survives a similar infection in late gestation. An increase in Th1-type cytokines in the placenta in response to the presence of the parasite has been implicated as a contributory factor to fetal death due to immune-mediated pathological alterations. We measured, using real-time reverse transcription-PCR and enzyme-linked immunosorbent assay, the levels of cytokines in the placentas of cattle experimentally infected with N. caninum in early and late gestation. After infection in early gestation, fetal death occurred, and the levels of mRNA of both Th1 and Th2 cytokines, including interleukin-2 (IL-2), gamma interferon (IFN-gamma), IL-12p40, tumor necrosis factor alpha (TNF-alpha), IL-18, IL-10, and IL-4, were significantly (P < 0.01) increased by up to 1,000-fold. There was extensive placental necrosis and a corresponding infiltration of CD4(+) T cells and macrophages. IFN-gamma protein expression was also highly increased, and a modest increase in transforming growth factor beta was detected. A much smaller increase in the same cytokines and IFN-gamma protein expression, with minimal placental necrosis and inflammatory infiltration, occurred after N. caninum infection in late gestation when the fetuses survived. Comparison of cytokine mRNA levels in separated maternal and fetal placental tissue that showed maternal tissue was the major source of all cytokine mRNA except for IL-10 and TNF-alpha, which were similar in both maternal and fetal tissues. These results suggest that the magnitude of the cytokine response correlates with but is not necessarily the cause of fetal death and demonstrate that a polarized Th1 response was not evident in the placentas of N. caninum-infected cattle.

The extent of parasite-associated necrosis in the placenta and foetal tissues of cattle following Neospora caninum infection in early and late gestation correlates with foetal death.

The protozoan parasite Neospora caninum is the most frequently diagnosed abortifacient in the UK and a leading cause of abortion worldwide but the mechanisms leading to abortion are not fully understood. The distribution of parasites and the histopathological changes in the placenta and foetus were compared in 12 cows following experimental infection of cattle with N. caninum in early (n=6) and late (n=6) gestation, by PCR, immunohistology, light microscopy and transmission electron microscopy. Twelve uninfected pregnant cattle were used as controls. Infection in early gestation led to foetal death. In the placentae of cattle immediately following foetal death, N. caninum DNA was detected and there was evidence of widespread parasite dissemination. This was associated with extensive focal epithelial necrosis, serum leakage and moderate maternal interstitial mononuclear cell infiltration. In the foetuses, parasites were evident in all tissues examined and were associated with necrosis. In the placenta of cattle infected in late gestation, N. caninum DNA was detected sporadically but parasites were not evident immunohistologically. Small foci of necrosis were seen associated with mild interstitial mononuclear cell infiltration. Detection of N. caninum DNA in the foetuses was sporadic and parasites were demonstrated immunohistologically in brain and spinal cord only, with an associated mononuclear cell infiltration. This data is consistent with uncontrolled parasite spread in an immunologically immature foetus and could, via multiparenchymal necrosis of foetal tissues or the widespread necrosis and inflammation observed in the placenta, be the cause of Neospora-associated abortions.